Aqueous HPMCAS coatings: Effects of formulation and processing parameters on drug release and mass transport mechanisms

Abstract

The major aim of the present work was to study the effects of various formulation and processing parameters on the resulting drug release kinetics from theophylline matrix pellets coated with aqueous hydroxypropyl methylcellulose acetate succinate (HPMCAS) dispersions. The plasticizer content, coating level and curing conditions significantly affected the release patterns in 0.1 M HCl, whereas no major effects were observed in phosphate buffer, pH 7.4. Due to the significant size of the HPMCAS particles (being in the micrometer range), their coalescence was particularly crucial and not complete upon coating. Consequently, at low coating levels continuous water-filled channels connected the bead cores with the release medium through which the drug could rapidly diffuse, resulting in high release rates even at low pH. In contrast, at high coating levels such continuous connections did not exist (due to the increased number of polymer particle layers), and drug release was controlled by diffusion through the macromolecular network resulting in much lower release rates in 0.1 M HCl. Importantly, pellet curing at elevated temperature and ambient relative humidity or exposure to elevated relative humidity at room temperature did not significantly alter the microstructure of the coatings, leading to only slightly decreased drug release rates. In contrast, pellet curing at elevated temperature combined with elevated relative humidity induced significant further polymer particle coalescence, resulting in a change of the underlying drug release mechanism and significantly reduced drug release rates.