Development and evaluation of sustained-release ibuprofen-wax microspheres. II. In vitro dissolution studies.
A modified USP paddle method using minibaskets was used to study the effects of various formulations on in vitro dissolution of ibuprofen microspheres. Formulations containing waxes such as paraffin or ceresine wax without modifiers exhibited very slow dissolution profiles and incomplete release, which did not improve with increased drug loading or the preparation of smaller microspheres. The addition of modifiers such as stearyl alcohol and glyceryl monostearate greatly increased the dissolution rate, with 20% (w/w) near the optimum for predictable dissolution. Higher drug loading and decreased microsphere size increased the dissolution rate from microspheres containing modifier. Optimum formulations contained ceresine wax or microcrystalline wax and stearyl alcohol as a modifier, with a drug content of 17%. An increase in the encapsulation dispersant concentration had little effect on the dissolution profiles. The dissolution data from narrow size fractions of microspheres indicated spherical matrix drug release kinetics; the 50% dissolution time decreased with the square of the microsphere diameter. With appropriate modifiers, wax microsphere formulations of drugs with solubility characteristics similar to those of ibuprofen can offer a starting basis for predictable sustained release dosage forms.
Adeyeye
C M
CM
Department of Pharmaceutical Chemistry and Pharmaceutics, School of Pharmacy, Duquesne University, Pittsburgh, Pennsylvania 15282.
Price
J C
JC
D003692:Delayed-Action Preparations; D006863:Hydrogen-Ion Concentration; D007052:Ibuprofen / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008863:Microspheres; D010316:Particle Size; D012995:Solubility; D014885:Waxes / Q000737:chemistry
D003692:Delayed-Action Preparations; D014885:Waxes; D007052:Ibuprofen