Injectable In Situ Forming Depot Systems for Long‐Acting Contraception

• Published in: Advanced biosystems 2017-10, Vol.1 (10), p.e1700097-n/a
• Main Authors: Janagam, Dileep R., Ananthula, Suryatheja, Chaudhry, Kamaljit, Wu, Linfeng, Mandrell, Timothy D., Johnson, James R., Lowe, Tao L.
• Format: Article
• Language: English
• Subjects: biodegradable polymers; injectable in situ forming depots; levonorgestrel; long‐acting contraception; sustained release
• ISSN: 2366-7478; 2366-7478
• DOI: 10.1002/adbi.201700097

Up to date, no long‐acting reversible contraceptive (LARC) is developed to be injectable through needles smaller than 18 G and can also provide contraception for more than 3 months after single injection. In this study, injectable polymeric in situ forming depot (ISD) systems are developed to have injectability through 21–23 G needles, and capability of sustained release of levonorgestrel (LNG) for at least 7 months in vitro and in vivo after single subcutaneous injection in rats. The systems are polymeric solutions composed of biodegradable poly(lactide‐co‐glycolide) and poly(lactic acid) polymers dissolved in a mixture of solvents like N‐methyl‐2‐pyrrolidone and benzyl benzoate or triethyl citrate. LNG released from ISD systems successfully suppressed the estrous cycle of rats at plasma concentration above 0.35 ng mL−1. At the end of the treatment, when LNG plasma concentration drops down to be nondetectable, predictable return of fertility is observed in rats. The designed ISD systems have great potential to be further developed into robust injectable LARCs that can be injected through a 21 G or smaller needle and achieve a variety of contraception durations with high patient compliance and low cost. The development of polymeric in situ forming depot systems that are injectable through 21–23 G needles, and sustain the release of levonorgestrel for at least 7 months after single subcutaneous injection in rats is reported. These formulations are easy to manufacture with low costs, easy to administer with high patient compliance, and completely biodegradable without the need of surgical removal.