In-situ forming gel-like depot of a polyaspartamide-polylactide copolymer for once a week administration of sulpiride.

Objectives: An in-situ forming gel-like depot, prepared by using an appropriate polyaspartamide-polylactide graft copolymer, has been employed to release in a sustained way sulpiride.

Methods: α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide-g-polylactic acid (PHEA-g-PLA) has been used as a polymer component. Its physicochemical properties make possible to dissolve it in N-methyl-2-pyrrolidone, with the obtainment of a solution able to form a gel-like depot once injected into a physiological medium. Cell compatibility of PHEA-g-PLA depot has been investigated, using murine dermal fibroblasts as cell model. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt assay and fluorescence microscopy have been employed to evaluate cell viability and morphology after contact with PHEA-g-PLA depot. Pharmacokinetic parameters of sulpiride released from depot have been determined following subcutaneous administration to rabbits and compared with corresponding parameters following administration of free sulpiride solution.

Key Findings: It has been demonstrated that the system does not affect significantly the viability of fibroblasts and is able to sustain the release of sulpiride until a week, with a burst effect dependent on the initial weight ratio polymer/drug.

Conclusion: In-vivo release profiles and pharmacokinetic parameters suggest that PHEA-g-PLA depot could have interesting clinical applications for a once a week administration of poorly soluble drugs to humans or animals.