Sterilization

Sterilization

All parenteral products must be sterile. Sterility is assured by a three-step process: (1) use of sterile starting materials and process equipment; (2) use of special technique in drug product manufacture that minimizes the possibility of contamination from human or extraneous material during manufacture; and (3) sterilization postmanufacture, preferably in final marketed sealed containers. The are several methods of sterilization for par-enteral products, including dry heat, steam, filtration, gas, and radiation.

Filtration

Sterilization by filtration is a process that removes, but does not destroy, microorganisms. Filtration is the method of choice for solutions that are unstable to other types of sterilizing processes, for example, thermolabile products. Membrane filters of 0.22 μm pore size are commonly used as sterilizing filters. However, macromolecules, such as proteins and peptides, may be damaged by filtration due to shear stress, leading to alteration in their three-dimensional structure. In certain cases, formulation might affect filter integrity and clogging. In addition, some filters adsorb drug. Therefore, drug interactions with filter materials are carefully investigated before implementing this method of sterilization. Common filter materials include nylon and teflon.

Dry heat sterilization

Dry heat sterilization is the simplest and most economical method of steril-ization. However, this method requires higher temperature (~160°C–250°C) and longer exposure (~30–180 min) to achieve sterility. A major problem associated with dry heat sterilization is nonuniform distribution of tem-perature. Furthermore, dry heat sterilization cannot be used with materials that are heat sensitive. It is mainly used for sterilization of glass- and metal-processing equipment.

Steam sterilization (autoclaving)

Steam sterilization is carried out in an autoclave, which is an airtight jack-eted chamber designed to maintain a high pressure of saturated hot steam, with the typical temperature of 121°C. Steam sterilization is the method of choice for sterilization of aqueous solutions, glassware, and rubber articles. However, steam sterilization cannot be used with materials that are heat sensitive or nonaqueous formulations.

Radiation sterilization

Radiation sterilization is accomplished by exposure to ultraviolet (UV) light or high-energy ionizing radiation. UV radiation is useful in reducing the number of airborne microorganisms. Microorganisms are often killed by using β-rays, γ-rays, X-rays, and accelerated electron beams. Thermolabile drugs, such as penicillin, streptomycin, thiamine, and riboflavin have been effectively sterilized by ionizing radiation. However, the retail and hospital pharmacists have little opportunity to use radiation sterilization.