Pharmaceutical Excipient By Hitesh
1.0 Introduction
An excipient is generally a pharmacologically inactive substance used as a carrier for the active ingredients of a medication. In many cases, an "active" substance (such as acetylsalicylic acid) may not be easily administered and absorbed by the human body; in such cases the substance in question may be dissolved into or mixed with an excipient. Excipients are also sometimes used to bulk up formulations that contain very potent active ingredients, to allow for convenient and accurate dosage. In addition to their use in the single-dosage quantity, excipients can be used in the manufacturing process to aid in the handling of the active substance concerned. Depending on the route of administration, and form of medication, different excipients may be used. For oral administration tablets and capsules are used. Suppositories are used for rectal administration.
Often, once an active ingredient has been purified, it cannot stay in purified form for long. In many cases it will denature, fall out of solution, or stick to the sides of the container. To stabilize the active ingredient, excipients are added, ensuring that the active ingredient stays "active", and, just as importantly, stable for a sufficiently long period of time that the shelf-life of the product makes it competitive with other products. Thus, the formulation of excipients in many cases is considered a trade secret.
Pharmaceutical codes require that all ingredients in drugs, as well as their chemical decomposition products, be identified and guaranteed to be safe. For this reason, excipients are only used when absolutely necessary and in the smallest amounts possible.
1.1 Objective:
Excipients are now known to have defined functional roles in pharmaceutical dosage forms
(i) Modulating solubility and bioavailability of the active ingredient(s)
(ii) Enhancing stability of the active ingredient(s) in finished dosage forms
(iii) Helping active ingredients maintain a preferred polymorphic form or conformation
(iv) Maintaining pH and osmolarity of liquid formulations
(v) Acting as antioxidants, emulsifying agents, aerosol propellants, tablet binders, and tablet disintegrants
(vi) Preventing aggregation or dissociation;
(vii) Modulating the immunogenic response of active ingredients (e.g., adjuvants) and many others.
United States Pharmacopeia 28–National Formulary 23 lists 40 functional categories of excipients for pharmaceuticals, and many more are expected as new—and usually increasingly complex—drug-delivery systems emerge and evolve. Approximately 800 excipients are currently used in the marketed pharmaceutical products in the United States. This number is also expected to grow with new therapeutic categories, such as gene therapy and cell therapy, and new drug delivery technologies.
Excipients can themselves affect safety and efficacy outcomes. Excipients, or their impurities, can be associated with adverse events, either by direct action or by formation of undesirable adducts. By modifying absorption and, for parenteral products, distribution, excipients can change exposure patterns and thus influence both safety and efficacy outcomes. Excipients are well known to affect the safety and efficacy profiles of locally acting products. As adjuvants, excipients required for protein and conjugate vaccines play a crucial role in the immunogenic properties of vaccines. ‘‘New excipients’’: These may require careful and, not uncommonly, extensive safety studies, with corresponding careful attention to characterization and specification setting. At present, new excipients in the United States do not undergo separate approval but attain market access frequently via a regulatory process in association with the new drug application process for a dosage form.
According to IP 2007
Any substance added in preparing an official preparation shall be innocuous, shall have no adverse influence in the therapeutic efficacy of the active ingredients and shall not interfere with the tests and assays of the Pharmacopoeia. Care should be taken to ensure that such substances are free from harmful organisms.
2.0 Regulation of Pharmaceutical Excipients:-
The U.S. Food and Drug Administration (FDA) does not have a formal regulatory definition of ‘‘excipient’’; however, recent guidance on nonclinical safety studies for excipients provides some indication of FDA acceptance of excipients as more than fillers. The background section of that guidance states:
In this guidance, the phrase new excipients means any inactive ingredients that are intentionally added to therapeutic and diagnostic products, but that: (i) we believe are not intended to exert therapeutic effects at the intended dosage, although they may act to ‘‘improve product delivery’’ (e.g., enhance absorption or control release of the drug substance); and (ii) are not fully qualified by existing safety data with respect to the currently proposed level of exposure, duration of exposure, or route of administration. Examples of excipients include fillers, extenders, diluents, wetting agents, solvents, emulsifiers, preservatives, flavors, absorption enhancers, sustained-release matrices, and coloring agents (emphasis added).
The Agency set out six criteria for an excipient in an OTC product as follows:
1. The ingredient is listed in an official compendium [e.g., USP/National Formulary (NF)] as a pharmaceutical aid or performed certain physical or technical functions in the final formulations (as will be set forth below).
2. The inactive ingredient is used at a level no higher than reasonably required to achieve its physical or technical function. For example, an antimicrobial excipient ingredient could only be used at a level consistent with preservation of the finished product (not at therapeutic levels), and a sunscreen ingredient could only be used at levels that protected the product from breaking down if the top of the jar was left open, not for protecting the user.
3. It is safe when at levels used as inactive ingredient.
4. If it is a color, it must meet appropriate color additive regulations.
5. It does not interfere with the effectiveness of the product. For example, fluoride toothpastes have to be formulated carefully, as the various fluorides react with certain excipients, rendering the product ineffective.
6. The inactive ingredient does not interfere with suitable tests or assays used to assure the identity, quality, strength, or purity of the finished product.
The FDA then set forth a list of 23 physical or technical functions these excipients perform as follows:
1. Air displacement agents: substances that displace air.
2. Color additives: as defined in Section 201(t) of the Act.
3. Denaturing agents: substances added to alcohol to render it unfit for use as an intoxicating beverage.
4. Dispersing agents: substances that promote even distribution throughout a liquid, gaseous, or solid medium with the formulation of a two-phase system.
5. Emollients: bland, fatty, or oleaginous substances that may be applied locally, particularly to the skin, and also to mucous membranes or abraded tissue.
6. Emulsifiers and emulsifying salts: substances that modify surface tension in the component phase of an emulsion to establish a uniform dispersion or emulsion.
7. Flavors and flavoring adjuncts: substances added to impart or help impart a taste or aroma to a product.
8. Fragrances: substances, extracts, or preparations for fragrance diffusing or imparting an agreeable or attractive odor.
9. Humectants: hygroscopic substances incorporated in a product to promote retention of moisture, including moisture retention agents and antidusting agents.
10. Identifiers: substances incorporated in a product to aid manufacturers to distinguish their products from similar or counterfeit products.
11. Levigating agents: substances that aid in reducing another substance to an extremely fine state of subdivision after that other substance has been made into a paste with some suitable liquid in which it is insoluble; also, nonsolid vehicles used to disperse a solid substance to a paste.
12. Ointment bases: vehicles to permit topical application of active medicinal substances.
13. PH control agents: substances added to change or maintain active acidity or basicity, including buffers, acids, alkalies, and neutralizing agents.
14. Preservatives: substances that are added to preparations to prevent or retard deterioration or degradation in a product; such substances include antifungal agents, antioxidants, antimicrobial agents, mold and rope inhibitors, and agents having the effects listed by the National Academy of Sciences—National Research Council under ‘‘preservatives.’’ For the purpose of this section, ‘‘antioxidant’’ is defined as a substance that inhibits oxidation and is used to prevent rancidity of oils or fats or the deterioration of other materials through oxidative processes, including color changes.
15. Propellants, aerating agents, and gases: gases used to supply force to expel a product or used to reduce the amount of oxygen with the product in packaging.
16. Solvents and vehicles: substances used to dissolve or extract another substance or used as carriers of other substances.
17. Stiffening agents: substances that increase the viscosity of certain pharmaceutical preparations, especially ointments.
18. Suppository bases: pharmaceutical bases those are solid at room temperature but melt at body temperature.
19. Surface-active agents: substances used to modify the surface properties of liquids for a variety of effects. The definition includes solubilizing agents, dispersants, detergents, wetting agents, dehydration enhancers, whipping agents, foaming agents, and defoaming agents.
20. Suspending agents: substances required to overcome agglomeration of the dispersed particles and increase the viscosity of the medium so that the particles settle slowly.
21. Tablet and capsule diluents: inert substances incorporated to increase the bulk, to make the tablet or capsule of practical size.
The FDA looks to several sources to identify these previously reviewed excipients, including food additive or food GRAS status, favorable review by JECFA, inclusion in the USP/NF, or prior review in other new drug applications. These previously used/acceptable excipients are identified in the FDA’s Inactive Ingredient Guide. Inclusion of an ingredient in this guide provides the FDA a reasonable assurance that an ingredient, used within the scope of the usage provided in the guide, will be acceptable. Therefore, regulation of well-known excipients in both OTC and prescription drugs are subject to a reasonably certain set of procedures. However, the lack of an independent review for excipients creates significant issues for companies that wish to use new or novel excipients in their drug products. Lack of any independent review means that there is no formal mechanism for providing indicia of acceptability by regulatory agencies, and this creates uncertainties that reduce incentives to develop and use novel ingredients. Despite this lack of formal review, there has been some movement toward mechanisms to address this problem, but official independent status and review of excipients is not likely or necessarily in the best interests of industry or the regulatory agencies.
3.0 EXCIPIENT INTERACTIONS:-
Excipient interactions are a large part of why medicines work (and sometimes why they do not work in development). They can be either beneficial or detrimental, and can be classified simply as
physical,
chemical, and
Physiological/biopharmaceutical.
Physical interactions do not involve chemical change. The components retain their molecular structure. Chemical interactions, on the other hand, involve chemical reactions; i.e., a different molecule (or molecules) is (are) created. Physiological interactions are the interactions between the excipient(s) and the body fluids.
The significance of excipient interactions can extend well beyond the development of the particular medicinal product. Excipient interactions can have implications for
drug stability,
product manufacture,
drug release (dissolution; both in vitro and in vivo),
therapeutic activity, and
Side effect profile.
3.1 Physical Interactions:-
Physical interactions involving excipients are quite common. However, they are also the most difficult to detect because there is often no convenient chemical ‘‘handle,’’as is usually the case with a chemical interaction. Physical interactions are frequently used in pharmaceutical science, for example, to aid processing and to aid or modify drug dissolution (such as oral modified release) or distribution in the body (such as with the use of a parenteral modified release product). Some of these interactions are deliberately invoked to produce a certain effect. Others are unintended, and it is these interactions that usually cause the problems. When considering physical interactions, particularly the ability to predict them in terms of product stability, differential scanning calorimetry (DSC)
Example of an excipient–excipient interaction that can be used to our advantage is the one between xanthan gum and locust bean gum (carob gum or ceratonia) in the presence of water. This interaction forms the basis of the identification test for Xanthan Gum NF. The interaction creates a much more viscous gel system than can be created using either component alone. This has been used in the formulation of controlled release oral solid dosage forms.
3.2 Chemical Interactions:-
Chemical interactions are almost always detrimental to the product because they usually indicate an incompatibility that gives rise to chemical compounds that would be classified as degradation products under ICH Q3B, thus leading to requirements for quantitation, identification, and ultimately qualification (some form of safety assessment) depending on the level found.
Example: Certain APIs are susceptible to oxidation, e.g., atorvastatin and cytidine nucleoside analogues. Fumed metal oxides (e.g., fumed silica, fumed titania, and fumed zirconia) can promote such oxidation reactions. These reactions are more complex in some ways, and less easy to predict.
3.3 PHYSIOLOGICAL/BIOPHARMACEUTICAL INTERACTIONS:-
All excipients interact in a physiological sense when they are administered as part of the medicine. For example, we can get dilution of the vehicle leading to changes in viscosity or precipitation of the drug, disintegration of a tablet or capsule, activation of a controlled release mechanism, etc. This may be stating the obvious to many, but in many instances this interaction with physiological fluids is not actively considered; although it may be understood or assumed to be occurring. However these physiological interactions are very important for the correct functioning of the product, and it is thus important to understand when other interactions occur and what the physiological impact will be. For example, we consider the physical properties of magnesium stearate as a tablet or capsule lubricant, but, as was discussed in ‘‘Physical Interaction’’ section, it is well documented in the literature that when magnesium stearate is used incorrectly these same physical properties can lead to problems that can impact dissolution, and thus could possibly affect bioavailability.
Example: classic biopharmaceutical incompatibility is the interaction between tetracycline antibiotics and calcium and magnesium ions (30). A complex is formed that is not absorbed from the GIT. This is a well-known interaction, and tetracycline antibiotics usually carry a warning against taking them with certain types of food. But magnesium and calcium salts are quite common excipients, in terms of both the range of formulations containing them and the level of inclusion in those formulations.
5.0 Various e Excipient:-
Different Formulation have different excipient .tablet, capsule etc. have different formulation. Various excipients are as follows:
1. Acidifying Agent:
They are used in liquid preparations to provide acidic medium for product stability. PH modifiers such as acidifying agents are important in pharmaceutical and cosmetic formulations where the active pharmaceutical ingredient requires an acidic environment for stability or therapeutic effectiveness.
Example:
o Anhydrous Citric Acid, Powder, USP
o Citric Acid Monohydrate, Crystalline Powder, USP
o Citric Acid Monohydrate, Granular, USP
o Diluted Hydrochloric Acid, 10 Percent (w/v), NF
o Fumaric Acid, NF
o Hydrochloric Acid, 37 Percent, NF
o Malic Acid, NF
o Phosphoric Acid, NF
o Propionic Acid, NF
o Pyronin Y
o Sulfuric Acid, NF
o Tartaric Acid, Granular, NF
2. Denatured alcohol
It is used as a solvent and as fuel for spirit burners and camping stoves. Because of the diversity of industrial uses for denatured alcohol, hundreds of additives and denaturing methods have been used. The main additive has traditionally been 10% methanol, giving rise to the term "methylated spirit. ther typical additives include isopropyl alcohol, acetone, methyl ethyl ketone, methyl isobutyl ketone, and denatonium. Denatured alcohol provides a solution to permit legitimate use and manufacture of ethanol, whereby cheap ethanol can be made available for non-consumption use without the risk of its being converted for consumption. The process creates an ethanol-containing solution that is not suitable for drinking, but is otherwise similar to ethanol for most purposes. As a result, there is no duty on denatured alcohol in most countries, making it considerably cheaper than pure ethanol. As a consequence, its composition is tightly defined by government regulations that vary between countries.
Formulation:
Completely denatured alcohol must be made in accordance with the following formulation: with every 90 parts by volume of alcohol mix 9.5 parts by volume of wood naphtha or a substitute for wood naphtha [note that methanol is not permissible in place of wood naphtha] and 0.5 parts by volume of crude pyridine, and to the resulting mixture add mineral naphtha (petroleum oil) in the proportion of 3.75 litres to every 1000 litres of the mixture and synthetic organic dyestuff (methyl violet) in the proportion of 1.5 grams to every 1000 litres of the mixture.
Denatured alcohol has a variety of common uses:
* As a fuel for marine and ultra-light camping (backpacking) stoves. It is inexpensive, may be extinguished with water, and can be transported without special containers. However, safety concerns do arise from the near-colourless flame with which alcohol burns. A jellied and dyed form is used in the Sterno brand fuel "Canned Heat", and is meant to be ignited and used in the container.
* To pre-heat the vaporizing tubes on wickless paraffin stove such as a Primus stove
* As a sanding aid, as the alcohol helps to more easily remove excess dust because it does not open the wood grain the way that water does.
* As a mealybug exterminator.
* As a cleaning aid in removing ink stains from upholstery or clothes.
* As a cleaner in daily housekeeping
* To disinfect skin prior to an injection or minor surgery, such as draining a blister (also see rubbing alcohol).
* As an antiseptic for minor wounds.
* As a solvent in shellac and shellac-based products.
* As an excipient in a number of pharmaceutical products for oral and topical use.
* As a less expensive alternative to pure ethanol in preserving biological specimens.
* As a less toxic alternative to methanol in the production of biodiesel fuel. Biodiesel produced using ethanol is properly called fatty acid ethyl ester, whereas biodiesel from methanol is properly referred to as fatty acid methyl ester.[6]
* As a germicide in the removal of fungus from skin and coldsore treatment.
* For maintenance of wicks in kerosene heaters and lamps to remove water contaminants and restore the capillary action of the wick. As a wick cleaner and a kerosene additive, adding approx. 1 teaspoon denatured alcohol per gallon of kerosene.
* As a fuel for older toy steam engines which used a wick-type or vapourising burner.
* For window washing.
3. Alkalizing Agents
pH modifiers such as alkalizing agents are important in pharmaceutical and cosmetic formulations where the active pharmaceutical ingredient requires an alkaline environment for stability or therapeutic effectiveness.
Example:
o Ammonium Carbonate, Powder, NF
o Diethanolamine, NF
o Potassium Hydroxide, Pellets, NF
o Sodium Bicarbonate, Powder, USP, EP, BP, JP
o Sodium Borate, Decahydrate, NF
o Sodium Carbonate, Hydrous, NF
o Sodium Hydroxide, Pellets, NF
o Strong Ammonia Solution, NF
o Zinc Carbonate, USP
4.Antimicrobial or Preservatives:-
A preservative is a naturally occurring or synthetically produced substance that is added to products such as foods, pharmaceuticals, paints, biological samples, wood, etc. to prevent decomposition by microbial growth or by undesirable chemical changes. The ideal preservative for food, pharmaceutical and nutraceutical products is effective at low concentrations against a wide spectrum of microbes, soluble in the formulation, non-toxic and non-sensitizing, stable over a wide range of pH and temperature and inexpensive.
Example:
o Benzalkonium Chloride, NF
o Benzalkonium Chloride Solution, 50 Percent, NF
o Benzethonium Chloride, USP
o Benzoic Acid, Crystal, USP, EP, BP, JP
o Benzoic Acid, Flake, USP, EP, JP
o Benzyl Alcohol, NF
o Butylparaben, NF
o Cetylpyridinium Chloride, Monohydrate, USP
o Chlorobutanol, Anhydrous, NF
o Chlorobutanol, Hydrous, NF
o Ethylparaben, NF
o Methylparaben, NF
o Methylparaben Sodium, NF
5. Antioxidant:-
An antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When the chain reaction occurs in a cell, it can cause damage or death to the cell. Antioxidants terminate these chain reactions by removing free radical intermediates, and inhibit other oxidation reactions. They do this by being oxidized themselves, so antioxidants are often reducing agents such as thiols, ascorbic acid, or polyphenols. Antioxidants are widely used as ingredients in dietary supplements and have been investigated for the prevention of diseases such as cancer, coronary heart disease and even altitude sickness. Although initial studies suggested that antioxidant supplements might promote health, later large clinical trials did not detect any benefit and suggested instead that excess supplementation is harmful. In addition to these uses of natural antioxidants in medicine, these compounds have many industrial uses, such as preservatives in food and cosmetics and preventing the degradation of rubber and gasoline.
Example:
o Ascorbic Acid, USP
o Ascorbyl Palmitate, NF
o Butylated Hydroxyanisole, Flakes, NF
o Butylated Hydroxytoluene, Granular, NF
o Potassium Metabisulfite, Crystal, NF
o Propyl Gallate, NF
o Sodium Metabisulfite, Granular, NF, EP, BP, JP
o Sodium Thiosulfate, Pentahydrate, Crystal, USP, EP, BP, JP
o Vitamin E, 1 mg = 1.1 IU, USP
6. Ointment Bases:-
An ointment is a homogeneous, viscous, semi-solid preparation, most commonly a greasy, thick oil (oil 80% - water 20%) with a high viscosity, that is intended for external application to the skin or mucous membranes. They are used as emollients or for the application of active ingredients to the skin for protective, therapeutic, or prophylactic purposes and where a degree of occlusion is desired.Ointments are used topically on a variety of body surfaces. These include the skin and the mucous membranes of the eye (an eye ointment), vagina, anus, and nose. An ointment may or may not be medicated.
The vehicle of an ointment is known as the ointment base. The choice of a base depends upon the clinical indication for the ointment. The different types of ointment bases are:
o Hydrocarbon bases, e.g. hard paraffin, soft paraffin, microcrystalline wax and ceresine
o Absorption bases, e.g. wool fat, beeswax
o Water soluble bases, e.g. macrogols 200, 300, 400
o Emulsifying bases, e.g. emulsifying wax, cetrimide
o Vegetable oils, e.g. olive oil, coconut oil, sesame oil, almond oil and peanut oil.
The medicaments are dispersed in the base, and later they get divided after the drug penetration into the living cells of skin.Ointments are formulated using hydrophobic, hydrophilic, or water-emulsifying bases to provide preparations that are immiscible, miscible, or emulsifiable with skin secretions. They can also be derived from hydrocarbon (fatty), absorption, water-removable, or water-soluble bases.
Example:
Lanolin, USP
Petrolatum, Yellow, USP
Squalane, NF
White Petrolatum, White, USP
7. Suppository Bases:-
Suppository bases are used in the manufacture of suppositories (for rectal administration) and pessaries (for vaginal administration). They can be hydrophobic or hydrophilic. Suppositories should melt at just below body temperature (37° C), which allows for erosion of the dosage form and release of the API. Hard fat suppository bases melt at approximately body temperature. Hydrophilic suppository bases also melt at body temperature, and typically also dissolve or disperse in aqueous media. This allows release to take place via a combination of erosion and dissolution.
Example:
o Cocoa Butter, NF
o Polyethylene Glycol 1000, NF
o Polyethylene Glycol 8000, NF
o Polyethylene Glycol 4500, NF
o Polyethylene Glycol 300, NF
o Polyethylene Glycol 400, NF
o olyethylene Glycol 600, NF
8. Binders:-
When pharmaceutical ingredients cannot be directly compressed to form a tablet, wet granulation must be used. Binders facilitate agglomeration of powder into granules in this process. They are typically dissolved or dispersed in the granulation fluid (usually water or alcohol), or blended dry with the other formulation components before the granulation fluid is added. After initial pelletting, the liquid is evaporated and the binders serve to maintain the resulting dry granules in the appropriate size. They might also affect granule properties such as flow, handling, strength, solubility, compaction, or drug release.
Example:-
o Acacia, Milled Powder, NF
o Acacia, Spray-Dried Powder, NF
o Alginic Acid, NF
o Corn Starch, Powder, NF
o Ethylcellulose, NF
o Gelatin, Powder, NF
o Guar Gum, NF Hypromellose, Substitution Type 2208, 100,000 mPa.s, USP
o Hypromellose, Substitution Type 2208, 100,000 mPa.s, USP
9. Buffering Agents:-
A buffering agent is a weak acid or base used to maintain the acidity (pH) of a solution at a chosen value. The function of a buffering agent is to prevent a rapid change in pH when acids or bases are added to the solution. Buffering agents have variable properties—some are more soluble than others; some are acidic while others are basic. Buffer concentrations are generally between 0.01 and 0.1 M. Formulators select buffers depending on their suitability for use in oral liquids, the stability of the formulation in the presence of the buffer, and compatibility of the buffer with the product container. A buffering agent can be either a weak acid or weak base. Buffering agents are usually added to water to form a buffer solution, which maintains a stable pH in spite of other acids and bases being combined with it. For example, buffered aspirin has a buffering agent, such as MgO, that will maintain the pH of the aspirin as it passes through the acidic stomach of the patient. Another use of a buffering agent is in an antacid tablet, whose primary purpose is to lower the acidity of the stomach.
Example:
o Ammonium Carbonate, Powder, NF
o Ammonium Phosphate, Granular, NF
o Anhydrous Citric Acid, Powder, USP
o Boric Acid, Crystal, NF
o Boric Acid, Granular, NF, EP, BP, JP
o Boric Acid, Powder, NF
o Citric Acid Monohydrate, Crystalline Powder, USP
o Citric Acid Monohydrate, Granular, USP
o Dibasic Potassium Phosphate, Anhydrous, USP, EP, BP
o Lactic Acid, Racemic, USP
o MES, Hemisodium Salt, Biological Buffer
o MOPS Hemisodium Salt, Biological Buffer
10. Chelating Agents:-
Chelation therapy is the use of chelating agents to detoxify poisonous metal agents such as mercury, arsenic, and lead by converting them to a chemically inert form that can be excreted without further interaction with the body.
Example:
o Edetate Calcium Disodium, Hydrate, USP
o Edetate Disodium, Dihydrate, USP
o Edetic Acid, NF
11. Coating Agents
Coating agents are used to form a protective layer over inflamed mucous membranes and skin and to promote more rapid resolution of inflammatory processes. They include starch, aluminum hydroxide, white clay, magnesium trisilicate, and flaxseed. Coating agents are tasteless and disguise the flavor of substances with which they are mixed. Their presence in the intestinal tract diminishes the effect of irritants and delays the absorption of water, food, and medicinal substances. Coating agents also prolong the local effects of medicinal substances on the intestinal tract.
Coating agents are used to treat inflammations of the mucosa of the oral cavity, throat, and gastrointestinal tract and to treat poisoning by irritants and caustic substances. They are also used in mixtures to avoid the irritant side effects of certain medicines and to prolong the duration of local action of various substances.
The ingredients of coating agents include finely ground powders that are highly adsorptive. This property enables these substances to be used in cases of poisoning to limit the absorption of toxins, for example, in poisoning by many salts of alkaloids and heavy metals. Coating agents in the form of powders are also used in the treatment of skin diseases.
Example:
o Ethylcellulose, NF
o Gelatin, Powder, NF
o Hydroxypropyl Cellulose, 4,000-6,500 cps, NF
o Hydroxypropyl Cellulose, 150-400 cps, NF
o Hydroxypropyl Cellulose, 75-100 cps, NF
o Hypromellose, Substitution Type 2208, 100,000 mPa.s, USP
12. Color Agents
Coloring agents produce a distinctive appearance that may serve to differentiate a particular formulation from others that have a similar physical appearance. These substances are subdivided into dyes, inorganic pigments and natural colorants. Coloring agents are subject to federal regulations, and consequently the current regulatory status of a given substance must be determined before its use.Used to impart color to liquid solid tablet and capsule preparations.
Example:
o Caramel, Color, NF
o D and C Green No. 5
o D and C Green No. 6
o D and C Green No. 8
o D and C Orange No. 4
o D and C Red No. 17
o D and C Red No. 22
o D and C Red No. 28
o D and C Red No. 4
o D and C Red No. 6
o D and C Red No. 33
o D and C Violet No. 2
o D and C Yellow No. 11
o D and C Yellow No. 8
o D and C Yellow No. 10
o FD and C Black Shade
o FD and C Blue No. 1
o FD and C Blue No. 2
o FD and C Carmine
o FD and C Emerald Green
o FD and C Green No. 3
o FD and C Red No. 3
o FD and C Red No. 40
o FD and C Yellow No. 5
o FD and C Yellow No. 6
13. Diluents:-
Diluents, sometimes called fillers, increase dosage form, volume, or weight of a pharmaceutical product. Because most dosages require only very small quantities of Active Pharmaceutical Ingredients (APIs), diluents often comprise a significant proportion of the dosage form. This means their physical and chemical properties are key variables in the manufacturing and performance of the product, and should be clearly understood and tightly controlled.
Diluents are also very important in the pharmaceutical industry. They are inactive ingredients that are added to tablets and capsules in addition to the active drug. For example, a Tylenol 325 mg tablet does not weigh 325 mg. This is the weight of the active acetaminophen, while the tablet weighs more due to other additives known as diluents. These additives may be used as binders, disintegrants (help the tablet break apart in the digestive system), or flavor enhancers. Some very common diluents in tablets include starch, cellulose derivatives, and magnesium stearate (a lubricant).
Example:-
o Anhydrous Dibasic Calcium Phosphate, Powder, USP
o Anhydrous Lactose, NF
o Calcium Carbonate, Heavy Powder, USP
o Calcium Carbonate, Light Powder, USP
o Calcium Sulfate, Dihydrate, NF
o Corn Starch, Powder, NF
o Dextrates, Hydrated, NF
o Fructose, Granular, USP
o Kaolin, Powder, USP
o Lactose, Monohydrate, Powder, NF
o Lactose, Monohydrate, Spray-Dried Powder, NF
o Maltitol Solution, NF
14. Disintegrants:-
Disintegrants expand and dissolve when wet causing the tablet to break apart in the digestive tract, releasing the active ingredients for absorption. Disintegrants are agents added to tablet (and some encapsulated) formulations to promote the breakup of the tablet (and capsule “slugs”) into smaller fragments in an aqueous environment, thereby increasing the available surface area and promoting a more rapid release of the drug substance. They ensure that when the tablet is in contact with water, it rapidly breaks down into smaller fragments, facilitating dissolution.
Example:-
o Alginic Acid, NF
o Corn Starch, Powder, NF
o Croscarmellose Sodium, NF
o Microcrystalline Cellulose, NF
o Sodium Starch Glycolate, pH 5.5-7.5, Type A, NF
15. Emulsifying Agents:-
An emulsion is a mixture of two or more immiscible (unblendable) liquids. An emulsifying is a substance which stabilizes an emulsion. In pharmaceutics, hairstyling, personal hygiene and cosmetics, emulsions are frequently used and are usually oil and water emulsions.
'USED TO PROMOTE AND MAINTAIN DISPERSION OF FINELY SUBDIVIDED PARTICLES IN A LIQUID VECHICLE IN WHICH IT IS IMMISCIBLE'
Example:
o Acacia, Milled Powder, NF
o Acacia, Spray-Dried Powder, NF
o Carbomer 940, NF
o Carbomer 941, NF
o Carbomer 1342, NF
o Carbomer 934, Resin, Powder, NF
o Carbomer 934P, Resin, NF
o Cholesterol, NF
o Diethanolamine, NF
o Emulsifying Wax, NF
16. Flavor Agents:-
Flavoring agents alter the sensory impression of a substance mainly by the chemical senses of taste and smell. Of the chemical senses, smell is the main determinant of a food item's flavor.
Example:-
o Almond Oil, Sweet, NF
o Benzaldehyde, NF
o DL-Menthol, Crystal, USP
o Ethyl Acetate, NF
o Ethyl Vanillin, NF
o L-Menthol, Crystal, USP
o Methyl Salicylate, NF
17. Glidants:-
A glidant is a substance that is added to a powder to improve its flowability. A glidant will only work at a certain range of concentrations. Above a certain concentration, the glidant will in fact function to inhibit flowability (Which means that there's a critical concentration to be used if increasing powder's flowability is intended with respect to the glidant and the powder properties). In tablet manufacture, glidants are usually added just prior to compression.
Mechanism Of Action:A Glidant's effect is due to a counter-action to factors resulting in poor flowability of powders. For instance, correcting surface irregularity, reducing interparticular friction & decreasing surface charge. The result is a decrease in the angle of repose which is an indication of an enhanced powder's flowability.
Example:
o Calcium Silicate, NF
o Colloidal Silicon Dioxide, NF, EP
o Talc, Powder, USP
18. Humectants:-
Humectants are while used in pharmaceutical packaging, they most often found within the pharmaceutical formulation itself, where humectants control the moisture content of the pharmaceutical dosage form. Humectants are also used in topical dosage forms to increase the solubility of the active ingredient, to elevate its skin penetration and increase its activity time. Humectants also elevate the hydration of the skin to minimize the dehydrating effect of some active ingredients like corticoids. Examples of humectants include propylene glycol (E1520), glyceryl triacetate (E1518), vinyl alcohol and neoagarobiose. Others can be sugar polyols such as glycerol, sorbitol (E420), xylitol and maltitol (E965), polymeric polyols like polydextrose (E1200), or natural extracts like quillaia (E999), lactic acid, or urea.
19. Lubricants:-
Lubricant excipients decrease friction between the pharmaceutical or nutraceutical preparation’s particles and the tableting equipment contact surfaces.A lubricant is a substance introduced to reduce friction between moving surfaces. It may also have the function of transporting foreign particles. The property of reducing friction is known as lubricity.
A good lubricant possesses the following characteristics:
o High boiling point.
o Low freezing point.
o High viscosity index.
o Thermal stability.
o Corrosion prevention.
o High resistance to oxidation.
Example:
o Calcium Silicate, NF
o Calcium Stearate, NF
o Colloidal Silicon Dioxide, NF, EP
o Magnesium Stearate, NF, BP, JP
o Polyethylene Glycol 8000, NF
o Polyethylene Glycol 4500, NF
o Polyoxyl 40 Stearate, NF
o Polysorbate 20, NF
o Polysorbate 40, NF
20. Plasticizers:-
Plasticizers (UK = plasticisers) or dispersants are additives that increase the plasticity or fluidity of a material. The dominant applications are for plastics, especially polyvinyl chloride (PVC).Selection of the appropriate excipient plasticizer will provide the desired flexibility and permeability on the finished film coating. Properly plasticized films provide both physical and environmental protection to the coated product in transport and storage. Some plasticizer excipients are effective in retarding drug release in acid media, making them an excellent choice for enteric protection.
Example:
o Castor Oil, USP
o Diethyl Phthalate, NF
o Glycerin, Natural, USP, EP, BP, JP
o Glycerin, Synthetic, USP, EP, BP, JP
o Polyethylene Glycol 1000, NF
o Polyethylene Glycol 8000, NF
o Polyethylene Glycol 4500, NF
o Polyethylene Glycol 300, NF
o Polyethylene Glycol 400, NF
o Polyethylene Glycol 600, NF
o Polyethylene Glycol 1500, NF
o Polyethylene Glycol 1450, NF
o Polyethylene Glycol 3350, NF
o Propylene Glycol, USP
o Triacetin, USP
o Triethyl Citrate, FCC
21. Solvents:-
Solvents are used in hundreds of pharmaceutical products. Ointments and other topical products, such as antibacterial creams and corticosteroids, often use solvents in the beginning of the process to manufacture the active ingredients. As the drug is being transformed into its final form, whether cream, lotion or liquid, solvents are used as a medium for blending materials. Solvents also are used to help the final product achieve the proper consistency.
Example:-
o Alcohol, 190 Proof, USP
o Benzyl Benzoate, USP
o Butyl Alcohol, NF
o Corn Oil, NF
o Cottonseed Oil, NF
o Dehydrated Alcohol, 200 Proof, Undenatured, USP
o Ethyl Alcohol, MultiPharm, 200 Proof, EP, JP, USP
o Glycerin, Natural, USP, EP, BP, JP
o Glycerin, Synthetic, USP, EP, BP, JP
o Isopropyl Alcohol, 70 Percent, USP
o Isopropyl Alcohol, 99 Percent, USP, EP, BP, JP
o Light Mineral Oil, NF
22. Stiffening agents:-
They are used primarily in topical preparations for increasing the preparation viscosity. Often stiffening agents find application as sustained-release carriers and to minimize sweating and bleeding of oil-wax blends.
Example:-
o Cetyl Alcohol, NF
o Cetyl Esters Wax, Synthetic, NF
o Emulsifying Wax, NF
o Paraffin, NF
o Stearyl Alcohol, NF
o White Wax, Cake, NF
23. Suspending / Thickening Agents:-
In a pharmaceutical or cosmetic suspension, a suspending agent helps the active ingredient stay in the body of the suspension thereby preventing caking at the bottom. One of the properties of a well-formulated suspension is that it can be easily re-suspended by the use of moderate agitation.
Example:-
o Acacia, Milled Powder, NF
o Acacia, Spray-Dried Powder, NF
o Agar, Flake, NF
o Agar, Granular, NF
o Agar, Powder, NF
o Alginic Acid, NF
o Aluminum Monostearate, NF
o Bentonite, Powder, NF
o Carbomer 940, NF
o Carbomer 941, NF
o Carbomer 1342, NF
24. Sweetening Agents:-
Sweetening agents are substances that sweeten food, beverages, medications, etc., such as sugar, saccharine or other low-calorie synthetic products Sweeteners are added to make the ingredients more palatable, especially in chewable tablets such as antacid or liquids like cough syrup. Sugar can be used to mask unpleasant tastes or smells.
Example:-
o Aspartame, Powder, NF
o Dextrates, Hydrated, NF
o Dextrose, Anhydrous, Granular, USP, EP, BP, JP
o Dextrose, Hydrous, Powder, USP
o Fructose, Granular, USP
o Maltitol Solution, NF
o Mannitol, Powder, USP
o Saccharin Calcium, Crystal, USP
o Saccharin, Powder, NF
o Saccharin Sodium, Dihydrate, Granular, USP
o Sorbitol, Powder, NF
o Sorbitol Solution, 70 Percent, US
25. Tonicity Agents:-
For comfort during administration, many dosage forms must be "isotonic" or having the same salt concentration as the normal cells of the body and the blood. Tonicity agents are added to injectable, ocular or nasal preparations to reduce local irritation by preventing osmotic shock at the site of injection/application.
Example:-
o Dextrose, Anhydrous, Granular, USP, EP, BP, JP
o Dextrose, Hydrous, Powder, USP
o Glycerin, Natural, USP, EP, BP, JP
o Glycerin, Synthetic, USP, EP, BP, JP
o Mannitol, Powder, USP
o Potassium Chloride, Crystal, USP
26. Vehicles:-
Drug delivery technologies are patent-protected formulation technologies that modify drug release profile, absorption, distribution and elimination for the benefit of improving product efficacy and safety, as well as patient convenience and compliance. Most common methods of delivery include the oral, topical (skin), transmucosal (nasal, vaginal, ocular and rectal) and inhalation routes.
Example:-
o Almond Oil, Sweet, NF
o Corn Oil, NF
o Cottonseed Oil, NF
o Dextrose, Anhydrous, Granular, USP, EP, BP, JP
o Dextrose, Hydrous, Powder, USP
o Ethyl Oleate, NF
o Isopropyl Palmitate, NF
27. Wetting Agents:-
In pharmaceutical liquid dosage forms, surfactants often function as wetting agents, where they reduce interfacial tension. In lotions and sprays wetting agents help the preparation spread on the skin surface. In oral dosage forms they aid in creating a homogeneous dispersion of solid particles in a liquid vehicle. Surfactants are usually organic compounds that are amphiphilic, meaning they contain both hydrophobic groups (their tails) and hydrophilic groups (their heads). Therefore, a surfactant molecule contains both a water insoluble (or oil soluble) component and a water soluble component. Surfactant molecules will diffuse in water and adsorb at interfaces between air and water or at the interface between oil and water, in the case where water is mixed with oil. The insoluble hydrophobic group may extend out of the bulk water phase, into the air or into the oil phase, while the water soluble head group remains in the water phase. This alignment of surfactant molecules at the surface modifies the surface properties of water at the water/air or water/oil interface.
Example:-
o Benzalkonium Chloride, NF
o Benzethonium Chloride, USP
o Cetylpyridinium Chloride, Monohydrate, USP
o Docusate Sodium, USP
o Poloxamer 407, NF
o Poloxamer 188, NF
o Poloxamer 338, NF
o Polyoxyl 40 Stearate, NF
o Polysorbate 20, NF
o Polysorbate 40, NF
6. Reference:-
Excipient Development for Pharmaceutical, Biotechnology,and Drug Delivery Systems by Ashok Katdare,Informa Healthcare USA, Inc.
www.pharmagupshup.in
Excipient Master File Guide by Christopher C.DeMerlis,Pharmaceutical Technology, June 2002
Excipient Functionality by R. Christian Moreton, Pharmaceutical Technology, May 2004
USP 2007
IP 2007
http://en.wikipedia.org
https://www.spectrumchemical.com
http://www.britannica.com
Excipient interaction by Patrick, Pharmaceutical Technology, May 2004
An excipient is generally a pharmacologically inactive substance used as a carrier for the active ingredients of a medication. In many cases, an "active" substance (such as acetylsalicylic acid) may not be easily administered and absorbed by the human body; in such cases the substance in question may be dissolved into or mixed with an excipient. Excipients are also sometimes used to bulk up formulations that contain very potent active ingredients, to allow for convenient and accurate dosage. In addition to their use in the single-dosage quantity, excipients can be used in the manufacturing process to aid in the handling of the active substance concerned. Depending on the route of administration, and form of medication, different excipients may be used. For oral administration tablets and capsules are used. Suppositories are used for rectal administration.
Often, once an active ingredient has been purified, it cannot stay in purified form for long. In many cases it will denature, fall out of solution, or stick to the sides of the container. To stabilize the active ingredient, excipients are added, ensuring that the active ingredient stays "active", and, just as importantly, stable for a sufficiently long period of time that the shelf-life of the product makes it competitive with other products. Thus, the formulation of excipients in many cases is considered a trade secret.
Pharmaceutical codes require that all ingredients in drugs, as well as their chemical decomposition products, be identified and guaranteed to be safe. For this reason, excipients are only used when absolutely necessary and in the smallest amounts possible.
1.1 Objective:
Excipients are now known to have defined functional roles in pharmaceutical dosage forms
(i) Modulating solubility and bioavailability of the active ingredient(s)
(ii) Enhancing stability of the active ingredient(s) in finished dosage forms
(iii) Helping active ingredients maintain a preferred polymorphic form or conformation
(iv) Maintaining pH and osmolarity of liquid formulations
(v) Acting as antioxidants, emulsifying agents, aerosol propellants, tablet binders, and tablet disintegrants
(vi) Preventing aggregation or dissociation;
(vii) Modulating the immunogenic response of active ingredients (e.g., adjuvants) and many others.
United States Pharmacopeia 28–National Formulary 23 lists 40 functional categories of excipients for pharmaceuticals, and many more are expected as new—and usually increasingly complex—drug-delivery systems emerge and evolve. Approximately 800 excipients are currently used in the marketed pharmaceutical products in the United States. This number is also expected to grow with new therapeutic categories, such as gene therapy and cell therapy, and new drug delivery technologies.
Excipients can themselves affect safety and efficacy outcomes. Excipients, or their impurities, can be associated with adverse events, either by direct action or by formation of undesirable adducts. By modifying absorption and, for parenteral products, distribution, excipients can change exposure patterns and thus influence both safety and efficacy outcomes. Excipients are well known to affect the safety and efficacy profiles of locally acting products. As adjuvants, excipients required for protein and conjugate vaccines play a crucial role in the immunogenic properties of vaccines. ‘‘New excipients’’: These may require careful and, not uncommonly, extensive safety studies, with corresponding careful attention to characterization and specification setting. At present, new excipients in the United States do not undergo separate approval but attain market access frequently via a regulatory process in association with the new drug application process for a dosage form.
According to IP 2007
Any substance added in preparing an official preparation shall be innocuous, shall have no adverse influence in the therapeutic efficacy of the active ingredients and shall not interfere with the tests and assays of the Pharmacopoeia. Care should be taken to ensure that such substances are free from harmful organisms.
2.0 Regulation of Pharmaceutical Excipients:-
The U.S. Food and Drug Administration (FDA) does not have a formal regulatory definition of ‘‘excipient’’; however, recent guidance on nonclinical safety studies for excipients provides some indication of FDA acceptance of excipients as more than fillers. The background section of that guidance states:
In this guidance, the phrase new excipients means any inactive ingredients that are intentionally added to therapeutic and diagnostic products, but that: (i) we believe are not intended to exert therapeutic effects at the intended dosage, although they may act to ‘‘improve product delivery’’ (e.g., enhance absorption or control release of the drug substance); and (ii) are not fully qualified by existing safety data with respect to the currently proposed level of exposure, duration of exposure, or route of administration. Examples of excipients include fillers, extenders, diluents, wetting agents, solvents, emulsifiers, preservatives, flavors, absorption enhancers, sustained-release matrices, and coloring agents (emphasis added).
The Agency set out six criteria for an excipient in an OTC product as follows:
1. The ingredient is listed in an official compendium [e.g., USP/National Formulary (NF)] as a pharmaceutical aid or performed certain physical or technical functions in the final formulations (as will be set forth below).
2. The inactive ingredient is used at a level no higher than reasonably required to achieve its physical or technical function. For example, an antimicrobial excipient ingredient could only be used at a level consistent with preservation of the finished product (not at therapeutic levels), and a sunscreen ingredient could only be used at levels that protected the product from breaking down if the top of the jar was left open, not for protecting the user.
3. It is safe when at levels used as inactive ingredient.
4. If it is a color, it must meet appropriate color additive regulations.
5. It does not interfere with the effectiveness of the product. For example, fluoride toothpastes have to be formulated carefully, as the various fluorides react with certain excipients, rendering the product ineffective.
6. The inactive ingredient does not interfere with suitable tests or assays used to assure the identity, quality, strength, or purity of the finished product.
The FDA then set forth a list of 23 physical or technical functions these excipients perform as follows:
1. Air displacement agents: substances that displace air.
2. Color additives: as defined in Section 201(t) of the Act.
3. Denaturing agents: substances added to alcohol to render it unfit for use as an intoxicating beverage.
4. Dispersing agents: substances that promote even distribution throughout a liquid, gaseous, or solid medium with the formulation of a two-phase system.
5. Emollients: bland, fatty, or oleaginous substances that may be applied locally, particularly to the skin, and also to mucous membranes or abraded tissue.
6. Emulsifiers and emulsifying salts: substances that modify surface tension in the component phase of an emulsion to establish a uniform dispersion or emulsion.
7. Flavors and flavoring adjuncts: substances added to impart or help impart a taste or aroma to a product.
8. Fragrances: substances, extracts, or preparations for fragrance diffusing or imparting an agreeable or attractive odor.
9. Humectants: hygroscopic substances incorporated in a product to promote retention of moisture, including moisture retention agents and antidusting agents.
10. Identifiers: substances incorporated in a product to aid manufacturers to distinguish their products from similar or counterfeit products.
11. Levigating agents: substances that aid in reducing another substance to an extremely fine state of subdivision after that other substance has been made into a paste with some suitable liquid in which it is insoluble; also, nonsolid vehicles used to disperse a solid substance to a paste.
12. Ointment bases: vehicles to permit topical application of active medicinal substances.
13. PH control agents: substances added to change or maintain active acidity or basicity, including buffers, acids, alkalies, and neutralizing agents.
14. Preservatives: substances that are added to preparations to prevent or retard deterioration or degradation in a product; such substances include antifungal agents, antioxidants, antimicrobial agents, mold and rope inhibitors, and agents having the effects listed by the National Academy of Sciences—National Research Council under ‘‘preservatives.’’ For the purpose of this section, ‘‘antioxidant’’ is defined as a substance that inhibits oxidation and is used to prevent rancidity of oils or fats or the deterioration of other materials through oxidative processes, including color changes.
15. Propellants, aerating agents, and gases: gases used to supply force to expel a product or used to reduce the amount of oxygen with the product in packaging.
16. Solvents and vehicles: substances used to dissolve or extract another substance or used as carriers of other substances.
17. Stiffening agents: substances that increase the viscosity of certain pharmaceutical preparations, especially ointments.
18. Suppository bases: pharmaceutical bases those are solid at room temperature but melt at body temperature.
19. Surface-active agents: substances used to modify the surface properties of liquids for a variety of effects. The definition includes solubilizing agents, dispersants, detergents, wetting agents, dehydration enhancers, whipping agents, foaming agents, and defoaming agents.
20. Suspending agents: substances required to overcome agglomeration of the dispersed particles and increase the viscosity of the medium so that the particles settle slowly.
21. Tablet and capsule diluents: inert substances incorporated to increase the bulk, to make the tablet or capsule of practical size.
The FDA looks to several sources to identify these previously reviewed excipients, including food additive or food GRAS status, favorable review by JECFA, inclusion in the USP/NF, or prior review in other new drug applications. These previously used/acceptable excipients are identified in the FDA’s Inactive Ingredient Guide. Inclusion of an ingredient in this guide provides the FDA a reasonable assurance that an ingredient, used within the scope of the usage provided in the guide, will be acceptable. Therefore, regulation of well-known excipients in both OTC and prescription drugs are subject to a reasonably certain set of procedures. However, the lack of an independent review for excipients creates significant issues for companies that wish to use new or novel excipients in their drug products. Lack of any independent review means that there is no formal mechanism for providing indicia of acceptability by regulatory agencies, and this creates uncertainties that reduce incentives to develop and use novel ingredients. Despite this lack of formal review, there has been some movement toward mechanisms to address this problem, but official independent status and review of excipients is not likely or necessarily in the best interests of industry or the regulatory agencies.
3.0 EXCIPIENT INTERACTIONS:-
Excipient interactions are a large part of why medicines work (and sometimes why they do not work in development). They can be either beneficial or detrimental, and can be classified simply as
physical,
chemical, and
Physiological/biopharmaceutical.
Physical interactions do not involve chemical change. The components retain their molecular structure. Chemical interactions, on the other hand, involve chemical reactions; i.e., a different molecule (or molecules) is (are) created. Physiological interactions are the interactions between the excipient(s) and the body fluids.
The significance of excipient interactions can extend well beyond the development of the particular medicinal product. Excipient interactions can have implications for
drug stability,
product manufacture,
drug release (dissolution; both in vitro and in vivo),
therapeutic activity, and
Side effect profile.
3.1 Physical Interactions:-
Physical interactions involving excipients are quite common. However, they are also the most difficult to detect because there is often no convenient chemical ‘‘handle,’’as is usually the case with a chemical interaction. Physical interactions are frequently used in pharmaceutical science, for example, to aid processing and to aid or modify drug dissolution (such as oral modified release) or distribution in the body (such as with the use of a parenteral modified release product). Some of these interactions are deliberately invoked to produce a certain effect. Others are unintended, and it is these interactions that usually cause the problems. When considering physical interactions, particularly the ability to predict them in terms of product stability, differential scanning calorimetry (DSC)
Example of an excipient–excipient interaction that can be used to our advantage is the one between xanthan gum and locust bean gum (carob gum or ceratonia) in the presence of water. This interaction forms the basis of the identification test for Xanthan Gum NF. The interaction creates a much more viscous gel system than can be created using either component alone. This has been used in the formulation of controlled release oral solid dosage forms.
3.2 Chemical Interactions:-
Chemical interactions are almost always detrimental to the product because they usually indicate an incompatibility that gives rise to chemical compounds that would be classified as degradation products under ICH Q3B, thus leading to requirements for quantitation, identification, and ultimately qualification (some form of safety assessment) depending on the level found.
Example: Certain APIs are susceptible to oxidation, e.g., atorvastatin and cytidine nucleoside analogues. Fumed metal oxides (e.g., fumed silica, fumed titania, and fumed zirconia) can promote such oxidation reactions. These reactions are more complex in some ways, and less easy to predict.
3.3 PHYSIOLOGICAL/BIOPHARMACEUTICAL INTERACTIONS:-
All excipients interact in a physiological sense when they are administered as part of the medicine. For example, we can get dilution of the vehicle leading to changes in viscosity or precipitation of the drug, disintegration of a tablet or capsule, activation of a controlled release mechanism, etc. This may be stating the obvious to many, but in many instances this interaction with physiological fluids is not actively considered; although it may be understood or assumed to be occurring. However these physiological interactions are very important for the correct functioning of the product, and it is thus important to understand when other interactions occur and what the physiological impact will be. For example, we consider the physical properties of magnesium stearate as a tablet or capsule lubricant, but, as was discussed in ‘‘Physical Interaction’’ section, it is well documented in the literature that when magnesium stearate is used incorrectly these same physical properties can lead to problems that can impact dissolution, and thus could possibly affect bioavailability.
Example: classic biopharmaceutical incompatibility is the interaction between tetracycline antibiotics and calcium and magnesium ions (30). A complex is formed that is not absorbed from the GIT. This is a well-known interaction, and tetracycline antibiotics usually carry a warning against taking them with certain types of food. But magnesium and calcium salts are quite common excipients, in terms of both the range of formulations containing them and the level of inclusion in those formulations.
5.0 Various e Excipient:-
Different Formulation have different excipient .tablet, capsule etc. have different formulation. Various excipients are as follows:
1. Acidifying Agent:
They are used in liquid preparations to provide acidic medium for product stability. PH modifiers such as acidifying agents are important in pharmaceutical and cosmetic formulations where the active pharmaceutical ingredient requires an acidic environment for stability or therapeutic effectiveness.
Example:
o Anhydrous Citric Acid, Powder, USP
o Citric Acid Monohydrate, Crystalline Powder, USP
o Citric Acid Monohydrate, Granular, USP
o Diluted Hydrochloric Acid, 10 Percent (w/v), NF
o Fumaric Acid, NF
o Hydrochloric Acid, 37 Percent, NF
o Malic Acid, NF
o Phosphoric Acid, NF
o Propionic Acid, NF
o Pyronin Y
o Sulfuric Acid, NF
o Tartaric Acid, Granular, NF
2. Denatured alcohol
It is used as a solvent and as fuel for spirit burners and camping stoves. Because of the diversity of industrial uses for denatured alcohol, hundreds of additives and denaturing methods have been used. The main additive has traditionally been 10% methanol, giving rise to the term "methylated spirit. ther typical additives include isopropyl alcohol, acetone, methyl ethyl ketone, methyl isobutyl ketone, and denatonium. Denatured alcohol provides a solution to permit legitimate use and manufacture of ethanol, whereby cheap ethanol can be made available for non-consumption use without the risk of its being converted for consumption. The process creates an ethanol-containing solution that is not suitable for drinking, but is otherwise similar to ethanol for most purposes. As a result, there is no duty on denatured alcohol in most countries, making it considerably cheaper than pure ethanol. As a consequence, its composition is tightly defined by government regulations that vary between countries.
Formulation:
Completely denatured alcohol must be made in accordance with the following formulation: with every 90 parts by volume of alcohol mix 9.5 parts by volume of wood naphtha or a substitute for wood naphtha [note that methanol is not permissible in place of wood naphtha] and 0.5 parts by volume of crude pyridine, and to the resulting mixture add mineral naphtha (petroleum oil) in the proportion of 3.75 litres to every 1000 litres of the mixture and synthetic organic dyestuff (methyl violet) in the proportion of 1.5 grams to every 1000 litres of the mixture.
Denatured alcohol has a variety of common uses:
* As a fuel for marine and ultra-light camping (backpacking) stoves. It is inexpensive, may be extinguished with water, and can be transported without special containers. However, safety concerns do arise from the near-colourless flame with which alcohol burns. A jellied and dyed form is used in the Sterno brand fuel "Canned Heat", and is meant to be ignited and used in the container.
* To pre-heat the vaporizing tubes on wickless paraffin stove such as a Primus stove
* As a sanding aid, as the alcohol helps to more easily remove excess dust because it does not open the wood grain the way that water does.
* As a mealybug exterminator.
* As a cleaning aid in removing ink stains from upholstery or clothes.
* As a cleaner in daily housekeeping
* To disinfect skin prior to an injection or minor surgery, such as draining a blister (also see rubbing alcohol).
* As an antiseptic for minor wounds.
* As a solvent in shellac and shellac-based products.
* As an excipient in a number of pharmaceutical products for oral and topical use.
* As a less expensive alternative to pure ethanol in preserving biological specimens.
* As a less toxic alternative to methanol in the production of biodiesel fuel. Biodiesel produced using ethanol is properly called fatty acid ethyl ester, whereas biodiesel from methanol is properly referred to as fatty acid methyl ester.[6]
* As a germicide in the removal of fungus from skin and coldsore treatment.
* For maintenance of wicks in kerosene heaters and lamps to remove water contaminants and restore the capillary action of the wick. As a wick cleaner and a kerosene additive, adding approx. 1 teaspoon denatured alcohol per gallon of kerosene.
* As a fuel for older toy steam engines which used a wick-type or vapourising burner.
* For window washing.
3. Alkalizing Agents
pH modifiers such as alkalizing agents are important in pharmaceutical and cosmetic formulations where the active pharmaceutical ingredient requires an alkaline environment for stability or therapeutic effectiveness.
Example:
o Ammonium Carbonate, Powder, NF
o Diethanolamine, NF
o Potassium Hydroxide, Pellets, NF
o Sodium Bicarbonate, Powder, USP, EP, BP, JP
o Sodium Borate, Decahydrate, NF
o Sodium Carbonate, Hydrous, NF
o Sodium Hydroxide, Pellets, NF
o Strong Ammonia Solution, NF
o Zinc Carbonate, USP
4.Antimicrobial or Preservatives:-
A preservative is a naturally occurring or synthetically produced substance that is added to products such as foods, pharmaceuticals, paints, biological samples, wood, etc. to prevent decomposition by microbial growth or by undesirable chemical changes. The ideal preservative for food, pharmaceutical and nutraceutical products is effective at low concentrations against a wide spectrum of microbes, soluble in the formulation, non-toxic and non-sensitizing, stable over a wide range of pH and temperature and inexpensive.
Example:
o Benzalkonium Chloride, NF
o Benzalkonium Chloride Solution, 50 Percent, NF
o Benzethonium Chloride, USP
o Benzoic Acid, Crystal, USP, EP, BP, JP
o Benzoic Acid, Flake, USP, EP, JP
o Benzyl Alcohol, NF
o Butylparaben, NF
o Cetylpyridinium Chloride, Monohydrate, USP
o Chlorobutanol, Anhydrous, NF
o Chlorobutanol, Hydrous, NF
o Ethylparaben, NF
o Methylparaben, NF
o Methylparaben Sodium, NF
5. Antioxidant:-
An antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When the chain reaction occurs in a cell, it can cause damage or death to the cell. Antioxidants terminate these chain reactions by removing free radical intermediates, and inhibit other oxidation reactions. They do this by being oxidized themselves, so antioxidants are often reducing agents such as thiols, ascorbic acid, or polyphenols. Antioxidants are widely used as ingredients in dietary supplements and have been investigated for the prevention of diseases such as cancer, coronary heart disease and even altitude sickness. Although initial studies suggested that antioxidant supplements might promote health, later large clinical trials did not detect any benefit and suggested instead that excess supplementation is harmful. In addition to these uses of natural antioxidants in medicine, these compounds have many industrial uses, such as preservatives in food and cosmetics and preventing the degradation of rubber and gasoline.
Example:
o Ascorbic Acid, USP
o Ascorbyl Palmitate, NF
o Butylated Hydroxyanisole, Flakes, NF
o Butylated Hydroxytoluene, Granular, NF
o Potassium Metabisulfite, Crystal, NF
o Propyl Gallate, NF
o Sodium Metabisulfite, Granular, NF, EP, BP, JP
o Sodium Thiosulfate, Pentahydrate, Crystal, USP, EP, BP, JP
o Vitamin E, 1 mg = 1.1 IU, USP
6. Ointment Bases:-
An ointment is a homogeneous, viscous, semi-solid preparation, most commonly a greasy, thick oil (oil 80% - water 20%) with a high viscosity, that is intended for external application to the skin or mucous membranes. They are used as emollients or for the application of active ingredients to the skin for protective, therapeutic, or prophylactic purposes and where a degree of occlusion is desired.Ointments are used topically on a variety of body surfaces. These include the skin and the mucous membranes of the eye (an eye ointment), vagina, anus, and nose. An ointment may or may not be medicated.
The vehicle of an ointment is known as the ointment base. The choice of a base depends upon the clinical indication for the ointment. The different types of ointment bases are:
o Hydrocarbon bases, e.g. hard paraffin, soft paraffin, microcrystalline wax and ceresine
o Absorption bases, e.g. wool fat, beeswax
o Water soluble bases, e.g. macrogols 200, 300, 400
o Emulsifying bases, e.g. emulsifying wax, cetrimide
o Vegetable oils, e.g. olive oil, coconut oil, sesame oil, almond oil and peanut oil.
The medicaments are dispersed in the base, and later they get divided after the drug penetration into the living cells of skin.Ointments are formulated using hydrophobic, hydrophilic, or water-emulsifying bases to provide preparations that are immiscible, miscible, or emulsifiable with skin secretions. They can also be derived from hydrocarbon (fatty), absorption, water-removable, or water-soluble bases.
Example:
Lanolin, USP
Petrolatum, Yellow, USP
Squalane, NF
White Petrolatum, White, USP
7. Suppository Bases:-
Suppository bases are used in the manufacture of suppositories (for rectal administration) and pessaries (for vaginal administration). They can be hydrophobic or hydrophilic. Suppositories should melt at just below body temperature (37° C), which allows for erosion of the dosage form and release of the API. Hard fat suppository bases melt at approximately body temperature. Hydrophilic suppository bases also melt at body temperature, and typically also dissolve or disperse in aqueous media. This allows release to take place via a combination of erosion and dissolution.
Example:
o Cocoa Butter, NF
o Polyethylene Glycol 1000, NF
o Polyethylene Glycol 8000, NF
o Polyethylene Glycol 4500, NF
o Polyethylene Glycol 300, NF
o Polyethylene Glycol 400, NF
o olyethylene Glycol 600, NF
8. Binders:-
When pharmaceutical ingredients cannot be directly compressed to form a tablet, wet granulation must be used. Binders facilitate agglomeration of powder into granules in this process. They are typically dissolved or dispersed in the granulation fluid (usually water or alcohol), or blended dry with the other formulation components before the granulation fluid is added. After initial pelletting, the liquid is evaporated and the binders serve to maintain the resulting dry granules in the appropriate size. They might also affect granule properties such as flow, handling, strength, solubility, compaction, or drug release.
Example:-
o Acacia, Milled Powder, NF
o Acacia, Spray-Dried Powder, NF
o Alginic Acid, NF
o Corn Starch, Powder, NF
o Ethylcellulose, NF
o Gelatin, Powder, NF
o Guar Gum, NF Hypromellose, Substitution Type 2208, 100,000 mPa.s, USP
o Hypromellose, Substitution Type 2208, 100,000 mPa.s, USP
9. Buffering Agents:-
A buffering agent is a weak acid or base used to maintain the acidity (pH) of a solution at a chosen value. The function of a buffering agent is to prevent a rapid change in pH when acids or bases are added to the solution. Buffering agents have variable properties—some are more soluble than others; some are acidic while others are basic. Buffer concentrations are generally between 0.01 and 0.1 M. Formulators select buffers depending on their suitability for use in oral liquids, the stability of the formulation in the presence of the buffer, and compatibility of the buffer with the product container. A buffering agent can be either a weak acid or weak base. Buffering agents are usually added to water to form a buffer solution, which maintains a stable pH in spite of other acids and bases being combined with it. For example, buffered aspirin has a buffering agent, such as MgO, that will maintain the pH of the aspirin as it passes through the acidic stomach of the patient. Another use of a buffering agent is in an antacid tablet, whose primary purpose is to lower the acidity of the stomach.
Example:
o Ammonium Carbonate, Powder, NF
o Ammonium Phosphate, Granular, NF
o Anhydrous Citric Acid, Powder, USP
o Boric Acid, Crystal, NF
o Boric Acid, Granular, NF, EP, BP, JP
o Boric Acid, Powder, NF
o Citric Acid Monohydrate, Crystalline Powder, USP
o Citric Acid Monohydrate, Granular, USP
o Dibasic Potassium Phosphate, Anhydrous, USP, EP, BP
o Lactic Acid, Racemic, USP
o MES, Hemisodium Salt, Biological Buffer
o MOPS Hemisodium Salt, Biological Buffer
10. Chelating Agents:-
Chelation therapy is the use of chelating agents to detoxify poisonous metal agents such as mercury, arsenic, and lead by converting them to a chemically inert form that can be excreted without further interaction with the body.
Example:
o Edetate Calcium Disodium, Hydrate, USP
o Edetate Disodium, Dihydrate, USP
o Edetic Acid, NF
11. Coating Agents
Coating agents are used to form a protective layer over inflamed mucous membranes and skin and to promote more rapid resolution of inflammatory processes. They include starch, aluminum hydroxide, white clay, magnesium trisilicate, and flaxseed. Coating agents are tasteless and disguise the flavor of substances with which they are mixed. Their presence in the intestinal tract diminishes the effect of irritants and delays the absorption of water, food, and medicinal substances. Coating agents also prolong the local effects of medicinal substances on the intestinal tract.
Coating agents are used to treat inflammations of the mucosa of the oral cavity, throat, and gastrointestinal tract and to treat poisoning by irritants and caustic substances. They are also used in mixtures to avoid the irritant side effects of certain medicines and to prolong the duration of local action of various substances.
The ingredients of coating agents include finely ground powders that are highly adsorptive. This property enables these substances to be used in cases of poisoning to limit the absorption of toxins, for example, in poisoning by many salts of alkaloids and heavy metals. Coating agents in the form of powders are also used in the treatment of skin diseases.
Example:
o Ethylcellulose, NF
o Gelatin, Powder, NF
o Hydroxypropyl Cellulose, 4,000-6,500 cps, NF
o Hydroxypropyl Cellulose, 150-400 cps, NF
o Hydroxypropyl Cellulose, 75-100 cps, NF
o Hypromellose, Substitution Type 2208, 100,000 mPa.s, USP
12. Color Agents
Coloring agents produce a distinctive appearance that may serve to differentiate a particular formulation from others that have a similar physical appearance. These substances are subdivided into dyes, inorganic pigments and natural colorants. Coloring agents are subject to federal regulations, and consequently the current regulatory status of a given substance must be determined before its use.Used to impart color to liquid solid tablet and capsule preparations.
Example:
o Caramel, Color, NF
o D and C Green No. 5
o D and C Green No. 6
o D and C Green No. 8
o D and C Orange No. 4
o D and C Red No. 17
o D and C Red No. 22
o D and C Red No. 28
o D and C Red No. 4
o D and C Red No. 6
o D and C Red No. 33
o D and C Violet No. 2
o D and C Yellow No. 11
o D and C Yellow No. 8
o D and C Yellow No. 10
o FD and C Black Shade
o FD and C Blue No. 1
o FD and C Blue No. 2
o FD and C Carmine
o FD and C Emerald Green
o FD and C Green No. 3
o FD and C Red No. 3
o FD and C Red No. 40
o FD and C Yellow No. 5
o FD and C Yellow No. 6
13. Diluents:-
Diluents, sometimes called fillers, increase dosage form, volume, or weight of a pharmaceutical product. Because most dosages require only very small quantities of Active Pharmaceutical Ingredients (APIs), diluents often comprise a significant proportion of the dosage form. This means their physical and chemical properties are key variables in the manufacturing and performance of the product, and should be clearly understood and tightly controlled.
Diluents are also very important in the pharmaceutical industry. They are inactive ingredients that are added to tablets and capsules in addition to the active drug. For example, a Tylenol 325 mg tablet does not weigh 325 mg. This is the weight of the active acetaminophen, while the tablet weighs more due to other additives known as diluents. These additives may be used as binders, disintegrants (help the tablet break apart in the digestive system), or flavor enhancers. Some very common diluents in tablets include starch, cellulose derivatives, and magnesium stearate (a lubricant).
Example:-
o Anhydrous Dibasic Calcium Phosphate, Powder, USP
o Anhydrous Lactose, NF
o Calcium Carbonate, Heavy Powder, USP
o Calcium Carbonate, Light Powder, USP
o Calcium Sulfate, Dihydrate, NF
o Corn Starch, Powder, NF
o Dextrates, Hydrated, NF
o Fructose, Granular, USP
o Kaolin, Powder, USP
o Lactose, Monohydrate, Powder, NF
o Lactose, Monohydrate, Spray-Dried Powder, NF
o Maltitol Solution, NF
14. Disintegrants:-
Disintegrants expand and dissolve when wet causing the tablet to break apart in the digestive tract, releasing the active ingredients for absorption. Disintegrants are agents added to tablet (and some encapsulated) formulations to promote the breakup of the tablet (and capsule “slugs”) into smaller fragments in an aqueous environment, thereby increasing the available surface area and promoting a more rapid release of the drug substance. They ensure that when the tablet is in contact with water, it rapidly breaks down into smaller fragments, facilitating dissolution.
Example:-
o Alginic Acid, NF
o Corn Starch, Powder, NF
o Croscarmellose Sodium, NF
o Microcrystalline Cellulose, NF
o Sodium Starch Glycolate, pH 5.5-7.5, Type A, NF
15. Emulsifying Agents:-
An emulsion is a mixture of two or more immiscible (unblendable) liquids. An emulsifying is a substance which stabilizes an emulsion. In pharmaceutics, hairstyling, personal hygiene and cosmetics, emulsions are frequently used and are usually oil and water emulsions.
'USED TO PROMOTE AND MAINTAIN DISPERSION OF FINELY SUBDIVIDED PARTICLES IN A LIQUID VECHICLE IN WHICH IT IS IMMISCIBLE'
Example:
o Acacia, Milled Powder, NF
o Acacia, Spray-Dried Powder, NF
o Carbomer 940, NF
o Carbomer 941, NF
o Carbomer 1342, NF
o Carbomer 934, Resin, Powder, NF
o Carbomer 934P, Resin, NF
o Cholesterol, NF
o Diethanolamine, NF
o Emulsifying Wax, NF
16. Flavor Agents:-
Flavoring agents alter the sensory impression of a substance mainly by the chemical senses of taste and smell. Of the chemical senses, smell is the main determinant of a food item's flavor.
Example:-
o Almond Oil, Sweet, NF
o Benzaldehyde, NF
o DL-Menthol, Crystal, USP
o Ethyl Acetate, NF
o Ethyl Vanillin, NF
o L-Menthol, Crystal, USP
o Methyl Salicylate, NF
17. Glidants:-
A glidant is a substance that is added to a powder to improve its flowability. A glidant will only work at a certain range of concentrations. Above a certain concentration, the glidant will in fact function to inhibit flowability (Which means that there's a critical concentration to be used if increasing powder's flowability is intended with respect to the glidant and the powder properties). In tablet manufacture, glidants are usually added just prior to compression.
Mechanism Of Action:A Glidant's effect is due to a counter-action to factors resulting in poor flowability of powders. For instance, correcting surface irregularity, reducing interparticular friction & decreasing surface charge. The result is a decrease in the angle of repose which is an indication of an enhanced powder's flowability.
Example:
o Calcium Silicate, NF
o Colloidal Silicon Dioxide, NF, EP
o Talc, Powder, USP
18. Humectants:-
Humectants are while used in pharmaceutical packaging, they most often found within the pharmaceutical formulation itself, where humectants control the moisture content of the pharmaceutical dosage form. Humectants are also used in topical dosage forms to increase the solubility of the active ingredient, to elevate its skin penetration and increase its activity time. Humectants also elevate the hydration of the skin to minimize the dehydrating effect of some active ingredients like corticoids. Examples of humectants include propylene glycol (E1520), glyceryl triacetate (E1518), vinyl alcohol and neoagarobiose. Others can be sugar polyols such as glycerol, sorbitol (E420), xylitol and maltitol (E965), polymeric polyols like polydextrose (E1200), or natural extracts like quillaia (E999), lactic acid, or urea.
19. Lubricants:-
Lubricant excipients decrease friction between the pharmaceutical or nutraceutical preparation’s particles and the tableting equipment contact surfaces.A lubricant is a substance introduced to reduce friction between moving surfaces. It may also have the function of transporting foreign particles. The property of reducing friction is known as lubricity.
A good lubricant possesses the following characteristics:
o High boiling point.
o Low freezing point.
o High viscosity index.
o Thermal stability.
o Corrosion prevention.
o High resistance to oxidation.
Example:
o Calcium Silicate, NF
o Calcium Stearate, NF
o Colloidal Silicon Dioxide, NF, EP
o Magnesium Stearate, NF, BP, JP
o Polyethylene Glycol 8000, NF
o Polyethylene Glycol 4500, NF
o Polyoxyl 40 Stearate, NF
o Polysorbate 20, NF
o Polysorbate 40, NF
20. Plasticizers:-
Plasticizers (UK = plasticisers) or dispersants are additives that increase the plasticity or fluidity of a material. The dominant applications are for plastics, especially polyvinyl chloride (PVC).Selection of the appropriate excipient plasticizer will provide the desired flexibility and permeability on the finished film coating. Properly plasticized films provide both physical and environmental protection to the coated product in transport and storage. Some plasticizer excipients are effective in retarding drug release in acid media, making them an excellent choice for enteric protection.
Example:
o Castor Oil, USP
o Diethyl Phthalate, NF
o Glycerin, Natural, USP, EP, BP, JP
o Glycerin, Synthetic, USP, EP, BP, JP
o Polyethylene Glycol 1000, NF
o Polyethylene Glycol 8000, NF
o Polyethylene Glycol 4500, NF
o Polyethylene Glycol 300, NF
o Polyethylene Glycol 400, NF
o Polyethylene Glycol 600, NF
o Polyethylene Glycol 1500, NF
o Polyethylene Glycol 1450, NF
o Polyethylene Glycol 3350, NF
o Propylene Glycol, USP
o Triacetin, USP
o Triethyl Citrate, FCC
21. Solvents:-
Solvents are used in hundreds of pharmaceutical products. Ointments and other topical products, such as antibacterial creams and corticosteroids, often use solvents in the beginning of the process to manufacture the active ingredients. As the drug is being transformed into its final form, whether cream, lotion or liquid, solvents are used as a medium for blending materials. Solvents also are used to help the final product achieve the proper consistency.
Example:-
o Alcohol, 190 Proof, USP
o Benzyl Benzoate, USP
o Butyl Alcohol, NF
o Corn Oil, NF
o Cottonseed Oil, NF
o Dehydrated Alcohol, 200 Proof, Undenatured, USP
o Ethyl Alcohol, MultiPharm, 200 Proof, EP, JP, USP
o Glycerin, Natural, USP, EP, BP, JP
o Glycerin, Synthetic, USP, EP, BP, JP
o Isopropyl Alcohol, 70 Percent, USP
o Isopropyl Alcohol, 99 Percent, USP, EP, BP, JP
o Light Mineral Oil, NF
22. Stiffening agents:-
They are used primarily in topical preparations for increasing the preparation viscosity. Often stiffening agents find application as sustained-release carriers and to minimize sweating and bleeding of oil-wax blends.
Example:-
o Cetyl Alcohol, NF
o Cetyl Esters Wax, Synthetic, NF
o Emulsifying Wax, NF
o Paraffin, NF
o Stearyl Alcohol, NF
o White Wax, Cake, NF
23. Suspending / Thickening Agents:-
In a pharmaceutical or cosmetic suspension, a suspending agent helps the active ingredient stay in the body of the suspension thereby preventing caking at the bottom. One of the properties of a well-formulated suspension is that it can be easily re-suspended by the use of moderate agitation.
Example:-
o Acacia, Milled Powder, NF
o Acacia, Spray-Dried Powder, NF
o Agar, Flake, NF
o Agar, Granular, NF
o Agar, Powder, NF
o Alginic Acid, NF
o Aluminum Monostearate, NF
o Bentonite, Powder, NF
o Carbomer 940, NF
o Carbomer 941, NF
o Carbomer 1342, NF
24. Sweetening Agents:-
Sweetening agents are substances that sweeten food, beverages, medications, etc., such as sugar, saccharine or other low-calorie synthetic products Sweeteners are added to make the ingredients more palatable, especially in chewable tablets such as antacid or liquids like cough syrup. Sugar can be used to mask unpleasant tastes or smells.
Example:-
o Aspartame, Powder, NF
o Dextrates, Hydrated, NF
o Dextrose, Anhydrous, Granular, USP, EP, BP, JP
o Dextrose, Hydrous, Powder, USP
o Fructose, Granular, USP
o Maltitol Solution, NF
o Mannitol, Powder, USP
o Saccharin Calcium, Crystal, USP
o Saccharin, Powder, NF
o Saccharin Sodium, Dihydrate, Granular, USP
o Sorbitol, Powder, NF
o Sorbitol Solution, 70 Percent, US
25. Tonicity Agents:-
For comfort during administration, many dosage forms must be "isotonic" or having the same salt concentration as the normal cells of the body and the blood. Tonicity agents are added to injectable, ocular or nasal preparations to reduce local irritation by preventing osmotic shock at the site of injection/application.
Example:-
o Dextrose, Anhydrous, Granular, USP, EP, BP, JP
o Dextrose, Hydrous, Powder, USP
o Glycerin, Natural, USP, EP, BP, JP
o Glycerin, Synthetic, USP, EP, BP, JP
o Mannitol, Powder, USP
o Potassium Chloride, Crystal, USP
26. Vehicles:-
Drug delivery technologies are patent-protected formulation technologies that modify drug release profile, absorption, distribution and elimination for the benefit of improving product efficacy and safety, as well as patient convenience and compliance. Most common methods of delivery include the oral, topical (skin), transmucosal (nasal, vaginal, ocular and rectal) and inhalation routes.
Example:-
o Almond Oil, Sweet, NF
o Corn Oil, NF
o Cottonseed Oil, NF
o Dextrose, Anhydrous, Granular, USP, EP, BP, JP
o Dextrose, Hydrous, Powder, USP
o Ethyl Oleate, NF
o Isopropyl Palmitate, NF
27. Wetting Agents:-
In pharmaceutical liquid dosage forms, surfactants often function as wetting agents, where they reduce interfacial tension. In lotions and sprays wetting agents help the preparation spread on the skin surface. In oral dosage forms they aid in creating a homogeneous dispersion of solid particles in a liquid vehicle. Surfactants are usually organic compounds that are amphiphilic, meaning they contain both hydrophobic groups (their tails) and hydrophilic groups (their heads). Therefore, a surfactant molecule contains both a water insoluble (or oil soluble) component and a water soluble component. Surfactant molecules will diffuse in water and adsorb at interfaces between air and water or at the interface between oil and water, in the case where water is mixed with oil. The insoluble hydrophobic group may extend out of the bulk water phase, into the air or into the oil phase, while the water soluble head group remains in the water phase. This alignment of surfactant molecules at the surface modifies the surface properties of water at the water/air or water/oil interface.
Example:-
o Benzalkonium Chloride, NF
o Benzethonium Chloride, USP
o Cetylpyridinium Chloride, Monohydrate, USP
o Docusate Sodium, USP
o Poloxamer 407, NF
o Poloxamer 188, NF
o Poloxamer 338, NF
o Polyoxyl 40 Stearate, NF
o Polysorbate 20, NF
o Polysorbate 40, NF
6. Reference:-
Excipient Development for Pharmaceutical, Biotechnology,and Drug Delivery Systems by Ashok Katdare,Informa Healthcare USA, Inc.
www.pharmagupshup.in
Excipient Master File Guide by Christopher C.DeMerlis,Pharmaceutical Technology, June 2002
Excipient Functionality by R. Christian Moreton, Pharmaceutical Technology, May 2004
USP 2007
IP 2007
http://en.wikipedia.org
https://www.spectrumchemical.com
http://www.britannica.com
Excipient interaction by Patrick, Pharmaceutical Technology, May 2004
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