Abstract

FORMULATION AND EVALUATION OF SUPPOSITORY INCORPORATED WITH ANTIHYPERTENSIVE DRUG LOADED MICROSPHERES

Mubashira N. P.*, Geetha V. S., Jumana K. K. and Farsana T.

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Abstract

The aim of the present study was to prepare a sustained release suppository of Diltiazem HCl, an antihypertensive drug for rectal administration. Firstly, the microspheres of Diltiazem hydrochloride were formulated using ethyl cellulose by non-aqueous solvent evaporation technique. The microspheres were optimized by using design expert software trial version 13 by central composite statistical design with 2 factors (drug polymer ratio and rotations per minutes), 2 levels and 13 Runs. The results indicated that the concentration of polymer have significant effects in entrapment efficiency and drug release, while the stirring rate have minimal effects. The drug release rate decreased at higher polymer concentration due to increase in the diffusional path length. The results demonstrated a good relationship between the predicted and experimental values, confirming the validity of the model. The optimized microspheres were evaluated for percentage yield, particle size, entrapment efficiency, scanning electron microscopy and in vitro drug release studies. The prepared microspheres exhibited prolonged drug release up to 12 hr in phosphate buffer pH 7.2. Sustained release suppositories using PEG 6000 and cocoa butter as bases were formulated with incorporation of microspheres by fusion method. The formulated suppositories was evaluated for its physical parameters, melting point studies, liquefaction time, drug content and in vitro drug release. The results suggested that all the formulations were physically stable complying with the official specifications. Conventional suppositories without microspheres released the drug within 2 h compared to the sustained release suppositories releasing the drug till 12 h from the dispersed microspheres. The drug release from cocoa butter suppository was slow as compared to the PEG suppository. The cocoa butter suppository based suppository released only 61.4 % drug after 12 hrs, but the PEG suppository released 88.3% drug after 12 hrs. Hence the PEG suppository is better for incorporation of microspheres. The suppository formulations showed peppas model with non-fickian drug release mechanism. The results of investigation clearly suggest that a rectal drug delivery system of Diltiazem hydrochloride can be successfully designed to achieve a sustained delivery of drug for particular clinical conditions.

Keywords: Microspheres, DiltiazemHCl, Suppository, Hypertension.