Human immunodeficiency virus (HIV) is a retrovirus that can cause acquired immunodeficiency syndrome (AIDS), a condition in which immune system failure can lead to life threatening infections, cancer or even neurological problems. Although HIV has these drastic effects, to date no drug has been developed to cure it and taking a single medication is not enough to suppress this virus. Three-drug combinations have the best efficacy for controlling the virus and protecting the immune system. Therefore, 3 drug combinations of ritonavir, etravirine and efavirenz amorphous solid dispersions (ASDs) were prepared with cellulose esters in order to prepare an higher bioavailability formulations for daily application, to enhance patient convenience and compliance and prevent viral adaptation due to missed doses. Although oral administration is favored, the poor solubility of HIV drugs (0.1-10 ug/ml) leads to low bioavailability due to their crystallinity and hydrophobicity. For this reason, ASDs of HIV drugs have been implemented to suppress crystallinity of these poorly water-soluble and thereby enhance dissolution rate and bioavailability. Thus, cellulose acetate suberate (CASub), cellulose acetate adipate propionate (CAAdP), 6-carboxyl cellulose acetate butyrate (CCAB) and carboxymethylcellulose acetate butyrate (CMCAB) micro-milled solvent cast films were prepared in order to increase dissolution rate of ritaonavir, etravirine and efavirenz. In some cases, vitamin E TPGS were also added to the formulations in amounts that would generate concentrations above the critical micelle concentration in order increase drug release. The amorphous solid-state properties of these formulations were shown by XRD. By dissolution studies, it was shown that 3 drugs were released at small intestine (pH 6.8) slowly (without any burst effect) at a concentration higher than the crystalline drug itself. Accordingly, these formulations have great potential to increase the bioavailability of the three drugs, releasing them over a 10-hour period.

Development of 3 drug combination formulations with cellulose esters for the effective oral treatment of HIV

249th National Meeting (2015)

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