Design, optimization, and characterization of Zolmitriptan loaded liposomal gels for intranasal delivery for acute migraine therapy

Abstract

Zolmitriptan is the primary drug for the treatment of Migraine. However, the bioavailability of the drug is low and requires repetitive administration leading to side effects. Zolmitriptan's bioavailability can be improved by incorporating it into liposomes as a topical intranasal gel. The formulation was developed using a Central composite design employing a response surface approach. The new formulations were tested for particle size, shape, drug entrapment efficiency, and in vitro drug release. Permeation experiments and histopathology in rats were also conducted to determine the formulation's safety. The vesicle size was found to be in the range of 103.82 ± 7.16 to 694.38 ± 1.02 nm, zeta potential –19.28 to -32.8 mV, Entrapment Efficiency from 55.49 ± 1.37 to 99.12 ± 0.36 %, and cumulative drug release from 59.71 ± 6.94 to 99.38 ± 0.13 % respectively. In-vitro drug release of G1 and G3 gel formulations showed a non-Fickian released pattern during the studies. A comparison of the permeation coefficient of G1 (0.539 μg/cm2) and G3 (5.3 μg/cm2) showed a slight variation in the drug release rate after 24 h. For the liposomal gel and its solution, we found a significant difference in drug penetration of p0.05 after 12 h compared to the control gel. There were substantial differences in bioavailability and pharmacokinetics between the optimal Liposomal Gel Formulation and other formulations, including the drug solution, liposomal suspension, and optimized formulation F12. The liposomal gel is non-irritating and safe for topical administration by histopathological investigations. Therefore, the study demonstrated that Zolmitriptan Liposomal gel has better efficacy, good tolerability, and enhanced bioavailability, making it an optimal treatment for acute Migraine.

Keywords

Zolmitriptan / Cholesterol / Liposomal gel / Central composite design / Soya lecithin / Pharmacokinetics / Skin permeation / Micelles formation

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