Hydrophobic ion pair formation between leuprolide and sodium oleate for sustained release from biodegradable polymeric microspheres

Leuprolide acetate, an analogue of luteinizing hormone-releasing hormone (L H-RH), was hydrophobically ion paired with a long chain fatty acid, sodium oleate, in an aqueous solution. Solution behaviors of the complex formed be tween leuprolide and sodium oleate were investigated in terms of aqueous so lubility, turbidity, particle size, and zeta potential as a function of mol ar ratio between the two species. II was found that with increasing the sto ichiometric molar amounts of sodium oleate to leuprolide approached up to 2 .5-3, the solution became gradually turbid with increasing particle sizes, indicating leuprolide precipitation as a result of hydrophobic ion pairing. On the other hand, beyond that critical molar ratio range, the solution tu rned into clear with much reduced particle size, indicative of micelle form ation. The hydrophobically modified leuprolide-oleate complex was lyophiliz ed and directly encapsulated within biodegradable poly(D,L-lactic-co-glycol ic acid) (PLGA) microspheres via a single oil-in-water (O/W) emulsion metho d. Microsphere morphology, leuprolide release behavior, and polymer mass er osion profiles were examined in comparison to the PLGA microspheres prepare d with free leuprolide. (C) 2000 Elsevier Science B.V. All rights reserved.