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In Vitro Techniques Equipped to Study Clinically Relevant Controlled Release Products

Young PM, Traini D, Salama RO.

RDD Europe 2011. Volume 1, 2011: 79-88.

Abstract:

It is important to understand the fate of particles following deposition in the respiratory tract. Local bioavailability in the lung is influenced by drug solubility, lipophilicity, chemical structure and size. A range of in vitro ‘glass’ and in vitro cell models exist that may have the capability of predicting in vivo behavior. This study evaluates the ability of USP Apparatus 2, modified USP Apparatus 4, and a Franz Diffusion cell method to differentiate the release profiles of a series of co-spray dried polymers containing disodium cromoglycate. The drug release of two of these formulations was also investigated using an in vivo ovine model. Our findings suggest that conventional pharmacopeial dissolution methods (i.e., USP Apparatus 2) were insensitive to the release profiles of sodium cromoglycate from microparticles containing polyvinyl alcohol (PVA), at concentrations ranging from 0-90% w/w. In comparison, the Franz diffusion cell showed significant differences in release profiles. In vivo studies showed prolonged drug plasma concentrations and increased bioavailability of disodium cromoglycate from microparticles containing PVA. The importance of choosing appropriate in vitro methodology to study the fate of drug molecules cannot be understated; however, defining a suitable protocol, that is applicable to the wide range of drug molecules and formulation approaches used, can be a challenge.