Formulation of Monodisperse Alginate (Micro) Spheres Containing Tenofovir for Extended Release Dosage Form

Abstract

Tenofovir (TF) belongs to a class of antiretroviral drugs known as nucleotide analogue reverse transcriptase inhibitors (NRTIs) used in the treatment of human immunodeficiency virus 1 (HIV-1) and hepatitis B. Despite its safety and effectiveness, TF oral administration limited by several factors : low bioavailability (25%), adverse effects like decrease in bone mineral density and severe renal adverse events, including fanconis syndrome due to frequent dosing, and high circulating plasma levels. By developing particulate drug carriers it is possible to achieve effective plasma concentration without significant fluctuation, to avoid sub-therapeutic or toxic plasma concentrations, to achieve an effective therapy with a low dosage and to reduce the dosage frequency. TF loaded floating particulate drug carriers for control release medication were designed and constructed to prolong the retention in the stomach and to facilitate drug absorption over a prolonged period of time using Extrusion ionic gelation technique employing sodium alginate alone and in combination with MC, HPMC K100M, HPMC K15M. The drug release for the optimized formulation, F10, followed first order kinetics and Higuchi plot of F10 formulation showed an R2 value of 0.9582. The data were fitted to the Korsmeyer-Peppas equation and the values of diffusion exponent ‘n’ for the batch F10 was 0.623 which indicated the drug release by Non-Fickian diffusion, suggesting that the diffusion along with erosion/swelling plays an important role in extending the drug release. Surface morphology of microspheres was found to be Smooth. These results suggested that the TF microbeads are promising and should be investigated further in the near future as an effective oral delivery system.