Formulation and Characterization of Cinnarizine Targeted Aural Transfersomal Gel for Vertigo Treatment: A Pharmacokinetic Study on Rabbits.

INTRODUCTION AND AIM: Cinnarizine is indicated orally for treating vertigo associated with Ménière's syndrome and has a local anesthetic effect as well. The present study aims to develop an aural Cinnarizine mucoadhesive transfersomal gel to overcome the first-pass metabolism. METHODS: Eighteen Cinnarizine transfersomes were prepared by the thin-film hydration technique using different types of phosphatidylcholine and edge activators in different ratios. Formulae were tested for their appearance, entrapment efficiency, and in-vitro drug release after eight hours. F1, F4, F7, F9, F10, and F12 were selected to be examined for particle size, polydispersity index, and zeta potential. According to the previous parameters, F1 and F10 were incorporated into gels using different polymers according to factorial design 23. The eight gels were tested for appearance, pH, mucoadhesion, spreadability, drug content, in-vitro drug release after eight hours, and rheology. The transfersomal gel F1A was subjected to FTIR analysis and in-vivo pharmacokinetic study. RESULTS: The transfersomal dispersion colors were ranging between the white and yellow. Their EE % ranged from 64.36±1.985% to 94.09±1.74%, and their in-vitro release percentages were between 61.82±1.92% and 95.92±1.18%. Also, the vesicles PS ranged from 212.3±30.05nm to 2150±35.35nm, DI from 0.238±0.134 to 1±0.00 and zeta potential from -57.5±2.54 to +4.73±1.57 mV. The transfersomal gels showed pseudoplastic behavior, pH range of 5.5 to 8, a mucoadhesive force of 169.188±1.26 to 321.212±6.94 (dyne/cm2×102), spreadability of 40 ±7.03mm to 138 ±3.77mm, and in-vitro drug release of 81.63±1.128% to 97.78±0.102%. The IR spectra of the (drug-excipients) physical mixture revealed that there were no shifts of incompatibility. The in-vivo pharmacokinetic study illustrated that [AUC]0-24 of F1A was significantly higher than that of tablets at (P< 0.05), equivalent to 703.563±26.470 and 494.256±9.621ɲg.hr/mL respectively. CONCLUSION: The study revealed that Cinnarizine aural mucoadhesive targeted delivery provides an improved systemic bioavailability over the conventional oral route.

Non-ionic surfactant based vesicular drug delivery system for topical delivery of caffeine for treatment of cellulite: design, formulation, characterization, histological anti-cellulite activity, and pharmacokinetic evaluation.

Cellulite is a common topographical alteration where skin acquires an orange peel or mattress appearance with alterations in adipose tissue and microcirculation. This work aims to develop and evaluate a topical niosomal gel formulae with good permeation to reach the subcutaneous fat layer. Several caffeine niosomal dispersions were prepared and incorporated into gel formulae using Carbopol 940 polymer, chemical penetration enhancers, and iontophoresis, then the prepared gels were applied onto the skin of rats and anticellulite activity of caffeine from the prepared gels compared to that of the commercial product Cellu Destock® was evaluated by histological study of the skin and measurement of plasma level of caffeine passing through the skin using liquid chromatography (LC/MS-MS). Results of histology revealed reduction of size and thickness of fatty layer of rat skin in the following order: FVII > FXIV > Cellu Destock® > FVII + Iontophoresis > FXIV + Iontophoresis. Pharmacokinetic results of caffeine in plasma revealed that Cmax, Tmax, and AUC0-12h decreased in the following order: FXIV > FVII > Cellu Destock®. These results conclude that incorporation of caffeine niosomal dispersion into gel matrix with penetration enhancers and iontophoresis resulted in improvement in penetration of caffeine through the skin into the underlying fatty layer in treatment of cellulite.