Atazanavir-Loaded Crosslinked Gamma-Cyclodextrin Nanoparticles to Improve Solubility and Dissolution Characteristics.

OBJECTIVES

Atazanavir sulfate (AS), a Biosafety Cabinet (BCS) class II antiretroviral drug, shows dissolution rate-limited bioavailability, therefore, it is necessary to improve its solubility and oral bioavailability. The present investigation is intended to improve the aqueous solubility by developing AS-loaded nanoparticles (ASNPs). Additionally, the immediate release formulation of AS capsules has gastrointestinal side effects such as nausea and abdominal pain, cardiovascular side effect, abnormal cardiac conduction, toxic effects on kidney and liver such as nephrolithiasis, hyperbilirubinemia, and jaundice. Therefore, ASNPs were designed to release the drug slowly for 12 h, so that these side effects could be reduced.

MATERIALS AND METHODS

ASNPs were prepared using gamma-cyclodextrin (γ-CD) and the crosslinker dimethyl carbonate were characterized by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) to check the crystal characteristics of AS upon entrapment in NPs. Entrapment efficiency (EE), particle size, morphology, solubility, and dissolution behavior were also determined.

RESULTS

EE%, particle size, and zeta potential varied from 14.38 ± 0.16 to 75.97 ± 0.28%, 65.4 ± 1.25 nm to 439.6 ± 2.21 nm, and 28.3 ± 0.1 mV to 41.0 ± 0.3 mV, respectively. XRD and DSC confirmed the transformation of the crystalline AS to amorphous in NPs. There was 11.717 folds rise in AS solubility in water from NPs. The formulation having AS: γ-CD, 1:1 at 10 mg/mL, depicted 88.55 ± 0.58, 91.23 ± 0.80, and 86.8 ± 0.65% drug release in water, acid buffer, and phosphate buffer, respectively, in 12 h.

CONCLUSION

Solubility enhancement could be attributed to the decrease in crystallinity of atazanavir, when dispersed in NPs.