Release of small water-soluble drugs from multiblock copolymer microspheres: a feasibility study

Poly(ethylene glycol)-terephthalate/poly(butylene terephthalate) (PEGT/PBT) multiblock copolymer was investigated as a possible matrix for controlled delivery of small water-soluble drugs. Two molecules were selected as sustained release candidates from microspheres: leuprorelin acetate (peptide of Mw = 1270 D) and vitamin B-12 (MW = 1355 D). First, vitamin B-loaded microspheres were prepared using a double emulsion method and preparation parameters were varied (surfactant in the first emulsion and copolymer composition). The resulting microsphere structure, entrapment efficiency and release rate were evaluated. Vitamin B-12-loaded microsphere parameters could easily be tailored to achieve specific requirements. The addition of surfactant in the first preparation process led to a significant increase of the microsphere entrapment efficiency, whereas the decrease of the PEGT copolymer content allowed the release rates from microspheres to be precisely decreased. However, leuprorelin acetate-loaded microspheres did not show the same characteristics when prepared with the same parameters, possibly because of a high water solubility discrepancy between the vitamin B-12 and the peptide. This study shows the suitability of PEGT/PBT microspheres as a controlled release system for vitamin B-12, but not for leuprorelin acetate. It also underlines the necessity of tailored development for each individual drug and emphasizes the risk of using model molecules. (C) 2002 Elsevier Science B.V. All rights reserved.