Influence of pharmaceutical factors on the dissolution profile of granules for oral suspension with nimesulide

Abstract

In vitro dissolution profiles are investigated to predict the behavior of the drug in the body and to establish its effectiveness. The choice of medium and dissolution conditions depends on the class of BSC of the active substance or substances that are part of the drug. In this work, nimesulide was chosen as a model substance, which is a sparingly soluble substance of class II BSC, when bioavailability is limited only by dissolution. The aim of the work was to establish optimal conditions for determining the dissolution profiles of Nimesulide, granules for oral solution, 100 mg/2 g and to study the effect of compositional variables on the release of API. The subject of the study was granules for oral suspension, made on the basis of nimesulide. In the experiment used the substance nimesulide 3 manufacturers, corn starch and macrogol 20 (polyethylene glycol) cetostearyl ether. The particle size of the substances was investigated by laser diffraction. Determination of nimesulide release was performed by HPLC. The results of the study of the dissolution profiles of the drug Aulin, granules for oral suspension in pH 6.8, 7.5 and 7.8, where the active substance is not completely released. The addition of surfactants was used to increase the solubility of the drug. It has been experimentally confirmed that when using API nimesulide with a particle size D (90) = 64 μm, the release profiles are below the comparison drug. The similarity of the dissolution profiles of the test agent and the comparison drug provide API with a particle size D (90) < 30 μm. The dependence of the dissolution profile on the amounts of corn starch and macrogol 20 (polyethylene glycol) of cetostearyl ether is given, their optimal content in the composition of the drug is established. In the result of the work, the influence of research conditions on the dissolution profile of Aulin, granules for oral suspension, 100 mg/2 g was studied. pH 6.8 + 1% tween 80 and pH 7.4 + 0.5% tween 80 were chosen as optimal media. Experiments showed that the particle size of API nimesulide D (90) < 30 μm ensures compliance with the drug Nimesulide, granules for oral suspension, 100 mg/2 g by dissolution profiles. Increasing the amount of corn starch in the composition of the drug accelerates the dissolution of the granules and, as a consequence, raises the first points of the release profile of API. The use of 0.5% corn starch provides the dissolution profile closest to the comparison drug. To completely release API as a solubilizer, it is advisable to add 1% macrogol 20 (polyethylene glycol) cetostearyl ether.