Assay In-vitro Dissolution Study and Hydrolytic Stability Study of Diltiazem Hydrochloride From Marketed GEL Formulations

Abstract

Diltiazem Hydrochloride is a calcium channel blocker – antihypertensive drug. Its novel dosage form available in the market is Diltiazem Hydrochloride gel used in the treatment of anal fissure. The aim of the present work was to develop and validate an accurate, simple, precise and cost effective UV Visible spectrophotometric method for its estimation in gel formulations. The efficacy of semi-solid dosage form depends on its drug release profile so it is essential to study the in – vitro drug release profile by Franz diffusion cell. In UV-Visible spectrophotometric method, estimation of Diltiazem Hydrochloride was done on its λmax 236nm using double distilled water as a solvent. The calibration curve was found to be linear in the range of 2.5- 25μg/ml for Diltiazem Hydrochloride (r2 =0.998). In-vitro drug release was performed by Franz diffusion cell and maximum % drug release was found to be 82.33% for DILZEM gel and 79.83% for DILTIACT gel at 120min time period. Assay was performed by RP-HPLC method with XTerra C18 column (150mm× 4.6mm ,5μm) with mobile phase containing Methanol:Acetonitrile:Ammonium acetate buffer (38:26:36 %v/v/v) at detection wavelength 249nm. The linearity of Diltiazem Hydrochloride was found to be 5-30μg/ml (r2=0.999). Assay of two marketed formulations was found to be 86.86% for DILZEM gel and 87.43% for DILTIACT gel. Less assay of gel formulations indicates the degradation of the drug so it was necessary to perform degradation study. The hydrolytic degradation study of Diltiazem Hydrochloride API and Gel formulations were carried out at different temperature, time and pH. 1.80% and 6.22% degradation for API was found in acidic and alkaline condition respectively.PDA spectra of both degradation product and DH API were same indicative that this degradation product is des-acetyl diltiazem.