High-amylose sodium carboxymethyl starch matrices for oral, sustained drug release: development of a spray-drying manufacturing process

摘要

Context: High-amylose sodium carboxymethyl starch (HASCA) was recently proposed as a material for oral, sustained drug-release tablets prepared by direct compression. It was produced on a pilot scale, but appeared to be unsuitable for tableting and sustained drug release. Pilot-scale dry powder HASCA was dispersed in hot water and then precipitated with ethanol to give a dry powder presenting the required properties, but very high volumes of ethanol were used to recover the product. Objective: A process was therefore designed to transform totally amorphous pregelatinized HASCA by spray-drying into a suitable sustained drug-release excipient for matrix tablets while decreasing ethanol quantities. Results and discussion: During the first manufacturing step, that is, heating of the initial hydro-alcoholic suspension, powder and water concentrations are key parameters for the acquisition of excellent binding properties. Hence, a variable ratio of amylose Vh, a crystalline polymorph of amylose, to the amorphous form, is observed depending on the key parameter values. As the most crystalline samples give the weakest tablets, binding properties do not appear to be linked to the presence of a Vh form of amylose. On the other hand, a high water concentration results in excessive tablet strength, that is, inverse conditions leading to the appearance of a Vh form of amylose. Finally, variations in hydro-alcoholic composition appear to affect only tableting properties and do not influence the drug-release rate. Conclusion: A process designed to transform totally amorphous pregelatinized HASCA by spray-drying is proposed for easier, economical industrial HASCA production.