A pharmaceutical excipient is any ingredient in a drug product other than the active pharmaceutical ingredient (API) used to aid in the manufacturing process but do not have a direct therapeutic effect.
INTRODUCTION
Many dosage forms formulated today are complex system containing many other components along with the active pharmaceutical ingredient (API); these compounds are generally added along with the active pharmaceutical ingredients in order to
- Protect, support or enhance stability of the formulation: Most of the times it is observed that the active pharmaceutical ingredient in its pure form does not retain its stability for long which results in its denaturation, or sticking to the container wall thus rendering it unfit, hence in order to stabilize the API pharmaceutical excipients are added which aid in maintaining the stability of the product and ensures that API retains its stability for a considerable period of time thus improving the shelf life of dosage formulation.
- Bulk up the formulation in case of potent drug for assisting in formulation of an accurate dosage form.
- Improve patient acceptance.
- Help improve bioavailability of active drug: – Excipients usually help in improving the bioavailability of the active pharmaceutical ingredient for e.g. In many cases an active substance (such as aspirin) is not absorbed easily by human body in such cases the active ingredient is dissolved in or mixed with a pharmaceutical excipient which may either act as solvent or assist in absorption of the drug in human body.
- Enhance overall safety and effectiveness of the formulation during its storage and use. These components are generally termed as pharmaceutical excipients and according to the international pharmaceutical excipient council, Pharmaceutical Excipient is defined as “Any substance other than active drug or pro-drug that is included in the manufacturing process or is contained in finished pharmaceutical dosage forms”. The US pharmacopoeia-National formulary (USPNF) categorizes excipients according to the functions they perform in the formulations e.g. Binders, disintegrants etc.
Excipient selection:
Pharmaceutical excipient selection:
- pharmaceutical excipient selection generally focuses on the desirable characteristics of excipients such as functionality, material consistency, regulatory acceptance, cost, availability, and sources.
- Material properties like micromeritics, chemical thermal rheological, mechanical etc also play an important role in development of drug formulation.
- Formulators must also consider physicochemical properties, stability and compatibility issue, pharmacokinetic attributes, permeation characteristics, segmental absorption behavior, drug delivery platform, intellectual property issues etc while selecting an pharmaceutical excipient for formulation development, this may help in determining the absorption challenges and desired delivery platform for active pharmaceutical ingredients.
The concept of quality by design (QbD) helps in understanding excipients normal variability and its potential impact on the processes of formulation development can be achieved. Pharmaceutical Excipient compatibility tests allows us to determine drug excipient interactions which can be either avoided or can be modified to utilize in an efficient manner which helps in minimizing the risk associated with the excipients. Pharmaceutical Excipient selection also depends on various routes of administrations.
Pharmaceutical excipient selection must be done on the basis of characteristics an excipient offers. The ideal characteristics of an excipient are given as under:-
An excipient must be:-
Chemically stable
Non-reactive
Low equipment and process sensitive
Inert to human body
Non toxic
Acceptable with characteristics
Economical regards to organoleptic
Having efficiency in regards with the intended use.
Categories
| Pharmaceutical excipient category | Function in formulation | Working principle | Examples |
| PHARMACEUTICAL EXCIPIENTS USED IN SOLID DOSAGE FORMS | |||
| Diluents | Fillers | Make up the bulk of solid unit dosage forms when drug itself is inadequate to produce the bulk. | Lactose, Directly compressible Starches, Dextrose, Sorbitol, Microcrystalline cellulose, Dibasic Calcium phosphate dehydrate. |
| Binders and Adhesives | Impart cohesive qualities to powdered material. | Improves free flow qualities by formulation of granules to desired hardness and size. | Acacia, Gelatin, Starch paste, Polyvinyl pyrrolidone, Glucose, Carboxymethyl cellulose, Povidone. |
| Lubricants | Reduce inter-particular friction, prevent adhesion of tablet material to the surface of dies and punches facilitate easy ejection of tablet from die cavity and improve the rate of flow tablet granulation | Interpose a film of low shear strength that interface between the tabletting mass and die wall | Talc, Stearic acid, Magnesium stearate, Calcium stearate, Polyethylene glycol, Surfactants, vegetable oil. |
| Glidants | Improve flow characteristics of powder mixture. | Added in dry state prior compression, it reduces friction between particles. | Colloidal Silicone dioxide (Carbosil), Asbestos free starch, Corn starch. |
| Disintegrants Superdisintegrants | Facilitate breakup or disintegration after administration Improved disintegrant efficacy resulting in decreased use levels when compared to traditional disintegrants | Function by drawing water into the tablet, swelling it and causing the tablet to burst apart. | Starches, Clays, Cellulose, Cross linked polymers, Modified starches such as Primogel and Explotab, Veegum HV. Crosscarmalose, Cross Povidone, Sodium starch glycolate. |
| Coloring agents ( these must be approved and certified by F.D.A) | Impart aesthetic appearance to dosage form, disguising off color drugs, product identification. | FD and C, D and C dyes and lakes. | |
| Flavors | Limited to chewable tablets/ tablets intended to dissolve in mouth. | Mask unpleasant taste | Spray dried and other flavors, syrups etc. |
| Sweeteners | Impart sweet taste to the formulation; use is limited to chewable tablets. | Mannitol, Saccharin.etc | |
| Sorbents | Moisture proofing | Limits the fluid sorbing, taking up of liquid or gas either by adsorption or absorption in dry state. | Silica gel, activated carbon, clay etc |
| Coating materials | Protect tablet ingredients from detoriation by moisture, help swallowing unpleasant tasting tablets | Hydroxypropylmethyl cellulose (HPMC), Synthetic polymers, Shellac, Corn protein Zein, Polysaccharides, Capslues coated by Gelatin, Povidone, Ethyl cellulose. | |
| Plasticizers | For soft gelatin capsule preparation, gelatin based suppositories, film coated tablets etc. | Produce elasticity and flexibility to the coating materials in case of tablets, determine hardness of capsule shell in case of soft gelatin capsule and impart softness and resilience to suppositories. | Castor oil, Diacetylated Monoglycerides, Polyethylene glycol, Polypropylene glycol, Triacetin. |
| PHARMACEUTICAL EXCIPIENTS USED IN LIQUID DOSAGE FORMS | |||
| Solvents. Co solvents | Dissolving solute/Active pharmaceutical ingredient. Increase the solubility of solute in solvents. | Breaking of bonds and reducing effective charge on ions thus increasing Solute-Solvent forces of attraction which are eventually greater than Solute-Solute and Solvent-Solvent forces of attraction. Co-solvent system works by reducing the interfacial tension between predominantly aqueous solutions and hydrophobic solutes. | Water, alcohol, acetic acid, acetone, ethyl acetates, syrups, etc. Ethanol, Sorbitol, Glycerin, Propylene glycol etc. |
| Buffers | Maintain pH of the formulation. | Act by binding hydrogen ions in acids and donating hydrogen ions in bases | Phosphate buffers, Acetate buffers, Citric acid Phosphate buffers etc |
| Antimicrobial preservatives. | Prevent microbial growth in formulations. | Bacteriostatic action | Benzyl alcohol, Butyl paraben, Phenol, Thiomersal etc. |
| Antioxidants | Control oxidation. | Act by getting preferentially oxidized or by blocking an oxidative chain reaction. | Ascorbic acid, Sodium bisulphate, Thiourea, Butyl Hydroxy Toluene (BHT), Tocopherols.etc |
| Wetting agents | Aid wetting and dispersion of hydrophobic active pharmaceutical ingredients. | Act by reducing interfacial tension between solids and liquids in suspensions. | Sodium Lauryl Sulphate (SLS), Tween 80, Spans, Lecithins etc. |
| Antifoaming agents | Discourage formation of stable foam. | Lowers surface tension and cohesive binding of liquid phase. | Simethicone, Organic phosphates, Alcohols, Paraffin oils, Sterates and glycols. |
| Thickening agents. | Prevent settling/sedimentation, modify viscosity. | Work by entrapment of solid particles. | Methyl cellulose, Hydroxyethyl cellulose, Microcrystallince cellulose etc |
| Humectants | Retard evaporation of aqueous vehicles from dosage forms | They are hygroscopic in nature which helps in preventing evaporation of solvent. | Propylene glycols, Glycerol, Polyethylene glycol etc. |
| Chelating agents. | Protect drug from catalysts that accelerate the oxidative reaction. | Chelating agents form complexes with metal ions inactivating their catalytic activity in oxidation of medicaments. | Disodium EDTA, Dihydroxy ethyl glycine, Citric acid and Tartaric acid. |
| Emulsifying agents | Prevent coalescence of the dispersed globules. | Forms barriers at interface, and reduces interfacial tension. | Sodium Lauryl Sulphate, Cetrimide, Macrogol esters, Sorbitan esters etc. |
| Flocculating agents. | Prevent caking | Addition of an electrolyte reduces the magnitude of zeta potential of dispersed particles | Starch, Sodium alginate, Carbomer.etc. |
| Sweetening agents | Impart sweetness | Sucrose, Sorbitol, Saccharin, Aspartame, Sucralase | |
| Colors | Impart color | Amaranth, Erythrosin, Eosin, Tartarazine etc. | |
| Flavors | Impart flavor | Aromatic waters, Syrup etc | |
| Excipient used in aerosol Propellant | Developing pressure in container which expels the product | Trichloromonofluoromethane, Dichlorodifluoromethane, Etc. | |
| PHARMACEUTICAL EXCIPIENTS USED IN SEMI-SOLID DOSAGE FORM | |||
| Structure forming excipients | Form gel like structure | Cetosterly alcohol, sorbiton and other hydrophilic surfactants, fluid hydrocarbons like mineral oils etc | |
| Preservatives | For preserving the formulation | Benzyl alcohol, proply paraben, methyl paraben, chlorocresol, imidazolidinyl urea, sodium benzoate etc | |
| Antioxidants | Prevent oxidation | Butyl hydroxy toulne , butyl hydroxy anisole, ascorbic acid etc | |
| Solubilizers | Enhance solubility of the active | Lanolin, cholesterol or cholesterol esters | |
| Gelling agents | Form gels | Carbomer934, pemulen®, carboxy methyl cellulose, hydroxy propyl cellulose, xanthan gum etc | |
| Emollients | Modify vehicle/skin characteristics to assist penetration of active ingredient through skin | Glycerin, mineral oil, petrolatum, isopropyl palmitate etc | |
| suppository bases | Used to form base for dissolving active ingredient | Cocoa butter, glycerin, coconut oil, gelatin, hydrogenated vegetable oil, polyethylene glycol etc | |