In-vitro/In-vivo comparison of leuprolide acetate release from an in-situ forming plga system

Abstract

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.

An Overview of In Situ Gel Forming Implants: Current Approach Towards Alternative Drug Delivery System

“…Then these collected samples were deprotinised by using acetonitrile and then analyzed by using different analytical techniques like UV-spectroscopy, mass spectroscopy or ultra-performance liquid chromatography mass spectroscopy to obtain the data about plasma drug concentration of drug at different time interval. From obtained plasma drug concentration different pharmacokinetic parameters such as maximum plasma concentration, maximum time to reach maximum plasma concentration (t max ) and mean residence time can be determined [45][46][47][48][49][50][51][52][53][54] . CONCLUSION: From overall discussion it is concluded that the in-situ forming implants (ISFI) are the alternative drug delivery system to the frequently administered parental injections.…”

In situforming poly(lactic acid-co-glycolic acid) implants containing leuprolide acetate/β-cyclodextrin complexes: preparation, characterization, andin vitrodrug release

“…An undesirable initial burst release may exhaust the loaded drug from implants too rapidly and cause severe toxicity problems. It can also lead to an overall 3 shorter release period and subsequently less therapeutic efficiency and cost-effectiveness [1,4].…”

“…Through past years, we have focused on the development of PLGA-based ISIs for LA delivery [3,4,13,14]. Bodmeier et al [15][16][17] have also done several researches about LA-loaded in situ forming PLGA microspheres.…”

In situ forming PLGA implant for 90 days controlled release of leuprolide acetate for treatment of prostate cancer

“…A wide variety of polymeric substances have been employed for such in situ forming systems. However, biodegradable polyesters of hydroxy acids, such as poly(lactic‐co‐glycolic acid) (PLGA), and related polymers have been particularly prominent owing to their high biocompatibility . In addition, implants made from these polymers can be tailored so that the duration of drug release can span from weeks to months.…”

“…However, biodegradable polyesters of hydroxy acids, such as poly(lactic-co-glycolic acid) (PLGA), and related polymers have been particularly prominent owing to their high biocompatibility. [7,8] In addition, implants made from these polymers can be tailored so that the duration of drug release can span from weeks to months. It is well known that PLGA undergoes nonenzymatic hydrolysis to lactic and glycolic acids, which are eventually metabolized to carbon dioxide and water.…”