Solid self-microemulsifying drug delivery system of ritonavir

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Nanotechnology

Background:

• Ritonavir (RTV) is a water-insoluble HIV protease inhibitor (PI) used as a booster to enhance the bioavailability of other HIV PIs.
• Poor aqueous solubility of RTV limits its oral bioavailability.
• Solid Self-Microemulsifying Drug Delivery Systems (S-SMEDDS) offer a promising approach to improve the delivery of poorly soluble drugs.

Purpose of the Study:

• To enhance the dissolution rate and oral bioavailability of water-insoluble Ritonavir (RTV).
• To formulate and characterize a novel Solid Self-Microemulsifying Drug Delivery System (S-SMEDDS) for RTV delivery.

Main Methods:

• Formulation of Liquid Self-Microemulsifying Drug Delivery System (L-SMEDDS) by optimizing ratios of Imwitor 988 (oil), Cremophor EL/RH 40 (surfactant), and Capmul GMS K-50 (cosurfactant).
• Adsorption of optimized L-SMEDDS onto Neusilin US-2 via wet granulation to create S-SMEDDS.
• Characterization of microemulsion droplet size, in vitro dissolution, X-ray diffraction (XRD) for crystallinity, stability studies, and in vivo pharmacokinetic evaluation in Wistar rats.

Main Results:

• Optimized L-SMEDDS exhibited significantly improved RTV dissolution compared to pure RTV powder.
• The resultant microemulsion droplets of L-SMEDDS ranged from 16-22 nm and were pH-independent.
• XRD analysis confirmed the conversion of crystalline RTV to an amorphous form within the SMEDDS formulation.
• In vitro studies demonstrated stable and enhanced dissolution of RTV from the optimized S-SMEDDS.
• In vivo studies in rats showed that S-SMEDDS approximately doubled the maximum plasma concentration (Cmax) and area under the curve (AUC0-24h) compared to an aqueous suspension of RTV.

Conclusions:

• Successful formulation of RTV S-SMEDDS tablets using Neusilin-US2 as a carrier.
• The S-SMEDDS formulation significantly enhances RTV solubility and oral bioavailability.
• The developed S-SMEDDS represents a viable strategy for improving the therapeutic efficacy of poorly soluble drugs like Ritonavir.