Improved pharmaceutical properties of ritonavir through co-crystallization approach with liquid-assisted grinding method

Abstract

Ritonavir is a BCS class II antiretroviral agent which shows poor aqueous solubility and low oral bioavailability. The cocrystallization approach was selected to overcome these problems and to improve the physicochemical and mechanical properties of Ritonavir. The novel pharmaceutical Ritonavir-L-tyrosine cocrystals (RTC at a molar ratio of 1:1) were synthesized using the liquid assisted grinding (LAG) method. The possibility of molecular interactions between drug and coformer were studied using Gold software version 5.2. The newly formed crystalline solid phase was characterized through Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier transform-infrared spectroscopy (FT-IR), Scanning electron microscopy (SEM), and Solid-State Nuclear magnetic resonance (SSNMR). The improved pharmaceutical properties were confirmed by solubility, dissolution, and powder compaction study. The prepared cocrystals exhibited an 11.24-fold increase in solubility and a 3.73-fold increase in % of drug release at 1 h compared to pure drug. Tabletability and compaction behavior of the pure drug and cocrystal with added excipients assessed. The tabletability profile of cocrystals showed enhanced tabletting performance as compared to pure drug. The stability studies revealed that cocrystals were stable for at least one month when stored at 40 °C/75 % RH and 25 °C/60 % RH conditions. The cocrystallization approach was found to be very promising and showed an overall improved performance of Ritonavir.

Keywords:

• Cocrystallization
• ritonavir
• tyrosine
• liquid-assisted grinding
• docking

Disclosure statement

The authors report no conflict of interest.