Release of diclofenac (salt or acid) from lipid microspheres prepared by ultrasound atomization

The aim of this work was to elucidate the underlying drug release mechanisms from lipidic matrix microspheres, using two chemical forms of diclofenac (acid or salt) as model drug; and Compritol and Carnauba wax, either alone or together with varying amount (10-30 % w/w) stearic acid. The systems prepared as physical mixtures were obtained as solid dispersion (melting method) in the form of microspheres by atomization assisted by ultrasound. The effects of different formulations on the resulting drug release kinetics in 0.1 N HCl and phosphate buffer pH 7.4 were studied. Release of acidic diclofenac - Lipid matrix prevents the release of the drug at low pH. The systems contain at least 20% of ionisable diclofenac and pH 7.2 of the buffer should be enough to start its ionization and dissolution, which on the contrary seems to be driven in the presence of stearic acid; in the presence of 30% stearic acid release is complete after 1 h. Release of the diclofenac salt - The release at acidic pH is null, while the salt is rapidly released from the lipid matrix at pH 7.2 in the presence of compritol; from carnauba wax matrix it needs the presence of stearic acid. In each case the release of the salt is faster than that of the acid, where dissolution had to be mediated by ionization: this reaction rate proved to be slowed down by the proximity of the lipid matrix. Treating the experimental data in the terms of Peppas equation: Mt/M∞ = ktn, we found n = 0.57 for the release from pure compritol (0.71 for carnauba wax), based on a diffusion mechanism. While in the presence of stearic acid n was found 0.83 (0.75 for carnauba wax), indicating erosion and diffusion operating together for the release of the drug from microspheres, in agreement with the photos taken at SEM.