Manufacturing considerations:

Manufacturing of a sterile suspension is a complicated process that typically requires –
The sterilization and milling of the active ingredient (s)
Sterilization of the vehicle system
Aseptic wetting and dispersion of the active ingredient (s)
Milling the bulk suspension
Aseptic filling of the bulk suspension into suitable sterile containers

Basic methods which are applied to sterilize the solids for injectable suspensions are –
Re-crystallization
Spray drying
Lyophilization
Ethelyne oxide gas
Dry heat and
Gamma radiation



1. Re-crystallization
The hydrophobic active ingredient (s) is dissolved in an organic solvent. Then the drug solution is sterilized by filtration. A sterile ‘counter’ solvent is aseptically added to the sterile drug solution to generate the sterile crystalline material. The crystals are aseptically collected, washed, dried to remove residual solents and milled to the appropriate particle size.
Advantage: The method is weconomical.
Disadvantage: aseptic amanipulation is required and the choice of solvents is limited.
Commonly used solvents are – acetone, CHCl3 and CH2Cl2.

2. Spray drying:
The active ingredient (s) is dissolved in a solvent, filtered through a sterilizing filter, sprayed into a spray drying chamber and exposed to extremely high heat for a very short interval to yield a sterile dry powder. It forms hollow spheres of uniform size.
Advantages: Milling is not required here. It is applicable for heat liable materials.

3. Lyophilization (freeze drying):
It is a technique for removing a solvent from solution of heat liable materials. The process yields solid material with high surface area that is readily reconstituted upon addition of solvent. A sterile solution containing the active ingredient is frozen by lowering the temperature of the solution below its characteristic eutectic temperature. The solvent is then removed by sublimation (by using controlled application of vacuum and temperature), thus leaving a dry powder or cake.

Advantages:
To maintain accurate dose of high surface area solid
To increase stability
To prepare pharmaceutically elegant product
To reduce transportation cost
To minimize interaction between product and packaging ingredient and
To minimize potential for particulate development

Disadvantages:
Time consuming for processing
Milling results possible formation of light friable or dense hard materials
Costly set-up is required
Labor cost

4. Sterilization:
(a) Gaseous sterilization (by ethylene oxide): for previously milled materials, it requires 2-4 hrs exposure time depending on the gas composition, temperature ranging form 50-600c and the RH approximately is 70%.
Precaution: after sterilization by it the level of ethylene oxide, ethylene glycol and chlorohydrine residues should be monitored. The occupational health and safety administration has changed personal Eto exposure limits from 50-0.5ppm.

(b) Dry heat sterilization: previously milled material is generally exposed to heat above 1400c for various time periods depending on temperature.
Advantages: easiest and safest method for sterilization.
Disadvantages: not suitable for volatile and heat sensitive materials.

(c) Sterilization by radiation therapy: e.g. – gamma radiation, the primary source used for gamma irradiation is cobalt 60. For stability conformance, the preliminary experiment should be conducted.
Advantages:
to sterilize the bulk drugs and/or and finished products
relatively low temperature is required
no residual mater is deposited in the product
maximum sterility assurance is achieved
Disadvantages: it can cause physical and chemical degradation of product and /or packaging materials.