Formulation of parenteral
It consists of following:
Vehicles:
• Aqueous
• Non- aqueous
Additives:
• Solubilising agents
• Stablizers
• Buffers
• Preservatives
• Chelating agents
• Tonicity factors
• Suspending agents, emulsifiers and wetting agents
Vehicles:
These are added in parenteral preparations to dissolve or disperse drug and to deliver it to the site of action. There are two types of vehicles which are used in preparation of parenteral:
Aqueous vehicle:
Water is used as vehicle for most of the preparations because it is well tolerated by the body and safest to administer.
The aqueous vehicles used are:
• Water for Injection
• Sterile Water for Injection
• Bacteriostatic water for injection
Water for injection:
It must be free from pyrogen free but not necessary that it is sterile. It is obtained by deionsation and distilled water. It should have not more than 1mg/100ml of total solids.
Sterile water for injection:
It is water for injection which must be pyrogen free and sterile. It is packed in single dose container having a volume less than 1 litre. It does not contain any antimicrobial agent.
Bacteriostatic water for injection:
It is sterile water for injection having one or more antimicrobial agents. It is packed in multiple dose container so that repetitive water withdrawn from container can be possible without contamination. Volume does not exceed more than 5ml since bacteriostatic agents are toxic if used in large concentrations.
Non – aqueous vehicle:
These are used due to following reasons:
• To increase the solubility of water insoluble drugs
• To protect the drugs which undergo hydrolysis.
The mostly used non- aqueous vehicle are:
Water miscible vehicles:
Water miscible solvents are used along with main solvent in parenteral preparation. These are used to increase solubility of certain drugs in an aqueous vehicle or to decrease the hydrolysis of drugs.
Example:
• Ethyl alcohol in preparation of hydrocortisone injection.
• Propylene glycol in preparation of digoxin injection.
Water immiscible vehicles:
Fixed oils such as arachis oil, almond oil and sesame oil etc used as vehicle. These are used generally when depot action of formulation is needed or drug is insoluble in water.
Example:
• Dimercaprol injection using arachis oil as vehicle.
Additives:
• These agents are used to increase the stability or quality of the product.
• These agents are used to increase solubility of drug in desired solvent.
• These agents are used to make formulation isotonic with blood plasma.
• These are used to maintain sterility in the formulation.
• These agents should be physically and chemically compatible with formulation.
Solubilising agents:
• These are the agents which increase solubility of the drug into solvent. The solubilizing agents may be of two types:
• Surfactants
• Co-solvents
Surfactants: These agents increase the solubility of the drug into solvent by reducing the surface tension of the drug. Example: Tween 80 (polyoxyethylene sorbitan monooleate), Tween 20 (polyoxyethylene sorbitan monolaurate), Lacithin etc.
Co-solvents: These are the solvents which are used in conjunction with another solvent to dissolve the drug. Example: Propylene glycol, glycerin, ethanol, polyethylene glycol, sorbitol etc.
Stabilizers:
• These are the agents which prevent oxidation and hydrolysis of the formulation.
• E.g. Ascorbic acid (0.02 – 0.1%), Thiourea (0.005%), Sodium metabisulfite ( 0.1 – 0.15%)
Buffers:
• These are the agents which resist change in pH of formulation or increase the solubility of drug in solution.
• E.g. Acetic acid (1-2%), Citric acid (1-5%), Phosphoric acid (0.8-2%)
Preservatives:
• These are the agents which prevent the growth of microbes in the formulation. These are added in multiple dose containers to prevent the contamination of content due to repeated withdrawn of the content. Large volume, single dose container does not have preservative.
• E.g. Phenol (0.065 – 0.5%), Benzyl alcohol (0.5 – 10%), Thimerosal (0.001 – 0.2%)
Chelating agents:
• These agents are used to form chelates with the metallic ions present in the formulation an hence prevent the drug degradation.
• Example: Oxidation of adrenaline by copper, iron etc which can be avoided by use of EDTA (Ethylene diamine tetra acetic acid), disodium edetate etc. in concentration of 0.05%.
Suspending agents:
• These agents are used to increase the viscosity and to suspend the particles for a long time.
• E.g. Gelatin (2%), Methylcellulose (0.03 – 1.05%), Pectin (0.2%)
Emulsifiers:
• These are the agents which are used in sterile emulsions to make miscible.
• E.g. Lecithin (0.5 -2.3%), Polysorbate 80.
Wetting agents:
• These are the agents which are used to prevent the interfacial tension between solid and liquid phase.
• E.g. Propylene glycol ( 0.2 – 50%), Polysorbate 80 ( 0.04 – 0.4%)
Tonicity factors:
• These are the agents which are used to make preparation isotonic with blood plasma or other tissue fluid.
• E.g. Lactose (0.14 – 5%), Mannitol (0.4 – 2.5%), Sorbitol (2%), sodium chloride (0.9%)
