Ritonavir nanosuspensions prepared by microfluidization with enhanced solubility and desirable immunological...

Area of Science:

• Pharmaceutical Sciences
• Nanotechnology
• Drug Delivery

Background:

• Ritonavir (RTV) is an antiretroviral protease inhibitor with poor oral bioavailability.
• Developing effective oral formulations is crucial for improving RTV patient compliance and therapeutic outcomes.
• Nanosuspensions (NSs) offer a potential strategy to enhance the solubility and dissolution of poorly soluble drugs like RTV.

Purpose of the Study:

• To develop ritonavir (RTV) nanosuspensions (NSs) using a microfluidization technique.
• To characterize the physicochemical properties and dissolution profile of the RTV NSs.
• To evaluate the immunological impact of RTV NSs on lymphocyte sub-groups.

Main Methods:

• Microfluidization was employed for the preparation of RTV NSs.
• Particle size was determined using photon correlation spectroscopy.
• X-ray diffraction (XRD) and scanning electron microscopy (SEM) assessed particle crystallinity.
• Dissolution studies were conducted in fed state simulated intestinal fluid (FeSSIF).
• Flow cytometry analyzed lymphocyte sub-groups (CD4+/CD8+ ratio).

Main Results:

• RTV NSs were successfully prepared with particle sizes ranging from 400-500 nm.
• The crystalline properties of ritonavir remained unchanged during nanosuspension formation.
• Solubility of RTV NSs was enhanced approximately fivefold compared to coarse powder.
• Dissolution in FeSSIF showed 57% RTV release from NSs versus 18% from coarse powder.
• Immunological studies indicated no significant alteration in the CD4+/CD8+ ratio.

Conclusions:

• Microfluidization is an effective method for developing RTV NSs with improved physicochemical properties.
• The developed RTV NSs demonstrate significantly enhanced solubility and dissolution rates.
• RTV NSs appear safe from an immunological perspective, showing no adverse effects on CD4+/CD8+ ratios.
• Nanosuspension technology presents a viable approach for enhancing the oral administration of ritonavir.