An Accelerated Release Study to Evaluate Long-Acting Contraceptive Levonorgestrel-Containing in Situ Forming Depot Systems

Abstract

Biodegradable polymer-based injectable in situ forming depot (ISD) systems that solidify in the body to form a solid or semisolid reservoir are becoming increasingly attractive as an injectable dosage form for sustained (months to years) parenteral drug delivery. Evaluation of long-term drug release from the ISD systems during the formulation development is laborious and costly. An accelerated release method that can effectively correlate the months to years of long-term release in a short time such as days or weeks is economically needed. However, no such accelerated ISD system release method has been reported in the literature to date. The objective of the current study was to develop a short-term accelerated in vitro release method for contraceptive levonorgestrel (LNG)-containing ISD systems to screen formulations for more than 3-month contraception after a single subcutaneous injection. The LNG-containing ISD formulations were prepared by using biodegradable poly(lactide-co-glycolide) and polylactic acid polymer and solvent mixtures containing N-methyl-2-pyrrolidone and benzyl benzoate or triethyl citrate. Drug release studies were performed under real-time (long-term) conditions (PBS, pH 7.4, 37 °C) and four accelerated (short-term) conditions: (A) PBS, pH 7.4, 50 °C; (B) 25% ethanol in PBS, pH 7.4, 50 °C; (C) 25% ethanol in PBS, 2% Tween 20, pH 7.4, 50 °C; and (D) 25% ethanol in PBS, 2% Tween 20, pH 9, 50 °C. The LNG release profile, including the release mechanism under the accelerated condition D within two weeks, correlated (r2 ≥ 0.98) well with that under real-time conditions at four months.

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.…”

Injectable Vaginal Hydrogels as a Multi-Drug Carrier for Contraception

“…The PLGA-PEG-PLGA thermo-gel markedly extended the release of LNG, which was promising for long-term contraception and fertility control [38]. The poly(lactide-co-glycolide) and polylactic acid polymer and a solvent mixture containing N-methyl-2-pyrrolidone and benzyl benzoate or triethyl citrate was be used as LNG-containing injectable in situ forming depot (ISD) system, then a long-time release of LNG was accomplished [39]. The star-shaped poly(D,L-lactic-co-glycolic acid)-b-methoxy poly(ethylene glycol) (4sPLGA-mPEG) block copolymer showed tuning sol-gel transition, controllable biodegradability, and excellent biocompatibility in vitro and in vivo, and also showed potential in many biomedical applications in our previous reports [40][41][42].…”

Enhanced Bioavailability and Anticancer Activity of Vitamin Analogs

“…They have been shown significant efficiency in cancer and also in other forms of diseases [20][21][22][23][24][25]. Formulation type can alter their biological activity in favor of cancer treatment [26][27][28][29].…”