Formulation and packaging-sterile products

It is quite rare that the composition or the packaging of an ophthalmic pharmaceutical will lend itself to terminal sterilization, the simplest form of manufacture of sterile products. Only a few ophthalmic drugs formulated in simple aqueous vehicles are stable to normal autoclaving temperatures and times (121°C for 20-30 min). Such heat-resistant drugs may be packaged in glass or other heat-de-formation-resistant packaging and thus can be sterilized in this manner. The convenience of plastic... 

Inhalation solution and suspension drug products are typically aqueous-based formulations that contain therapeutically active ingredients and can also contain additional excipients. Aqueous-based oral inhalation solutions and suspension must be sterile (21 CFR 200.51). Inhalation solutions and suspensions are intended for delivery to the lungs by oral inhalation for local or systemic effects and are used with a specified nebulizer. Unit-dose presentation is recommended for these drug products to prevent microbial contamination during use. The container closure system for these drug products consists of the container and closure and can include protective packaging such as foil overwrap. 

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. 

USP Type III has been found acceptable in packaging some dry powders that are subsequently dissolved to make a buffered solution and for liquid formulations that prove to be insensitive to alkali. Type III glasses are usually not used for those products that are sterilized in their final container. Type II glass containers can be dry heat sterilized and filled under aseptic conditions. 

SVI formulations are relatively simple, composed of the active ingredient, a solvent system (preferably aqueous), a minimal number of excipients present for reasons described later in this chapter, and the appropriate container and closure packaging system. If the active ingredient is unstable in solution or suspension, the product can be a dry powder, processed either by lyophilization or by sterile crystallization. 

---