Quality by Design Enabled β-Cyclodextrin Complexes of Lisinopril by Kneading Method: Improved Solubility and Bioavailability

Abstract

Background: The primary intent of the study is to formulate the inclusion complex of lisinopril with the varied compositions of polymers like β-cyclodextrin for the enhancement of oral drug solubility and bioavailability using QbD approach. Methods: The application of Box-behnken design to determine the optimized run from the prepared inclusion complexes. The physical kneading technique with β-cyclodextrin at varied amounts was used to create the inclusion complex of lisinopril. Results: The FT-IR analysis study confirmed the selected drug, polymers, and other excipients showed no physical interactions. The prepared inclusion complexes' particle sizes and encapsulation efficiency were between 802 to 3259μm, 19.22 to 93.28%. The optimized formulation batch (F5) showed 90.16% in vitro drug release at 24h compared to the pure drug. From the in vivo study, the pharmacokinetic parameters for the optimized formulation (F5) were found to be Cmax of 94.336 ng/ml, Tmax of 12h, and AUC 94.336 ng.h/ml, Kel of 0.0395h-1 and t1/2 of 12h. After three months, stability studies for the optimized formulation batch indicate no change in drug entrapment efficiency and other parameters. Conclusion: The β-cyclodextrin inclusion complex of lisinopril exhibited a 2-fold increase in the oral bioavailability of the model drug, which will be the novel drug-delivery strategy for the treatment of hypertension.