In situ forming drug delivery system is prepared by phase inversion technique using poly (D,L-lacticco-glycolide) and leuprolide acetate dissolved in N-methyl-2-pyrrolidone. The effects of ethyl heptanoate and glycerol additives are important determinant as rate modifying agents on the drug release kinetics in biodegradable in situ forming porous systems of poly(D,L-lactide-co-glycolide) (PLGA) in N-methyl-2-pyrrolidone (NMP). The release performance and porous structure morphology are investigated by scanning electron microscopy and UV-visible spectroscopy techniques to study the effect of additives. The experimental results exhibit the crucial role of ethyl heptanoate and glycerol at different loadings (1, 3, and 5% w/w) on release profile of leuprolide acetate loaded on poly(D,L-lactide-co-glycolide)hydroxylated (PLGA-H). Both additives at different concentrations reduce the burst effect, while increasing duration of drug release. Ethyl heptanoate, however, shows stronger effect than glycerol. The results of morphological studies show that ethyl heptanoate reduces the porosity of the polymer surface and interconnected tear-like structures of the bulk disappear while the sponge-like structures are observed. In this system glycerol reduces the surface porosity intensively, while the interconnected tears change into channel-like structures. Therefore, morphological results confirm the effect of additives on leuprolide release profile.

A poly (lactide-co-glycolide) (PLGA) implant was used to control the release profile of leuprolide acetate (LA) drug. The system is an in-situ polymeric precipitation system. And the formulation consisted of PLGA polymer, LA drug and N-methyl-2-pyrrolidon solvent with no additives. First, the formulation was injected into PBS solution for in-vitro studies and then it was administered to the animal models (female rats) for in-vivo release studies. The release profiles of leuprolide acetate were measured by UV spectrophotometry for a period of 28 days. The initial burst release of LA was 14% in in-vitro whereas it was 7% in in-vivo. In-vitro and in-vivo release profiles of LA had similar trends after 72 hours. However, the rate of LA release was slower in-vivo. This might be attributed to the limited diffusion process of solvent and the drug molecules. This could be due to presence of an additional pressure caused by the surrounding tissue and also the presence of small amount of water between cells in the subcutaneous site. Cross-section and surface of the implants were studied via scanning electron microscopy. Morphology of both in-vitro and in-vivo implants confirmed the release behaviours. No toxicity effects were reported in the histopathological assay. Furthermore, the pharmacological analysis showed more inactive ovaries due to release of LA.

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