Executive Summary : | Globally, 121 million unintended pregnancies are reported every year with an average of 3,31,000 cases every day as per 2022 report. More than 60% of unintended pregnancies end up in abortion. From 2007 to 2011, 67% of abortions in India were classified as unsafe leading to the greater chances of maternal mortality. Therefore, use of modern contraceptive methods is key to prevent the root cause i.e., unintended pregnancy. Among variety of methods, progestogens like Levonorgestrel administration after unprotected intercourse has gained much interest in preventing pregnancy. However, the currently marketed injection form (pain, requirement of healthcare professional, and patient inconvenience) and oral pill form of Levonorgestrel (lack of solubility leads to poor bioavailability and gastrointestinal tract related side effects over a long period of use) are facing several issues. Due to which, transdermal Levonorgestrel patch has come into lime light in developed countries. But they did not show up in India due to their high cost, which makes them unaffordable for low- and middle-income families. Thus, a low-cost, robust, day-long deliverable, and self-administrable novel transdermal formulation containing Levonorgestrel is in greater demand. In this work, for the first time, we will formulate a novel umbilical route administrable transferosome-based in situ gel containing Levonorgestrel for a day-long delivery to prevent pregnancy. Further, we will investigate the potential of umbilical skin tissues to deliver drugs into systemic circulation in comparison to other skin sites. Computational modelling tools will be used to design a most appropriate transferosomal in situ gel formulation composition. The central composite design (Experimental design) will be adopted to optimize the concentration of each component in the transferosomes formulation. The properties and performance of prepared transferosomes formulation will be evaluated for particle size, elasticity behaviour, morphology, entrapment efficiency, and skin permeability. The stability and skin irritation studies of transferosomal in situ gel formulation as per ICH Q1A R2 guidelines will be conducted to ensure the product shelf-life and safety. Lastly, the main part of this whole study i.e., in vivo pharmacokinetic study using pigs will be conducted to investigate the potential of umbilical route to deliver drugs into systemic circulation compared to other skin sites (arms and legs). Up on completion of these objectives, a cost-effective, day-long deliverable, and self-administrable transdermal formulation for preventing pregnancy can hit the market with easy affordability by low- and middle-income family women. This could potentially bring down the side effects associated with current most widely used oral contraceptive pills. Finally, this project would reduce the rate of unintended pregnancies, unsafe abortions, and maternal death, which is one of the major issues in India. |