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Atazanavir-Loaded Crosslinked Gamma-Cyclodextrin Nanoparticles to Improve Solubility and Dissolution Characteristics
Darshana Dhabliya1, Shagufta Abdul Qaiyum Khan1, Minal Umate1
1Institute of Pharmaceutical Education and Research, Maharashtra, India.
Turkish Journal of Pharmaceutical Sciences
|September 1, 2022
Summary
Atazanavir sulfate nanoparticles (ASNPs) were developed to improve solubility and reduce side effects. The study demonstrated a significant increase in solubility and sustained drug release over 12 hours.
Area of Science:
- Pharmaceutical Nanotechnology
- Drug Delivery Systems
- Antiretroviral Therapy
Background:
- Atazanavir sulfate (AS) exhibits poor aqueous solubility and dissolution-limited bioavailability.
- Immediate-release formulations of AS are associated with significant gastrointestinal, cardiovascular, and organ-specific toxicities.
- Developing novel drug delivery systems is crucial for enhancing AS efficacy and patient safety.
Purpose of the Study:
- To develop atazanavir sulfate-loaded nanoparticles (ASNPs) to improve aqueous solubility and oral bioavailability.
- To engineer ASNPs for sustained drug release over 12 hours, aiming to mitigate AS-associated side effects.
- To characterize the physicochemical properties and drug release profile of the developed ASNPs.
Main Methods:
- ASNPs were prepared using gamma-cyclodextrin (γ-CD) and dimethyl carbonate as a crosslinker.
- Nanoparticle characterization included differential scanning calorimetry (DSC), X-ray diffraction (XRD), entrapment efficiency (EE), particle size, zeta potential, and morphology analysis.
- In vitro drug release studies were conducted in water, acid buffer, and phosphate buffer over a 12-hour period.
Main Results:
- Characterization confirmed the transformation of crystalline AS to an amorphous state within the nanoparticles.
- A significant 11.717-fold increase in AS aqueous solubility was achieved with the nanoparticle formulation.
- The optimal AS:γ-CD (1:1) formulation exhibited high entrapment efficiency and sustained drug release (86-91%) over 12 hours across different media.
Conclusions:
- The developed ASNPs effectively enhance the aqueous solubility of atazanavir sulfate.
- The amorphous state of AS within nanoparticles is responsible for the observed solubility enhancement.
- ASNPs demonstrate potential for sustained drug delivery, which may lead to reduced toxicity and improved therapeutic outcomes for atazanavir sulfate.
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