DEVELOPMENT OF BROMOCRIPTINE MESYLATE SELF-MICROEMULSIFYING SYSTEM TABLET

Abstract

The poor water solubility and high hepatic metabolism cause low oral bioavailability of bromocriptine mesylate (BM) used for Parkinson’s treatment. Therefore, self-microemulsion (SME) tablets were developed to improve solubility, stimulate lipoprotein synthesis which promote lymphatic transport, avoid hepatic metabolism and target drug to brain. Natural oils composed of high purity of long chain fatty acids were selected and the effect of nonionic surfactants and co-surfactants on the SME formation ability was investigated. The SME liquid was prepared, adsorbed by solid carriers, Aerosil®200, Aeroperl®300 or NeusilinUS2® at suitable ratios, yielding SME powders and then compressed as tablet. The in vitro cell culture studies were investigated in Caco-2 cells and co-culture of endothelial cells (bEnd.3) and astrocytes (CTX TNA2). The results indicated that the marketed tablet gave a significantly higher drug permeated through Caco-2 cells than those obtained from SME tablet, however, the higher drug uptake was found when SME formulations were given (p<0.05). In addition, the fluorescein loaded SME tablet showed the higher cellular uptake than fluorescein loaded in oil or surfactant. The highest lipoprotein synthesis expressing as content of apolipoprotein B found in secreted chylomicron and drug uptake in co-culture of bEnd.3 and CTX TNA2 were obtained from drug loaded SME tablet compared to marketed tablet (p<0.05). Therefore, the SME tablet might potentially deliver BM to the brain via lymphatic transport by increasing the lipoproteins synthesis.