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Excipients Used in Pharmaceutical Compounding

Preparations require excipients to impart a variety of properties to the compounded . From the compounder’s viewpoint, it is prudent to understand the role of each ingredient in the completed preparation. Many times this insight may alert the compounder to potential instabilities that might occur, clues about the preparation’s performance that would be useful/necessary to share with the patient, or provide alternatives if the preparation is not suitable for a patient due to allergies, preferences, etc. Also, excipients have different roles in different preparations, or oftentimes an excipient will play more than one role in a preparation. The list below is a compilation from several reference sources. It is not an all-inclusive list, nor does it provide an absolute classification scheme for all the excipients used in compounded preparations. It does serve as a basic template that can be expanded as desired.

INGREDIENT TYPE DEFINITION EXAMPLES

Acidifying agent Provides acidic medium for product stability in preparations. Acetic acid Fumaric acid Hydrochloric acid Nitric acid Alkalinizing agent Provides alkaline medium for product stability in Ammonia liquid preparations. Ammonium carbonate Diethanolamine Monoethanolamine Potassium Sodium bicarbonate Sodium borate Sodium carbonate Sodium hydroxide Trolamine Adsorbent Holds other molecules onto its surface by physical or Powdered chemical (chemisorption) means. Activated charcoal

Aerosol propellant Develops pressure within an aerosol container, which Carbon dioxide expels the ingredients when the valve is opened. Dichlorodifluoromethane Dichlorotetrafluoroethane Trichloromonofluoromethane Air displacement Displaces air in a hermetically sealed container to enhance product stability. Carbon dioxide Antifoaming agent Breaks up and inhibits the formation of foams. Dimethicone Lauric acid NF32 Myristic acid Palmitic acid Simethicone Antifungal Prevents growth of fungi in liquid and semisolid Butylparaben preparations. Use in combination usually enhances Ethylparaben the effectiveness of . Methylparaben Benzoic acid Propylparaben Sodium benzoate Sodium propionate preservative Prevents growth of in liquid and Benzalkonium chloride semisolid preparations. Methylparaben Propylparaben Sorbic acid Prevents deterioration of preparations by oxidation. Ascorbic acid Ascorbyl palmitate Butylated hydroxyanisole Butylated hydroxytoluene Hypophosphorous acid Monothioglycerol Propyl gallate Sodium ascorbate Sodium bisulfite Sodium formaldehyde sulfoxylate Sodium metabisulfite Buffering agent Resists change in pH upon dilution or addition of Potassium metaphosphate acid or alkali. Potassium phosphate, monobasic Sodium acetate Sodium citrate, anhydrous and dihydrate Chelating agent Substance that forms stable -soluble complexes Edetic acid (chelates) with metals; used in some liquid Edetate disodium pharmaceuticals as stabilizers to complex heavy metals that might promote instability. In such use, they are also called sequestering agents. Clarifying agent Filtering aid used for its adsorbent qualities. Bentonite Talc Colorant Imparts color to liquid and (e.g., tablets and FD&C Red No. 3 capsules) preparations. FD&C Red No. 20 FD&C No. 6 FD&C No. 2 D&C Green No. 5 D&C Orange No. 5 D&C Red No. 8 Caramel Ferric oxide, red Emollient Softens the skin or soothes irritated skin or mucous Acetylated lanolin membranes. Cetyl acetate Cetyl lactate Cetyl ricinoleate Disopropyl adipate Disopropyl dimerate Glyceryl oleate Hexylene glycol Isopropyl isostearate Isopropyl palmitate Isostearic acid derivatives Maleated soybean Myristyl myristate Octyl dodecanol Octyl hydroxystearate Octyl palmitate Phenyl trimethicone Tocopheryl acetate Tocopheryl linoleate Triisocetyl citrate Wheat germ Emulsifying agent Promotes and maintains of the finely Acacia subdivided particles of liquid in vehicles where it is Agar immiscible. Liquid emulsion or semisolid emulsion Behenoyl Polyoxylglycerides may be the end product. Benzalkonium chloride Benzyl benzoate Caprylic acid Caprylocaproly - Polyoxylglycerides Carbomer Copolymer Carbomer Homopolymer Cetomacrogol Cetyl alcohol Glyceryl monostearate Sorbitan monooleate Polyoxyethylene 50 stearate (myrj23) Encapsulating agent Forms thin shells in which is enclosed to ease administration. barrier on tablets meant to prevent Cellulose acetate phthalate from breaking down in the stomach, (35% in alcohol, pharmaceutical glaze) instead allowing breakdown in the . Film coating Polymer coating applied to tablets meant to protect Hydroxyethyl cellulose the dosage form or modify its release. Hydroxypropyl cellulose Hydroxypropyl methylcellulose (Hypromellose) Methylcellulose (e.g., Methocel) Ethylcellulose (e.g., Ethocel) Flavorant Gives a pleasant and often odor to a oil preparation. Synthetic flavorants may also be used in Cinnamon oil addition to the natural flavorants listed. Cocoa Menthol Orange oil Peppermint oil Vanillin Flavoring/sweetening agent Imparts a pleasant flavor and sweetness to a Acacia preparation. Aromatic syrup Aromatic syrup Cocoa syrup Orange syrup Syrup Foam adjuvant Improves the stability and reduces the specific Arachidic acid gravity of foam. It may increase the foaming capacity Arachidyl alcohol of . Behenic acid Behenyl alcohol Cetyl alcohol Hexadecanoic acid Octacosanoic acid Stearyl alcohol Amphiphilic substance that facilitates the formation Brij 38 of foam. Brij 52 Brij 56 Isoceteth-20 Laureth-4 Myrj 45 Myrj 49 Myrj 59 Polyglyceryl-4 isostearate Polyoxyethylene (20) sorbitan monostearate (Tween 60) Polyoxyethylene (2) sorbitan monooleate (Tween 80) Sodium lauryl sulfate Sorbitan laurate Sorbitan monolaurate Sorbitan palmitate lauryl sulfate Gelling agent Increases the of a substance; can act as a Acrylic acid/ethyl acrylate copolymers stabilizer. Carboxyvinyl gum Egg albumin Gelatin agar Hydroxyethyl cellulose Hydroxypropyl guar gum Hydroxyl propylmethyl cellulose Polymethacrylic acid polymers Polyvinyl alcohol Locust bean gum Quince seed extract Sodium alginate Sodium caseinate Tragacanth gum Humectant Prevents drying of preparations, particularly Glycerin ointments and . Propylene glycol Hydrophilic Liquid with high with water, used to Azone dissolve solutes. Caprylic acid Diethylene glycol Dimethylacetamide Dimethylformamide Dimethylsulfoxide Dioxolane Di-terpenes Ethylene glycol Glycerin Hexylene glycol Lauric acid Lauryl alcohol Lemonene l-menthol Myristyl alcohol Polyethylene glycols Propylene glycol Terpeneol Terpenes Hydrophobic solvent Liquid with low or no miscibility with water, used to Borage seed oil dissolve solutes. Canola oil Cod-liver oil Corn oil Cottonseed oil Docosahexaenoic acid Eicosapentaenoic acid Evening primrose Flaxseed oil Gamma-linoleic acid Linoleic acid Linolenic acid Olive oil Omega-3 and omega-6 fatty acids Salmon oil Sesame oil Some essential oils Soybean oil Sunflower oil Triglyceride oil Wheat germ oil Levigating agent Liquid used as an intervening agent to reduce the Mineral oil particle size of a by grinding, usually in a Glycerin mortar. Propylene glycol

Ointment base Semisolid vehicle for medicated ointments. Lanolin Hydrophilic ointment ointment Petrolatum Hydrophilic petrolatum ointment Yellow ointment Rose water ointment pH Modifier (Acidifying Decreases or increases pH in preparations or protects Acetic acid agent/Alkalizing compounds from rapid change in pH. Acetic acid, glacial agent/Buffering agent) Adipic acid Ammonia solution, strong Ammonium carbonate Ammonium chloride Ammonium phosphate Boric acid carbonate Calcium lactate Calcium phosphate, tribasic Citric acid, monohydrate Citric acid, anhydrous Diethanolamine Fumaric acid Glycine Hydrochloric acid Hydrochloric acid, diluted Alpha-lactalbumin Lactic acid Lysine hydrochloride Maleic acid Monoethanolamine Monosodium glutamate Nitric acid Phosphoric acid Phosphoric acid, diluted Potassium bicarbonate Potassium citrate Potassium hydroxide Potassium metaphosphate Potassium phosphate, dibasic Potassium phosphate, monobasic Propionic acid Racemethionine Sodium acetate Sodium bicarbonate Sodium borate Sodium carbonate Sodium citrate Sodium hydroxide Sodium lactate solution Sodium phosphate, dibasic Sodium phosphate, monobasic Succinic acid Sulfuric acid Tartaric acid Trolamine

Plasticizer Component of film-coating to make film Diethyl phthalate more pliable, enhance spread of coat over tablets, Glycerin beads, and granules. Solvent In preparation of a solution, aqueous or oleaginous Alcohol solvent may be used to dissolve another substance. Bacteriostatic Sodium Chloride Water and hydroalcoholic alcohol, water and glycerin Corn oil may be used as co- when needed. Sterile Cottonseed oil solvents are used in preparations such as injections. Glycerin Isopropyl alcohol Mineral oil Peanut oil Purified water Water for Injection Sterile Water for Injection Sterile Water for Irrigation Stiffening agent Increases thickness or hardness of a preparation, Cetyl alcohol usually an ointment. Cetyl Microcrystalline wax Paraffin Stearyl alcohol White wax Yellow wax coating Sweetened outer layer on oral solid dosage forms. Liquid glucose base Vehicle for . Cocoa Polyethylene glycols (mixtures) PEG 3350 (surface-active Substances that absorb to surfaces or interfaces to Benzalkonium chloride agent) reduce surface or interfacial tension. May be used as Nonoxynol 10 wetting agents, , or emulsifying agents. Octoxynol 9 Sodium lauryl sulfate Sorbitan monopalmitate Suspending agent Viscosity-increasing agent used to reduce Agar rate of particles in a vehicle in which Bentonite they are not soluble; may be formulated Carbomer (e.g., Carbopol) for oral, parenteral, ophthalmic, topical, or other Carboxymethylcellulose sodium route. Hydroxyethyl cellulose Hydroxypropyl cellulose Hydroxypropyl methylcellulose Kaolin Methylcellulose Tragacanth Veegum Sweetening agent Gives sweetness to a preparation. Dextrose Glycerin Saccharin sodium Sorbitol Sucrose anti-adherent Prevents tablet ingredients from sticking to punches stearate and dies during production. Tablet binder Substances that cause adhesion of powder particles in Acacia tablet granulations. Alginic acid Carboxymethylcellulose sodium Compressible sugar (e.g., Nu-Tab) Ethylcellulose Gelatin Liquid glucose Methylcellulose Povidone Pregelatinized starch Tablet and diluent Inert filler that creates desired bulk, flow properties, Dibasic calcium phosphate and compression characteristics of tablets and Kaolin capsules. Mannitol Microcrystalline cellulose Powdered cellulose Precipitated Sorbitol Starch Tablet direct compression For use in direct compression tablet . Dibasic calcium phosphate (e.g., Ditab) excipient Tablet disintegrant Promotes disruption of the mass in a solid form into Alginic acid smaller particles that are more easily dispersed or Polacrilin potassium (e.g., Amberlite) dissolved. Sodium alginate Sodium starch glycolate Starch Tablet glidant Improves flow of properties of the powder in Colloidal silica tablet and capsule formulations. Cornstarch Talc Tablet lubricant Reduces of tablet formulations during tablet Calcium stearate compression. Magnesium stearate Mineral oil Stearic acid Zinc stearate Tablet or capsule opaquant Renders a coating opaque when used alone or with a Titanium dioxide colorant. Tablet polishing agent Gives an attractive sheen to coated tablets. White wax Tonicity agent Makes a solution similar in osmotic dextrose Sodium chloride characteristics to physiologic fluids, such as irrigation, ophthalmic, and parenteral fluids.

Vehicle A base used in a variety of for oral and parenteral administration. Oral liquids are aqueous (e.g., ) or hydroalcoholic (e.g., ). Solutions for intravenous use are aqueous, whereas intramuscular injections may be aqueous or oleaginous. Viscosity-increasing agent Renders preparations more resistant to flow. In Alginic acid suspensions sedimentation is deterred, contact time is Bentonite enhanced in ophthalmic solutions (e.g., Carbomer methylcellulose), and topical creams are thickened. Carboxymethylcellulose Sodium Methylcellulose Povidone Sodium alginate Tragacanth Water-miscible co-solvent Increases the solubility of poorly water soluble substances or enhances the chemical stability of a Glycerin drug. Isopropanol Polyethylene glycol Propylene glycol Water-repelling agent Hydrophobic material used as a non-sticky lubricant Cyclomethicone in in creams or as an enhancer and stabilizer Dimethicone in foams. Simethicone Wetting and/or solubilizing Reduces the of water, allowing it to Betadex Sulfobutyl Ether Sodium agent spread more easily, and/or improves the solubility of poorly water soluble .

Adapted from:

“Dosage Form Designs: Pharmaceutical and Considerations,” by L. V. Allen, Jr. and H. C. Ansel, chap. 4 in Ansel’s Pharmaceutical Dosage Forms and Systems, 10th ed. (Baltimore: Lippincott Williams & Wilkins, 2012): 102–165.

Excipients: USP and NF Excipients, Listed by Functional Category: USP−NF Online. (Rockville, MD: United States Pharmacopeial Convention, 2014).

, , and pH,” by L. V. Allen, Jr., Secundum Artem 18, no. 1: 1–8. Available online. URL: http://www.perrigo.com/business/education.aspx.

“Foam Dosage Forms,” by L.V. Allen, Jr. International Journal of Pharmaceutical Compounding 17, no. 4 (2013): 312–322.

USP–NF Chapter <1059> Excipient Performance: USP−NF Online. (Rockville, MD: United States Pharmacopeial Convention, 2014).