Mats Ove Johansson

In vitro release characteristics of a membrane-coated pellet formulation — influence of drug solubility and particle size

Abstract The impact of drug solubility and particle size on the in vitro release characteristics of membrane-coated pellets has been investigated for the metoprolol salts, sorbate, benzoate, succinate and fumarate. Three well-defined size fractions of small spherical pellets were prepared for each salt and coated with a membrane of ethylcellulose and hydroxypropyl methylcellulose (proportion 3:1). The particle diameter, surface area, volume and apparent density were determined for each fraction of coated pellets and their drug release properties were characterized by an initial lag-time, a constant release rate phase and a final declining release rate phase. Both the particle size and drug solubility were shown to be important for the release properties of the pellets. Thus, the constant release rate was approximately proportional to the surface area of the pellets over the entire solubility range (~ 20–500 mg/ml). All three phases of the drug release curve were strongly influenced by the drug solubility. This was explained on the basis of the different concentration gradients over the membrane as well as by osmotic effects. Although the release rate was shown to be markedly affected by the osmotic pressure, evaluation of the release kinetics did not reveal osmotic pumping to be the major mechanism for the release. Also, diffusion appears to be important for the drug release from the investigated formulations.