Desarrollo de un coprocesado de un fármaco antimicótico de velocidad de disolución mejorada mediante la técnica de granulación por fusión en un mezclador de alto corte

Abstract

Melt granulation(MG)is a simple process that involves the uniform mixture of active ingredients with a melted polymeric carrier, but it also can enhance the biopharmaceutical properties of a drug by augmenting its dissolution rate, thus its absorption. The current research focuses on the development of a co-processed ketoconazole having higher aqueous dissolution rate compared to its pure form,through the application of MG technology. A measure of how the type and proportion of polymeric carriers affect crystallinity and dissolution rate of ketoconazoleco-processed materials was performed. Materials were prepared by MG in a high-shear mixer using co-povidone (Kollidon®)VA 64 and HPMCAS HF as polymeric carriers, and PEG 1450 (Kollisolv®),and triethyl citrate as plasticizers. The co-processed ketoconazole materials exhibited miscibility in the polymeric systems,as indicated by the reduction in the enthalpyof fusion.Drug crystallinity was significantly reduced in the HPMCAS HF polymeric system,confirmed by XRPD and ATR-FTIRstudies. Dissolution rate was found to be enhanced by using a higher drug concentration in a co-povidoneVA 64environment;contrarily,for HPMCAS HF, a higher drug dilution was observed to favor dissolution rate. MGis a handy, low-cost technology to develop dissolution-enhanced co-processed active pharmaceutical ingredients,spotting specific carrier-drug interactions. MG yields scalable-proven processes, raising interest on its applications on optimizing the therapeutic efficacy of drugs. Ultimately, the use of this technology for dissolution enhancement could bring lower-cost, high-efficiency drugs aiming to improve the quality of life for patients.