QUALITY BY DESIGN-DRIVEN FORMULATION DEVELOPMENT AND OPTIMIZATION OF ENALAPRIL MALEATE LOADED MUCOADHESIVE MICROSPHERES: IN VITRO AND IN VIVO CHARACTERIZATION

SOMESHWAR KOMATI; MUDDANA ESWARA BHANOJI RAO; SURYAKANTA SWAIN; DEBASHISH GHOSE

doi:10.22159/ijap.2023v15i4.47905

Authors

SOMESHWAR KOMATI PhD research scholar Pharmacy, Biju Patnaik University of Technology, Rourkela, Odisha and Department of Pharmaceutics, University College of Pharmaceutical Sciences, Palamuru University, Mahaboobnagar, Telangana-509001, India
MUDDANA ESWARA BHANOJI RAO Department of Pharmaceutics, Calcutta Institute of Pharmaceutical Technology and AHS, Banitabla, Uluberia, Howrah-711316, West Bengal, India
SURYAKANTA SWAIN School of Pharmacy and Paramedical Sciences, K. K. University, Nalanda-803115, Bihar, India https://orcid.org/0000-0002-1485-343X
DEBASHISH GHOSE Department of Pharmaceutics, Roland Institute of Pharmaceutical Sciences, Khodasinghi, Berhampur-760010, Ganjam, Odisha, India https://orcid.org/0000-0001-9845-2758

DOI:

https://doi.org/10.22159/ijap.2023v15i4.47905

Keywords:

Mucoadhesion, Ionic gelation, Central composite design, Loose surface crystal study, In vitro drug release, Pharmacokinetics parameters, Stability studies

Abstract

Objective: The study is to formulate the enalapril maleate-loaded mucoadhesive microspheres with varied compositions of selected polymers for developing the oral controlled release formulations prepared by ionic gelation method and optimization through central composite design.

Methods: Systematic optimization of microspheres was accomplished by the central composite design and characterized for particle size, entrapment efficiency, in vitro drug release and ex vivo mucoadhesion strength, which indicated that microspheres were a consequence to be spherical and free-flowing in nature. The microspheres exhibited high drug entrapment efficiency and in vitro drug release in a sustained manner, which was considered to be dependent on the concentration of rate-controlling polymers. The microspheres are showed 389.2 to 850 µm particle size and 22.36 to 85.22 % encapsulation efficiency. In vitro studies indicated optimized formulation showed 89.26% drug release after 12h and reduced blood pressure effectively.

Results: The pharmacokinetic parameters were evaluated with C_max of 75.39 µg/ml, t_max of 8h, and AUC of 53.55 µg/hr/ml, elimination rate constant of 0.0392 and t_1/2of 10h. The stability studies were conducted for 3 mo under various conditions and identified no significant deviations in selected key quality attributes.

Conclusion: The formulated mucoadhesive microspheres of enalapril maleate tend to reduce the blood pressure in the animal model, with the novel drug delivery approach in the efficient management of hypertension.

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