Defining design space for optimization of escitalopram ultra-fast melting tablet using suspension spray-coating technique: In-vitro and in-vivo evaluation

Abstract

In the pharmaceutical industry, the systematic optimization of formulation using Quality by Design (QbD) approach is economic, highly precise and ensures product quality. The current endeavor was aimed to prepare escitalopram ultra-fast melting tablets (UFMTs) based on QbD approach using suspension spray-coating technique. The (32) full factorial design was applied to obtain the optimal formulation in terms of; mannitol level (X1) and partially pre-gelatinized starch level (PPGS; X2) as independent formulation variables. The D-mannitol in certain formulations was spray-coated with a suspension of PPGS and granulated with distilled water (without PPGS) in other formulations using a fluid-bed granulator, producing granules compressed into tablets. The prepared tablets were tested for their mechanical strength, in-vitro and in-vivo disintegration, drug dissolution and in-vivo pharmacokinetic analysis using New Zealand rabbits. Results showed that the prepared tablets were tolerated with the USP criteria. Besides, ANOVA analysis demonstrated that X1 and X2 had a significant effect (P ≤ 0.05) on the dependent responses. Further, the developed tablets showed a good in-vitro/in-vivo correlation (R2 = 0.9953) in the disintegration time. Moreover, analysis of pharmacokinetic parameters suggested that optimized escitalopram UFMTs might have pharmaceutical bioequivalence to the marketed product. Finally, QbD considered an efficient paradigm for product optimization.