Stabilized Pharmaceutical Formulation
Publication Date: 2002-Sep-17
The IP.com Prior Art Database
Stabilized Pharmaceutical Formulation of an Acid Labile Benzimidazole Compound and Its Preparation
Substituted benzimidazoles are substituted sulfoxides, which are potent inhibitors of gastric acid secretion. These compounds are susceptible to degradatio n and/or transformation in acidic media. In order to provide a pharmaceutical composition containing such acid labile substances, which is not degraded in the gastrointestinal tract, the dosage may be enteric coated. However, pharmaceutically acceptable enteric coating materials often contain acidic reacting groups. Therefore, directly covering the acid susceptible drug with these enteric coating materials may cause the degradation of the acid labile substance. A large number of publications and patent applications are available, describing enteric -coated pharmaceutical formulations of acid labile benzimidazoles, where the cores contain the acid labile compounds mixed with alkaline reacting substances. Some of the publications teach about additional separating layers, which rapidly disintegrate in gastric fluid. Our work herein disclosed relates to a stabilized pharmaceutical composition in the form of a multi-particulate delivery system composed of an inert (e.g. sugar) core coated with: a drug layer compris ing a non-alkaline reacting substance; a binder and a benzimidazole derivative drug; an intermediate coating comprising alkaline reacting agents and a binder; and an outer enteric layer.
A first layer is applied to an inert (e.g. sugar, spherical) core. Th is layer contains a mixture of the benzimidazole compound as an active ingredient, a binder consisting of an inert polymer, such as HPMC, HPC, PVA, PVP, and an anti-tackiness agent, such as talc (or silicon dioxide or magnesium stearate). A second isolatio n layer consists of an inert polymer binder, such as HPMC, HPC, PVA, PVP together with an alkaline reacting agent, such as basic inorganic salts (e.g. magnesium carbonate, magnesium oxide, sodium hydroxide), or organic bases (TRIS, meglumine). A third layer comprised of an enteric coating is then applied. The coating process is performed in three discrete steps using a fluidized bed equipped with Wurster column apparatus (Bottom spray technique).
Firstly, the sugar spheres (preferably 250-1200 micron) are coated with an aqueous suspension comprising 4-16% (w/w of drug layered core) of a benzimidazole derivative, 2-16% (w/w of drug layered core) of a binder polymer, preferably, HPMC, HPC, PVA, PVP and 2-16% (w/w of drug layered core) of antitackiness agent, preferably talc or magnesium stearate.
Secondly, the intermediate layer comprising an inert polymer, preferably 20-60% (w/w of intermediate layer) HPMC, HPC, PVA, PVP and 40-80% (w/w of intermediate layer) of stabilizing agent, such as magnesium carbonate, magnesium oxide, sodium hydroxide or organic bases such as TRIS, meglumine, are sprayed from aqueous or hydro-alcoholic suspension. The adequate layer thickness is a...