Abstract

Background: Hypertension is the most common cardiovascular disease worldwide and number one cause of death. Its related morbidities also impose huge economic burdens on population. The aim of the present investigation was to prepare thermal gel of Diltiazem Hydrochloride (DTZ) with different ratios of Poloxamer 407 (PLM 407) and Hydroxypropyl methylcellulose K100M (HPMC K100M) and to characterize their in vitro parameters, ex vivo permeation and in vivo antihypertensive activity.

Methods: Cold method was used to prepare thermal gel of DTZ. In vitro testing such as interaction study using FTIR and DSC method, bioadhesive strength was measured using modified balance method, in vitro release study performed using dialysis bag method. Ex vivo permeation study was carried out by using a cylindrical glass diffusion cell. Rabbit model was used to perform in vivo antihypertensive activity.

Results: The FT-IR spectra and DSC thermograms demonstrated the absence of interaction between DTZ and selected polymers. Based on the results obtained from in vitro studies, formulation DT3 having 1% w/w of HPMC K100M and 25% w/w of PLM 407 was selected as optimized thermal gel. Among the permeation enhancers (PEs) used in this study (such as L-menthol, transcutol and isopropyl myristate (IPM) at 10% (w/w)) L-menthol present in gel formulation DTm showed highest flux of 355.234 μg/cm2/h across abdominal skin of rat. Rabbit group treated with DTm exhibited prolonged (up to 8 h) antihypertensive effect in normotensive rabbits compared to orally treated group.

Conclusion: The optimized gel with L-menthol has a promising potential as an effective product in the treatment of hypertension and expected to provide a better alternative to oral DTZ formulations with improved patient compliance.

Keywords: Anti-hypertensive activity, diffusion, flux, permeation enhancers, stratum corneum, thermal gel.