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Formulation of sterile powders, Injections or lyophilized products:

Formulation of Injections:

These are sterile solutions or suspensions of drugs in aqueous or oily vehicle meant for administration into the body by means of a needle under or through one or more layers of skin. The formulation of injections is same as that of formulation of parenteral products hence refer formulation of parenteral products.

Formulation of sterile powders or lyophilized products:
Drugs which are not stable in solution form are prepared as dry sterile solids which are dissolved in water for injection just before administration. Example: Cefuroxime sterile powder. Sterile water for injection is supplied with dry powders to make solution or suspension for injection. It can be given by IV or IM route but suspension is not given by IV route.

Methods of preparation of sterile powder:
Sterile recrystallization:
The drug is dissolved in a solvent and obtained solution is sterilized through membrane filter having pore size 0.22µ. A sterile anti-solvent is then added to crystallize the drug particles followed by filtration and drying aseptically.

Lyophilization:
It is a process of separating a solid substance from solution by freezing the solvent and evaporating the ice under vacuum. In this, drug solution is sterile filtered into the sterile trays, which are placed in freeze dryer at temperature -50°c and then dried by vacuum to separate the drug powder.

Spray drying:
The solution of drug is sprayed into a dry chamber where it comes in contact with a hot steam of a sterile gas (80-100°c).

Formulation:
Fillers or bulking agents:
These are used to make the sufficient structure of the cake after drying or to make up the volume of the cake. These are used when the dose of the drug is too small or when it is less than 2%. Example:
Mannitol, glycine, glucose, sucrose, dextran etc.

Buffering agents:
These are the agents which are used to resist the change in pH of the product. Example: sodium citrate, sodium phosphate, sodium hydroxide etc.

Collapse temperature modifiers:

These are the agents which increase the collapse temperature. During lyophilization process, the primary drying temperature should be below than collapse temperature otherwise drying timing increases.
Example: Dextran, Ficoll, gelatin etc.

Tonicity modifiers:
These are the agents which make formulation isotonic with blood plasma. Example: Dextrose, sodium chloride etc.

Antimicrobial agents:
These are the agents which prevent the growth of microbes in formulation. These are generally added in multi-dose containers. Example: Ethyl and methyl paraben, phenol, cresol etc.

Solubilizing 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.

Complexing agent:
• These agents are used to form Complex with the metallic ions present in the formulation an hence prevent the drug degradation.
Example: EDTA (Ethylene diamine tetra acetic acid), disodium edetate etc. in concentration of
0.05%.

Lyophilization and lyophilized products:

Lyophilization is a process in which water is frozen, followed by removal from the sample, initially by sublimation and then by desorption. In this process, moisture content of the product is decrease to such an extent that it does not cause microbial growth. This process has following steps:

Freezing:
This step involves the freezing of sample solution at -50°c.

Primary drying:
In this, frozen ice is sublimed and dry and structurally an intact product is formed. This is the most time consuming step in this process.

Secondary drying:
In this step, after primary drying the residual moisture content is reduced by continuing the drying at slow rate.

Formulation of small volume parenteral:
These are the parenteral preparations administered in less than 100ml. Formulation of small volume parenteral is same as that of injections hence refer formulation of injections.
Types of small volume parenteral:
• Ampules
• Vials
• Prefilled syringes


Ampules:
• These are single dose containing small volume parenteral.
• These are glass containers with an elongated neck that must be broken off.
• Most of the ampules are weakened around the neck for easy breaking off the ampules and some ampules have colored bend around the neck.
• Whole formulation in ampule is used at once.

Vials:
• These are multi dose containing small volume parenteral
• These are made up of glass or plastic and sealed with rubber stopper.
• A needle is used to add contents and withdraw the formulation in vials.
• A portion of formulation is withdrawn from vial at one time and remaining portion in vial can be used again.
• Vials may be single dose containing and multi dose containing.
• Multi dose containing vials have preservative to prevent the bacterial contamination.