By Dileep R. Janagam and Tao L. Lowe
Birth control is still a major concern worldwide. Long-acting reversible contraceptives (LARCs) are commonly used birth control methods that provide contraception over a prolonged time period without the need of user activity, and are proven to be most effective in lowering the rates of unintended pregnancies. Currently available options include intrauterine system (IUS), intrauterine device (IUD), preformed implants, and injectable contraceptives. IUS, IUD, and preformed implants require a trained health care provider for implantation and removal, while the injectable LARCs are simple to administer and do not require any surgical procedures, therefore improving patient compliance.
More than 40 million women worldwide use injectable contraceptives, and their use is high in Africa and lower income Latin American countries. But in spite of this popularity, rates of discontinuation are also high for injectable LARCs due to non-adherence. The currently available injectable contraceptives can provide contraception for one or three months, thus requiring women to return to their health provider four to 12 times a year, which could be challenging in resource-limited settings of developing nations and may cause discontinuation and prolonged return to fertility due to users’ difficulty in complying with the multiple-injection schedule. Despite their effectiveness, presently available LARCs do not address women’s needs or specifications (PDF) which may be due to either poor accessibility or high cost. Hence there is a necessity for developing affordable injectable LARCs that can provide effective contraception for more than three months after a single shot.
To address the above-mentioned concerns, we are focused on the development of a polymer-based injectable in situ forming depot (ISD) system containing levonorgestrel (LNG) for contraceptive effect for six months or longer after a single injection. Our recently published Pharmaceutical Research article Long-Acting Injectable Hormonal Dosage Forms for Contraception reviews the strategies exploited in the past to develop injectable contraceptive formulations. The ISD systems are an attractive alternative to other sustained release formulations such as conventional preformed implants and microparticles for parenteral applications as they are relatively easy to manufacture and involve low cost of production. This would reduce the cost of birth control and expand the availability of contraceptive options globally.
But the major limitations associated with these long acting ISD systems are injectability and high initial burst. Most of these ISD systems are high viscous fluids and need a lower gauge needle (such as 18G/19G) for injection and this limits the patient compliance. Attempts made to lower the viscosity of the fluids would usually result in an increase in the initial burst and may also compromise the drug’s long-term release. Our research group tried to address these limitations in a unique and promising way:
Using a design rationale and integrative approach of combining a blend of poly(lactic-co-glycolic acid)/polylactic acid with different biodegradable properties, and using cosolvents such as N-methyl-2-pyrrolidone, triethyl citrate, benzyl benzoate, and varying the ratios of polymer, as well as solvent for dispersing/dissolving the LNG, we were able to improve the injectability of the formulations so they can be injected using a 21−23G needles and significantly minimize the initial burst. Further, the formulations have an advantage of reconstitution-free, versatility, and complete biodegradability. These unique formulations, when tested in rats using thinner (21−23G) gauge needles, have shown lower initial burst and also exhibited a constant LNG release profile to achieve plasma LNG levels within a range of 0.5-4 ng/mL for six months or longer. At the 2015 AAPS Annual Meeting and Exposition, we will present this work. This research suggests that the designed ISD formulations have great potential for developing future robust injectable LARC products that could improve access to family planning around the globe.