Calcium Ion-Sodium Alginate-Piperine-Based Microspheres: Evidence of Enhanced Encapsulation Efficiency, Bio-Adhesion, Controlled Delivery, and Oral Bioavailability of Isoniazid.

Abstract

Isoniazid (INH) is a first-line chemotherapeutic drug employed in the management of tuberculosis. However, its extensive first-pass metabolism, short-life life, and low oral bioavailability confined its medical application. Therefore, the calcium ion-alginate-piperine microspheres (INH-CaSP Ms) was prepared to enhance encapsulation efficiency, controlled delivery, and oral bioavailability of INH. The INH-CaSP Ms was developed using a modified emulsification method and optimized via Box-Behnken design (BBD). Optimized INH-CaSP Ms were characterized for encapsulation efficiency, differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), bio-adhesion, in vitro dissolution, ex vivo permeation, and oral bioavailability studies. Characterization studies confirmed the formation of microspheres. The INH-CaSP Ms showed spherical microspheres with enhanced encapsulation efficiency (~ 93.03 ± 1.54% w/w). The optimized INH-CaSP Ms exhibited higher bio-adhesion around (~ 81.41 ± 1.31%). The INH-CaSP Ms enhanced the dissolution rate of INH (~ 57%) compared to pure INH (~ 57%) and INH-SA Ms (~ 81%) in simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.4). The same formulations improved the permeation rate of INH (~ 90%) compared to pure INH (~ 55%) and INH-SA Ms (~ 80%). The oral bioavailability results indicated that INH-CaSP Ms appreciably improved the oral bioavailability of INH via increasing the Cmax, Tmax, t1/2, and AUC parameters compared to pure INH. The study demonstrates that the development of INH-CaSP Ms via cross-linked coordinate bond interaction between divalent cation calcium ion-alginate complex and anion piperine bio-enhancer is an effective approach for enhancing the encapsulation efficiency, bio-adhesion, controlled release, and oral bioavailability of INH.