Ritonavir

Solid lipid nanoparticles (SLNs) have emerged as a remarkable nano-colloidal system for drug delivery. This research work aims at developing and optimizing the Ritonavir loaded solid lipid nanoparticles for targeted drug delivery by solvent emulsification-evaporation method. The produced solid lipoid Ritonavir nanoparticles were characterized for various physicochemical in terms of size, surface charge, % entrapment efficiency (EE) and in-vitro drug release studies. The entrapment efficiency (%) range of solid lipid nanoparticles (SLNs) is between 16.23% to 54.23% with polydispersity index (PDI) of 0.2. The mean size of particles was found between 189.6 to 271.4 nm. This indicates particles are in uniform distribution. The zeta potential was found in the range of -36.54 to -41.57 mV for prepared solid lipid nanoparticles. The most EE% was about 54.23% achieved in the presence of Polysorbate 20. It was found that addition of Polysorbate 20 in optimized concentration in the process led to increased entrapment efficiency and particle size when compared with Span 20.  In this study, we showed the SLNs have more encapsulating Ritonavir with optimized drug release.

The aim of present research work was to formulate gastro retentive floating tablets containing Ritonavir. The floating tablets of Ritonavir was formulated by direct compression technique using natural, semi-synthetic and synthetic polymers such as gellan gum, HPMC K4M, and carbopol 971p. Sodium bicarbonate was used as gas generating agent. FTIR studies revealed that there is no interaction between the drug and the polymers used in the formulation. Prepared Ritonavir tablets were evaluated by various quality parameters including weight variation, hardness, friability, drug content, tablet density, floating test, swelling index, in-vitro drug release and showed satisfactory results. Formulations F2, F5, F6 showed satisfactory drug release of 90.3%, 94.3%, and 97.7% respectively. The optimized batch F6  shows good results and extended drug release.

A simple, precise and stability-indicating HPLC method was developed and validated for the simultaneous estimation of anti-retroviral drugs Lopinavir and Ritonavir. The separation was achieved on AgilentC8, 150mm* 4.6 ,5µ  column with isocratic flow. The mobile phase at a flow rate of 1.5ml consisted of 0.05M Potassium Dihydrogen Orthophosphate buffer and Acetonitrile: MeOH in the ratio of (80:20).The ratio of buffer: organic is (45:55).The UV detection was carried  out at 210nm. The method was successfully validated in accordance to ICH guidelines. This method was then used to study the stability aspects of both the drugs when subjected to acidic, alkaline, thermal and photo degradation condition.

A new rapid, precise and sensitive reverse phase high performance liquid chromatographic (RP-HPLC) method has been developed and validated for the estimation of Atazanavir and Ritonavir simultaneously in combined dosage form. The two components Atazanavir and Ritonavir were well resolved on an isocratic method, C18 column, utilizing a mobile phase composition of acetonitrile: 0.02M ammonium acetate buffer (40:60), v/v, pH 4.0) at a flow rate of 1.0 mL/min with UV detection at 205 nm. The retention time of Atazanavir and Ritonavir were 2.8 min and 5.7 min respectively. The developed method was validated for specificity, linearity, precision, accuracy, limit of detection (LOD), limit of quantification (LOQ) and robustness as per ICH guidelines. Linearity for Atazanavir and Ritonavir were found in the range of 18.0-42.0 µg/ml and 5.0-14.0 µg/ml, respectively. The percentage recoveries for Atazanavir and Ritonavir ranged from 98.9-101.0 % and 98.2-100.1 %, respectively. The proposed method could be used for routine analysis of Atazanavir and Ritonavir in their combined dosage forms.

A simple, economic, accurate Absorption ratio method was developed for the simultaneous estimation of Atazanavir Sulphate and Ritonavir in bulk and tablet dosage form. 0.1M Hydrochloric acid was used as a diluent. 1% Sodium Lauryl Sulphate is used as surfactant to enhance solubility of drugs in 0.1M hydrochloric acid. The absorptions were observed at 262.8nm and 297nm which were selected based on overlap spectra of Atazanavir Sulphate and Ritonavir. The linearity range was found to be 10-20 mg/ml. The proposed method was validated. The reports was expressed that the proposed method was found to be simple, precise, accurate and rapid for the simultaneous estimation of Atazanavir Sulphate and Ritonavir in bulk and tablet dosage form using absorption ratio method. 

A simple and rapid liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay method has been developed and validated for simultaneous quantification of two protease inhibitors ritonavir and atazanavir in human plasma. Saquinavir was used as an internal standard. The analytes were extracted from human plasma samples by solid-phase extraction technique using a Orpheus C18 extraction cartridges. The reconstituted samples were chromatographed on a C18 column by using a 85:15 (v/v) mixture of methanol and 5mM ammonium acetate as the mobile phase at a flow rate of 0.9 mL/min. The calibration curves obtained were linear (r ³ 0.99) over the concentration range of 8.0-1600.0 ng/mL for ritonavir and 50.5-5995.2 ng/mL for atazanavir. The results of the intra- and inter-day precision and accuracy studies were well within the acceptable limits. A run time of 2.0 min for each sample made it possible to analyze more than 300 plasma samples per day. The proposed method was found to be applicable to clinical studies.

A reversed phase high-performance liquid chromatographic method was developed and validated for the quantitative determination of two antiviral drugs viz. lopinavir and ritonavir. Chromatography was carried out by gradient  technique on a reversed-phase C18 Column, Phenomenex (250 x 4.6 mm, 5 µ) with mobile phase mixture of Buffer: Acetonitrile (45:55 v/v) was used as a mobile phase and the pH was adjusted into 4.5 by using with O-phosphoric acid, at a flow rate of 1.2 ml/min. The UV range was detected at 240nm for lopinavir and ritonavir respectively. The different analytical performance parameters such as linearity, precision, accuracy, and specificity, limit of detection (LOD) and limit of quantification (LOQ) were determined according to International Conference on Harmonization ICH Q2B guidelines. The linearity of the calibration curves for each analyte in the desired concentration range is good (r2 >0.9). The recovery of the method was between 102.1% and 100.1% for lopinavir and ritonavir respectively. Hence the proposed method is highly sensitive, precise and accurate and it successfully applied for the reliable quantification of API content in the commercial formulations of lopinavir and ritonavir. Key words: Lopinavir, Ritonavir, UV spectrophotometry, RP-HPLC.