Realizing Process Analytical Technology (PAT) in Process Development by Implementation of Near-Infrared (NIR) Spectroscopy
by Michael Fowler, Janssen Vanderhooft, and Venkatesh Subramanyan
Article published in Pharmaceutical Engineering Magazine, September/October 2013
Topical Gel Background
One critical activity common to most transdermal products is the development and optimization of mix processes for semi-solid, liquid solutions, gels, emulsions, and suspensions. Some Critical Quality Attributes (CQAs) for transdermal products at the mix stage are assay, content uniformity, viscosity, specific gravity, solvent content, and pH. Each of these CQAs has the potential to be monitored by PAT. Although NIR spectroscopy is capable of measuring many quality attributes, only content uniformity and viscosity were characterized in the study discussed in this study. To simplify the discussion of the mix process, any activity related to mixing, blending, homogenizing, or similar will simply be referred to as mixing. Mix processes for topical gel emulsions and suspensions can be particularly challenging to develop.7 Determining mix end points by visual examination is virtually impossible be cause products are often opaque; therefore, samples must be collected at discrete intervals for testing CQAs. In addition, the resources required to test these in-process samples make this approach less desirable. There are often mix stages between individual ingredient additions, further increasing the number of experiments that must be conducted to determine mix end points. PAT instrumentation allows these experiments to be conducted continuously, providing real-time feedback during the development mix process. The topical gel formulation for this study was comprised of typical components with common pharmaceutical functions, including solvents, Active Pharmaceutical Ingredients (APis), preservatives, gelling agents, emulsifiers, and enhancers. A Bruker Optics, Inc. NIR Matrix-F spectrometer and probe was used for this study. A Charles Ross & Son Company 15 gallon stainless steel multiple-shaft mixer was used for gel mixing.
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