APPLICATION OF TUMBLING MELT GRANULATION (TMG) METHOD FOR CONTROLLED ENTERIC-RELEASE BEADS BY COATING MIXTURE OF HYDROGENATED CASTOR-OIL AND HIGHER FATTY-ACID

Controlled-release beads which can release drugs faster in the higher pH region (pH 5-7.5) than in the acidic region (pH 1-5) were prepared using the newly developed tumbling melt granulation (TMG) method, in w hich process a powdered meltable material was coated onto the core bea ds without use of any organic solvent. This function could be obtained by using a mixture of hydrogenated castor oil (HCO) and higher fatty acids as coating materials, Controlled-release beads containing variou s kinds of drugs were prepared, Use of stearic acid as a fatty acid re sulted in excellent coating producibilities when the mixing ratio of s tearic acid (X-FA) was less than 30%. The dissolution rates determined in purified water, Ist. fluid, and 2nd fluid tended to increase with the increase of X-FA. This tendency was especially remarkable in the 2 nd fluid, The effect of the carbon number (12-22) of the fatty acid wa s then determined, The permeability coefficient, P, calculated from th e dissolution rate, decreased with the increase of carbon number, This seemed to be due to the difference of the release rate of fatty acid from the coating layer composed of HCO and fatty acid, Determination o f the dependency of P value on the DH of the dissolution medium showed that the P values changed little in the acidic region (pH 1.2 to 5.0) , but increased exponentially with an increase of pH over pH 5.5. Loga rithm of relative P values (P-pH/P-w:P-w means the P values in purifie d water) plotted against pH were distributed on the same line irrespec tive of fatty acid, An empirical equation which predicts the dissoluti on rates in the enteric medium was proposed using this relationship.