ABSTRACT
Dry granulation is an indispensable process used to improve the flow property of moisture-sensitive materials. Considering the limitations of currently available dry granulation techniques, it is necessary to develop a novel technique. In this study, a twin-screw dry granulation (TSDG) technology was successfully applied to produce a sustained-release dry granule formulation, which was subsequently compressed into sustained-release tablets. Based on a preliminary study, theophylline was selected as model drug, Klucel™ EF, Ethocel™, and magnesium stearate were selected as excipients. A Resolution V Irregular Fraction Design was applied to determine the effect of different processing parameters (screw speed, feeding rate, barrel temperature, and screw configuration) on product properties (flow properties, particle size distribution, and dissolution time). A reliable model was achieved by combining the data obtained, and processing parameters were automatically optimized to attain the setting goal. In general, TSDG was demonstrated to be an alternative method for the preparation of dry granules. The continuous processing nature, simplicity of operation, and ease of optimization made TSDG competitive compared with other conventional dry granulation techniques.
Subject(s)
Desiccation/methods , Drug Compounding/methods , Excipients/chemistry , Theophylline/chemistry , Chemistry, Pharmaceutical/instrumentation , Chemistry, Pharmaceutical/methods , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacokinetics , Desiccation/instrumentation , Drug Compounding/instrumentation , Drug Liberation , Feasibility Studies , Particle Size , Solubility , Tablets , Temperature , Tensile Strength , Theophylline/pharmacokineticsABSTRACT
This review gives a brief overview about microbial contamination in pharmaceutical products. We discuss the distribution and potential sources of microorganisms in different areas, ranging from manufacturing sites, pharmacy stores, hospitals, to the post-market phase. We also discuss the factors that affect microbial contamination in popular dosage forms (e.g., tablets, sterile products, cosmetics). When these products are contaminated, the microorganisms can cause changes. The effects range from mild changes (e.g., discoloration, texture alteration) to severe effects (e.g., changes in activities, toxicity). The most common method for countering microbial contamination is the use of preservatives. We review some frequently used preservatives, and we describe the mechanisms by which microorganisms develop resistance to these preservatives. Finally, because preservatives are inherently toxic, we review the efforts of researchers to utilize water activity and other non-preservative approaches to combat microbial contamination.
