In light of the increasing worldwide AIDS pandemic, there is a continuing need to develop new prevention strategies to inhibit the transmission of HIV-1. In the absence of a successful vaccine, topical microbicides represent the best strategies to reduce the epidemic. Following the success of HIV therapeutic cocktail strategies, combinations of microbicides including nucleotide reverse transcriptase inhibitors (NtRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) may offer significant protection from infection over single agents. We have developed a combination microbicide gel formulation for the delivery of IQP-0528, a novel NNRTI, and tenofovir (TFV), a NtRTI. Gel formulations were evaluated based on quantitative viscoelastic and physiochemical evaluations defined by a target product profile (TPP). For the majority of the evaluations, the gel formulations behaved similarly; all showed shear thinning behavior, were stable, nontoxic, and active against HIV-1 infection. Gel formulation F2759 displayed increased drug release of 289 ± 100 µg/(cm2 h1/2) and a tissue permeability of 60 times the half maximal effective concentration (EC50) of TFV and 800 times the EC50 of IQP-0528. In addition, F2759 showed osmolality within TPP and the highest performance in gel spreading. We have identified a gel formulation to deliver a combination microbicide of IQP-0528 and TFV that has significant potential to prevent infection of HIV-1.
Ham, A.S.; Ugaonkar, S.R.; Shi, L.; Buckheit, K.W.; Lakougna, H.; Nagaraja, U.; Gwozdz, G.; Goldman, L.; Kiser, P.F.; Buckheit Jr., R.W. Development of a combination microbicide gel formulation containing IQP-0528 and tenofovir for the prevention of HIV infection. Journal of Pharmaceutical Sciences (2012) 101 (4) 1423-1435. [DOI: 10.1002/jps.23026]