Mini-Review Theme: Stability of Pharmaceutical Excipients Guest Editors: S.Narasimha Murthy and Michael A. Repka Microbial Stability of Pharmaceutical and Cosmetic Products Huy Dao, 1 Prit Lakhani, 1 Anitha Police, 1 Venkataraman Kallakunta, 1 Sankar Srinivas Ajjarapu, 1 Kai-Wei Wu, 1 Pranav Ponkshe, 1 Michael A. Repka, 1 and S. Narasimha Murthy 1,2,3 Received 25 April 2017; accepted 5 September 2017 Abstract. 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 contami- nated, 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. KEYWORDS: Microbial contamination; Pharmaceutical products; Stability; Cosmetics; Water activity; Preservatives. INTRODUCTION The microbial count in any pharmaceutical or cosmetic product can significantly affect its quality through the process of manufacturing the product or during its exposure to the environment in day-to-day use. The final product may contain microflora introduced from one or more sources, such as the raw materials (1), the processing equipment, the environment (2), the water used for the manufacture, and the manufactur- ing personnel (3). The microbial instability of pharmaceutical and cosmetic products is a crucial parameter in evaluating product quality and performance. Such instability may lead to alteration of the physicochemical properties of the product, which in turn may affect the shelf-life of the product or may become life threatening in certain cases (4). Microbial instability affects both sterile and nonsterile dosage forms. A wide range of preservatives and combinations of preservatives are used to counter microbial instability in pharmaceutical and cosmetic products. It has been reported that microbes have developed resistance to these preserva- tives in some cases (5). One of the novel and alternate approaches for minimizing microbial instability of a product is by controlling the water activity of the product. In this review, we summarize all the aspects related to the stability of the products, from the sources of contamination, to the process- ing condition, the prevention methods, how the microorgan- ism can develop resistance to preservatives, and new approaches to this matter. MICROFLORA IN PHARMACEUTICALS There are more than 22,000 species in the microorganism kingdom, with a variety of ways to classify them. Investigating their distribution in certain environments, ranging from production sites (e.g., clean room areas) to the market and post-market (FDA recall data), and finally to the patient (e.g., hospital environment) (6,7). Microorganisms in Manufacturing Sites Microorganisms in Clean Rooms Sandle reviewed more than 9000 samples over a period of nine years, and he develops a general picture about various microorganisms present in clean rooms. Although the Huy Dao, Prit Lakhani, Anitha Police, Venkataraman Kallakunta, Sankar Srinivas Ajjarapu, Kai-Wei Wu, Pranav Ponkshe, Michael A. Repka and S. Narasimha Murthy contributed equally to this work. 1 Department of Pharmaceutics and Drug Delivery, University of Mississippi School of Pharmacy, University, MS 38677, USA. 2 Institute for Drug Delivery and Biomedical Research, Bangalore, Karnataka, India. 3 To whom correspondence should be addressed. (e-mail: murthy@olemiss.edu) AAPS PharmSciTech ( # 2017) DOI: 10.1208/s12249-017-0875-1 1530-9932/17/0000-0001/0 # 2017 American Association of Pharmaceutical Scientists