Enhancing Solubility and Bioavailability of Adefovir Dipivoxil to Treat Viral Infections

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2019-08-14
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Tabula, Lindlelyn
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Nerurkar, Vivek
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Hepatitis B virus is known to cause hepatocellular carcinoma in humans. HBV infection affects more than 250 million individuals globally and approximately 1.25 million individuals in the USA. Adefovir dipivoxil is a reverse transcriptase inhibitor, which is currently approved for the oral treatment of chronic HBV infection. The current oral bioavailability of adefovir is 59%% meaning only 59% of the orally administered adefovir dipivoxil is efficacious. While adefovir dipivoxil is clinically effective for the treatment of HBV, severe nephrotoxicity is one of the major side effects associated with adefovir dipivoxil. The improvement in the oral bioavailability of adefovir dipivoxil is expected to reduce the therapeutic dose of adefovir dipivoxil, which will, in turn, reduce the dose-related nephrotoxicity of adefovir dipivoxil. The development of oral formulations that are capable of enhancing oral bioavailability of adefovir dipivoxil, will reduce the required therapeutic dose of adefovir dipivoxil and the dose-related nephrotoxicity. The project involved pharmaceutical characterization of adefovir dipivoxil, its analysis by the UV-Vis spectrophotometry. Furthermore, the project will include studies to ascertain the feasibility of developing adefovir dipivoxil-cyclodextrin complexes and solid dispersions. The adefovir dipivoxil-cyclodextrin complexes and solid dispersions will be characterized by several methods to ensure the complexation such as phase solubility studies and in vitro dissolution. This project may significantly reduce the adverse effects associated with chronic hepatitis B treatment with orally administered adefovir dipivoxil. In the grand scheme of things, the successful completion of this project will lead to the development of adefovir dipivoxil-cyclodextrin complex or solid dispersions, which can be further transformed into pharmaceutically acceptable dosage forms such as tablets or ophthalmic formulations.
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Adefovir Dipivoxil
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Attribution-NonCommercial-NoDerivs 3.0 United States
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