LIPOID SPC-3-Based Coprecipitates for the Enhancement of Aqueous Solubility and Permeability of Ranolazine

Abstract

The study was aimed at exploring the feasibility of LIPOID SPC-3 as a coprecipitate carrier to enhance the aqueous solubility and permeability of ranolazine, a BCS class II drug. LIPOID SPC-3-based coprecipitates of ranolazine (RNZ-SPC-CP) were developed using the solvent method. The developed formulation was physico-chemically characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), powder x-ray diffractometry (PXRD), and drug content. Functional evaluation of RNZ-SPC-CP formulations was carried out by solubility analysis, in vitro dissolution studies, fed vs. fasted state dissolution comparison, and ex vivo permeation studies. The SEM studies revealed dissimilar morphological characteristics of pure ranolazine, LSPC-3, and RNZ-SPC-CP formulations. The physico-chemical analysis confirmed the formation of the coprecipitate. Optimized RNZ-SPC-CP1 demonstrated a noteworthy increase (~ 18-fold) in water solubility (~ 92.23 ± 1.02 μg/mL) over that of pure ranolazine (~ 4.94 ± 0.06 μg/mL) and physical mixture (PM) (~ 30.21 ± 2.12 μg/mL). Optimized RNZ-SPC-CP1 appreciably enhanced the rate and extent of ranolazine dissolution (~ 85%), compared with that of pure ranolazine (~ 21%) and PM (~ 35%). Similarly, the permeation rate of ranolazine from optimized RNZ-SPC-CP1 formulation was found to be enhanced significantly (~ 83%) over that of pure ranolazine (~ 19%) and PM (~ 32%). In the fed state, the RNZ-SPC-CP1 improved the rate and extent of ranolazine dissolution, compared with those of fasted state dissolution. The results conclude that RNZ-SPC-CP could be used as a promising approach for enhancing the aqueous solubility and permeation rate of ranolazine.