THE INFLUENCE OF SUSTAINED RELEASE COATING PLASTICIZER ON THE RELEASE PROFILE OF A SOLUBLE DRUG FROM PELLETS

THE INFLUENCE OF SUSTAINED RELEASE COATING PLASTICIZER ON THE RELEASE PROFILE OF A SOLUBLE DRUG FROM PELLETS

Abstract

  The effect of plasticizers in insoluble sustained release film coating on the in vitro dissolution release of 1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl] cyclohexanol hydrochloride from multiparticulate delivery systems (e.g. in tablets, capsules etc.) was studied. The findings are equally applicable to coatings on monolithic tablets.

In preferred examples an external coating film, mainly comprised of insoluble polymers (e.g. ethylcellulose, acrylic polymers) and plasticizers, are sprayed on coated sugar spheres using Wurster equipment. These spheres are comprised of an internal coat or layer, which comprises 1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl] cyclohexanol hydrochloride and an optional intermediate protective coat.
Bilayer spheres were prepared in two coating steps using Wurster equipment.
 Firstly, sugar spheres NF (preferably 250 –1200mm) are coated with the internal coat, mainly comprised of between about 10 and about 300mg of 1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl] cyclohexanol hydrochloride (preferably 42.5-169.7 mg, equivalent to 37.5 – 150 mg of 1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl] cyclohexanol), with or without additional ingredients (polymers, such as ethylcellulose or anti tacking agents or binders) in alcoholic/aqueous/ hydroalcoholic vehicle.
Secondly, the optional intermediate protective coat comprised of  about 1 to about 10% w/w of the spheres (preferably 3-6 %), of a polymer, such as povidone, is applied.
This optional protective layer has several functions such as moisture barrier and prevention the abrasion of the raw material coating during successive processes.

Several formulations of the sustained release external film coat were studied.
The formulations are comprised of from about 55 to about 90% w/w (of solids remaining on the spheres) of insoluble polymer, together with a mixture of from about 10 to about 30% w/w of a lipophilic plasticizer such as dibutyl s...