Scientific Publications by FDA Staff

Int J Pharm 2020 Aug 30;586:119495

Factors affecting the particle size distribution and rheology of brinzolamide ophthalmic suspensions.

Vo A, Feng X, Patel D, Mohammad A, Kozak D, Choi S, Ashraf M, Xu X

The performance of topical ophthalmic suspensions, namely the drug release characteristics and ocular retention in addition to its physical stability depends on the drug particle size distribution (PSD) and the viscosity of the suspension. An in-depth knowledge of the effects of formulation and manufacturing process on these critical quality attributes may facilitate the product and process development, quality control, and support regulatory policy and approval. The current study has investigated the effect of formulation and process parameters on the quality attributes of brinzolamide ophthalmic suspensions. In the first step, three milling techniques (probe sonication, microfluidization, and media milling with a planetary centrifugal mixer) were evaluated for manufacturing brinzolamide suspension. Out of the three techniques, the centrifugal planetary mill yielded the narrowest PSD and thus was considered the most viable lab-scale technique for this purpose. In the next step, various process parameters of media milling were evaluated using a central-composite experimental design. The independent variables included bead size, agitating intensity, and process time while the PSD of drug particles (D(50)) was the response variable. The effect of shear rate and shear time of the homogenization process and the concentration of carbomer on the rheological properties of the suspension were studied using a Box-Behnken design. Additionally, effects of sodium chloride and mannitol concentration on the rheological properties of the suspension was also investigated. Sodium chloride was found to exert a pronounced effect on rheology of the suspension. Despite variations in the carbomer concentration, a suspension of comparable rheology could be prepared by controlling the process parameters namely the shear rate and process time.