Background: Nimodipine (NM), is a dihydropyridine calcium channel blocker with poor oral bioavailability (BA) of about 13% due to first-pass metabolism and P-gp efflux. Objective: The present work aimed to study the influence of the charge inducer and its combination with P-gp inhibitor to improve the oral bioavailability of NM by developing a suitable delivery system of Submicron Lipid Emulsion (SME). Methods: Five SME formulations of NM were prepared by homogenization followed by ultrasonication. Prepared SMEs were characterized for particle size, PDI, Zeta Potential (ZP), Entrapment Efficiency (EE), and drug content. In vitro, release studies were performed in 0.1N HCl and pH 6.8 phosphate buffer by open tube method. The physical stability of all NM–SMEs was tested by the individual effects of centrifugation, dilution (desorption stress), and storage. Bioavailability studies were conducted on male Wistar rats after oral administration of NM suspension and F1 to F5 SME formulations. Results and conclusion: Five NM- SMEs were developed with a mean size ranging from 93 - 137 nm, Zeta potential of – 26 ± 1 mV (negatively charged), +45.8 to +46.3 mV (positively charged), and PDI of 0.15 - 0.25. The in vitro release studies showed that relatively more cumulative percentage release of NM – SMEs in 0.1N HCl than in pH phosphate buffer during 24 hours. The physical stability of NM–SMEs indicated that they were stable to the effects of centrifugation, dilution, and storage. Pharmacokinetic (PK) studies showed that the oral bioavailability of NM in F4 SME was significantly higher than that of all other formulations. Taken together, the results indicated the development of a stable lipid-based carrier, F4 SME to improve the oral bioavailability of this drug by minimizing first-pass metabolism due to lymphatic transport, reducing the efflux by P-gp inhibition, and further, by increased uptake of the positively charged F4 SME globules by enterocytes. Future: The research study findings increase the possibility of developing NM F4 SME by the pharmaceutical industry for the patient’s benefit.
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