In vitro physicochemical characterization and dissolution of brinzolamide ophthalmic suspensions with similar composition.

Anh Vo, Xin Feng, Deval Patel, Adil Mohammad, Mehulkumar Patel, Jiwen Zheng, Darby Kozak, Stephanie Choi, Muhammad Ashraf, Xiaoming Xu

International journal of pharmaceutics 2020 Oct 15

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The quality of an ophthalmic suspension is crucial for its in vivo performance, and often impact product's effectiveness. An in-depth understanding of critical quality attributes (CQAs) of ophthalmic suspensions such as particle size distribution (PSD) and rheology, as well as the impact of these CQAs on product performance are important for successful product development, quality control, and regulatory approval. This study employed brinzolamide ophthalmic suspension, 1%, as a model ophthalmic product, and six batches were manufactured using an innovative planetary centrifugal milling (PCM) process. Three batches were manufactured to have distinctly different PSD. These three batches had qualitatively (Q1) and quantitatively (Q2) the same composition as the model drug product (i.e., Azopt), while the differences in PSD were introduced by changing only the manufacturing process parameters. On the other hand, changes in rheology were introduced by altering the input level of the viscosity enhancing polymer in the formulation. A systematic approach was employed to understand the relation between manufacturing process parameters, CQAs, and in vitro product performance. Among the evaluated CQAs, PSD, rheology, surface tension, and drug dissolution were found more sensitive to the changes in the manufacturing processes. Most notably, we developed a rapid dissolution method (completed within minutes) employing in-situ fiber optic UV dissolution system. This novel dissolution method mimics the environmental conditions of the eye such as dissolution under "non-sink" condition and under high shear (from blinking). The method was highly discriminatory to differences in the PSD in the suspension. This study also revealed an important relation between the PSD of the suspension and its rheology which originated as a result of an interaction at the molecular level between the solid drug particles and the viscosity enhancing polymers. These findings underscore the need to evaluate CQAs of the ophthalmic suspensions in concert rather than separately when comparing ophthalmic drug products and product performance. Published by Elsevier B.V.

Citation

Anh Vo, Xin Feng, Deval Patel, Adil Mohammad, Mehulkumar Patel, Jiwen Zheng, Darby Kozak, Stephanie Choi, Muhammad Ashraf, Xiaoming Xu. In vitro physicochemical characterization and dissolution of brinzolamide ophthalmic suspensions with similar composition. International journal of pharmaceutics. 2020 Oct 15;588:119761