Formulation, evaluation, and pharmacokinetics of isradipine proliposomes for oral delivery

Proliposomes loaded with isradipine were prepared successfully to enhance the oral bioavailability of isradipine. In this study, proliposomes were prepared by film deposition by the carrier method with varying ratios of hydrogenated soy phosphatidyl choline (HSPC) and cholesterol using spray-dried mannitol (Pearlitol SD 200) as the carrier. The formulation containing an equimolar ratio of HSPC and cholesterol showed smaller vesicle size, high surface charge, and entrapment efficiency. The formation of liposomes and surface morphology of optimized proliposome formulation was studied by optical and scanning electron microscopy, respectively. Fourier transform infrared, differential scanning calorimetry, and powder X-ray diffractometry studies were performed to assess the solid-state characteristics of the formulation. Ex vivo permeation enhancement assessed from flux, permeability coefficient, and enhancement ratio were significantly higher for proliposomes, compared to control. The pharmacokinetic parameters were evaluated in male albino Wistar rats, and a significant improvement in bioavailability (2.4-fold) was observed from the optimized proliposome formulation, compared to control (oral suspension). The stability study revealed that the formulations are stable when stored at 4°C.