Process design sterile formulations

Although very important research and development (R D) means are dedicated to applications of supercritical fluids (SCFs) in the pharmaceutical industry, a very limited number of commercial plants are now operating or under construction and few companies have acquired some know-how in process scale-up, especially in SCF formulation and particle design, in compliance with the constraints imposed in this industry [traceability and General Manufacturing Processes (GMP), sterility, etc]. 

The objectives of the process design and optimisation stages of product development have been discussed in chapter 8, Product Optimisation . For ophthalmic products, like parenterals, process development can be quite challenging because the formulation must be manufactured sterile. Quite often, it is discovered that some formulations cannot withstand a stressful sterile process such as autoclaving. Chemical degradation or changes to the formulation properties of multiphase systems, such as suspensions and gels, can occur. In all cases, the compendial sterility test requirements described in the various pharmacopoeias must be complied with. 

Sterilization of the finished drug delivery formulation is an important consideration often overlooked in the early design of lactide/glycolide delivery systems. Aseptic processing and terminal sterilization are the two major routes of affording an acceptably sterile product. Both of these methods are suitable for products based on lactide/glycolide polymers if proper care is exercised in processing or selection of the treatment procedures. 

The production of sterile products is profoundly impacted both by formulation and the selection of primary packaging components. Design parameters for a facility and selection of appropriate manufacturing technologies for the product require that the formulation process and packaging components be chosen and evaluated in advance. 

Once the materials have been sterilized, interventions near either the formulation or product contact surfaces/parts should be minimized. Direct handling of these materials should only be done with sterilized tools or implements nonsterile objects, such as operator gloves, should never directly contact a sterilized surface. Sampling, filter integrity testing, process connection, and other activities should all be designed to eliminate the need for personnel exposure to sterile items. 

Distilled water is often used in the formulation of oral and topical pharmaceutical preparations and a low bacterial count is desirable. It is also used after distillation with a specially designed still, often made of glass, for the manufacture of parenteral preparations and a post-distillation heat sterilization stage is commonly included in the process. Water for such preparations is often stored at 80°C to prevent bacterial growth and the production of pyrogenic substances which accompany such growth. 

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