Pharmaceutical Technology - May 2018

Pharmaceutical Technology eBook - Biologics and Sterile Drug Manufacturing

Issue link:

Contents of this Issue


Page 30 of 61

Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING 2018 31 the potential for degradation by hydrolysis and, therefore, improves the product's shelf life. Residual moisture content is a CQA of lyophilized finished products. According to the International Council for Harmonization (ICH) Q6A guidance, the water content of a finished product should have a test pro- cedure and a specification when appropriate (1). It is commonly assumed that removing as much water as possible from the finished product is cru- cial; however, over-drying a finished product, or removing too much water, can have detrimental effects, such as altering a crystalline hydrate or inducing protein unfolding (2). Therefore, under- standing the role water plays and how the water interacts with the finished product is important. There are two ways water can be present and inter- act with finished products: adsorbed and absorbed water (3). Adsorbed water is on the surface of the product, and absorbed water resides in the bulk of the finished product (3). Water interacts differently with amorphous and crystalline structures. Crystalline structures gen- erally do not have as high an affinity to absorb water as amorphous structures because of the high degree of order, tight crystal packing, and rigid structure. Amorphous structures are not highly ordered or rigid, allowing the structure to more readily sorb water. Water also acts as a plasticizer and will affect the dried product glass transition temperature: As the residual moisture content in- creases, the glass transition temperature decreases. Lowering the glass transition temperature can cause long-term stability issues, sometimes allow- ing the amorphous material to crystallize. When material crystallizes, water will be released. This freed water can then affect the API and cause hy- drolysis reactions to occur, further degrading the finished product. The effects of water on a finished product can lead to a number of other changes in- cluding chemical or biochemical degradation and can alter reconstitution behavior or promote col- lapse of an open, porous structure. Because water can be present in a lyophilized product in a number of ways, measurement of the residual moisture and the method used to measure the water content must be accurate, precise, and, preferably, discriminating. The residual moisture content of a lyophilized product can be quantified by using a number of different methods. It is im- perative the method used to quantify the residual moisture is appropriate for the finished product being tested, the quantity of water, and the type of water present (adsorbed or absorbed). Sample preparation considerations The majority of lyophilized products are amor- phous, have a significantly large surface area, and a propensity to sorb moisture when exposed to the atmosphere. Therefore, the most important aspect in all residual moisture testing methods is prevent- ing moisture uptake during sample preparation and handling. Care should be taken to minimize the exposure of the product to atmospheric moisture and the potential risk of skewing the test results. Lyophilized products are sometimes stoppered at reduced headspace pressure. During sample preparation, the product and its container must be reverted to atmospheric pressure. If this is not performed prior to testing and the test method re- quires weighing of the sample pre- and post-testing, the initial pre-testing weight will be incorrect. The sample can be brought to atmospheric pressure by introducing dry air or nitrogen piercing the stop- per with a needle; or, the stopper can be removed

Articles in this issue

Archives of this issue

view archives of Pharmaceutical Technology - May 2018 - Pharmaceutical Technology eBook - Biologics and Sterile Drug Manufacturing