Design and Evaluation of Osmotic Drug Delivery System of Efonidipine

Abstract

Introduction: The aim of the present research work was to design an elementary osmotic pump (EOP) of efonidipine
hydrochloride (EFH), a biopharmaceutical classification system class II drug. Materials and Methods: To enhance
the solubility of EFH by novel co-amorphous solid dispersion technique, drug-loaded solid dispersion composed
of efonidipine/co-former at a weight ratio of 1:1, 1:2, 1: 4, 1:8, and 1:12 was prepared by fusion method. Based
on the drug release profiles, efonidipine/pimelic acid dispersions were optimized. To formulate the core tablets,
sodium chloride and mannitol were used as osmotic agents. Four distinct core compositions, labeled as EF1
through EF4, were prepared following a 22 full factorial design approach to systematically optimize the drug’s
release profile, and four different coating compositions (a, b, c, and d) were applied to four distinct formulations
(EF1 to EF4) resulting in a total of 16 formulations. EOP tablets were prepared by applying a semipermeable
membrane, cellulose acetate with an orifice on the surface. Results and Discussion: Evaluation of the prepared
EOP tablets showed satisfactory results, with all 16 formulations exhibiting complete release of efonidipine
over approximately 24 h. The steepest ascent method was employed to determine the appropriate quantities, and
optimized formulation was designed to release the drug in a controlled manner over a 24-h period. The study
demonstrated that the main factor affecting drug release was osmosis alone, and factors such as agitation and
stagnant conditions had no significant impact on drug release. As a result, a successful controlled drug delivery
system for efonidipine over a 24-h duration was developed using an optimized technique based on a 24 factorial
design. In vivo study was performed in New Zealand white rabbits and various parameters such as Cmax, tmax,
AUC, AUMC, and MRT were calculated and compared with that of marketed tablet. Conclusion: In summary,
efonidipine osmotic pump tablets presented controlled release in vitro, high bioavailability in vivo and a good
in vitro-in vivo correlation.