Release characteristics of drug having different solubilities from matrix pellets containing glycerides

Abstract

The release properties of having different solubilities (propranolol hydrochloride and diclofenac sodium) from the glycerides matrix pellets were investigated. The pellets were prepared using extrusion and spheronization technique. Glyceryl monostearate, hydrogenated cottonseed oil (Lubritab®) and glyceryl behenate (Compritol®ATO 888) were used as matrix forming agents. Lactose and microcrystalline cellulose (Avicel®PH 101) were chosen as pellectization aids. The following factors that might influence the drug release were examined: amounts of glycerides, drug loadings, sizes of pellet, and pellets curing process. The glycerides pellets of propranolol hydrochloride could not provide the prolonged drug release except the formulation containing Compritol®ATO 888 that could maintain the release for eight hours. Due to its very low solubility in acidic medium, diclofenac sodium pellets exhibits lower than 3 percent release in 0.1 N HCI throughout the duration of twelve hours, while could give sustained action for twelve hours in phosphate buffer pH 6.8 with all glycerides employed. Smaller sizes of the pellets were found give the faster release of the drugs. The addition of polyethylene glycol 1450 (PEG 1450) and polysorbate 80 (Tween®80) into diclofenac sodium pellets did not exerted an increasing effect on drug release in acidic medium. Following the curing of propranolol hydrochloride matrix pellets in fluidized bed dryer, only Lubritab® containing pellets showed reduction of drug release compared with uncured pellets. It could be concluded that the glyceride pellets matrix might be suitable for low solubility drug substance. If more prolonged release action is required, the pellets should be compressed into the tablet matrices. As it was shown, the matrix tablets prepared by compression of the pellets provided the better-sustained release actions of both propranolol hydrochloride and diclofenac sodium.