Solid solutions vs. solid dispersions: the impact of formulation parameters

Abstract

Matrix films were prepared with drugs with different aqueous solubility (metoprolol tartrate, ibuprofen and diclofenac Na) and different polymers (ethylcellulose, Eudragit RS and Eudragit RL). Solid solutions (drug dissolved) and solid dispersions (drug dispersed) were obtained. The drug release was studied as a function of drug type and loading, additive type and amount and polymer type. Drug release from the matrices was not in accordance with drug aqueous solubility, but rather with the physical state of the drug in the matrix. Increasing the drug loading increased the drug release rate in a monotonical fashion for the solid solution. In contrast, increasing the drug loading with the solid dispersion had almost no effect until 30 %. An increase in speed was only registered after the drug release significantly increased. The addition of hydrophilic additives mainly increased the initial phase of the release profile, with no effect on the plateau. On the contrary, polyethylene glycol 1500 was shown to decrease the release of diclofenac Na due to entrapment of the drug in the hydrophilic additive domains. The effect of polymer type on ibuprofen release correlated well with the partition of the drug into the polymer. In the case of metoprolol tartrate, drug release was much faster from Eudragit RS than EC matrices due to the formation of an amorphous mixture with Eudragit RS polymer.