Didanosine (ddI) is a water-soluble antiretroviral used in the treatment of HIV that undergoes fast gastric degradation to an inactive hypoxanthine. Therefore, its oral bioavailability is relatively low (20-40%). In this work, we investigated for the first time a scalable open-loop spray-drying method with co-current flow for the encapsulation of ddI (model drug) within particles of the biocompatible polyester poly(epsilon-caprolactone). The average diameter of the particles was 36-118 μm and the morphology spherical. The encapsulation efficiency ranged from 60% to 100% with yields of up to 65%. ATR/FT-IR analysis indicated that most of the drug was encapsulated within the particles. In vitro release assays showed that the particles released the drug within 120 min. Finally, oral administration to rats led to a statistically significant 2.5-fold increase of the bioavailability with respect to a ddI aqueous solution, highlighting the potential of this technology to encapsulate efficiently other hydrophilic antiretrovirals and, by doing so, to overcome different biopharmaceutical drawbacks associated with the oral administration.
Keywords: Didanosine (ddI); Enhanced oral bioavailability; HIV therapy; Poly(epsilon-caprolactone) microparticles; Spray-drying.
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