Characteristics, Complexation and Analytical Methods of Darunavir

Kogawa, Ana Carolina

doi:10.9734/bjpr/2014/7607

Cited by 5 publications

(2 citation statements)

References 19 publications

(40 reference statements)

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“…DRV is coadministered with food and low dose Ritonavir (RTV), a potent CYP3A4 inhibitor as a pharmacokinetic booster to result in clinically relevant increase in the systemic exposure (bioavailability increase by up to 40%) of DRV [ 5 , 6 ]. However, DRV suffer from disadvantages such as low solubility in water (0.15 mg/ml) and poor intestinal uptake due to drug efflux through active efflux transporter P-glycoprotein (P-gp) and by drug metabolism via Cytochrome P450 (CYP) 3A [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Role of P-Glycoprotein Inhibitors in the Bioavailability Enhancement of Solid Dispersion of Darunavir

Rehman

Nabi

Fazil

et al. 2017

BioMed Research International

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Objective The aim of the present study was to improve bioavailability of an important antiretroviral drug, Darunavir (DRV), which has low water solubility and poor intestinal absorption through solid dispersion (SD) approach incorporating polymer with P-glycoprotein inhibitory potential. Methods A statistical approach where design of experiment (DoE) was used to prepare SD of DRV with incorporation of P-glycoprotein inhibitors. Using DoE, different methods of preparation, like melt, solvent evaporation, and spray drying method, utilizing carriers like Kolliphor TPGS and Soluplus were evaluated. The optimized SD was characterized by DSC, FTIR, XRD, and SEM and further evaluated for enhancement in absorption using everted gut sac model, effect of food on absorption of DRV, and in vivo prospect. Results and Discussion DSC, FTIR, XRD, and SEM confirmed the amorphicity of drug in SD. Oral bioavailability studies revealed better absorption of DRV when given with food. Absorption studies and in vivo study findings demonstrated great potential of Kolliphor TPGS as P-glycoprotein inhibitor for increasing intestinal absorption and thus bioavailability of DRV. Conclusion It is concluded that SD of DRV with the incorporation of Kolliphor TPGS was potential and promising approach in increasing bioavailability of DRV as well as minimizing its extrusion via P-glycoprotein efflux transporters.

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Section: Introductionmentioning

confidence: 99%

Role of P-Glycoprotein Inhibitors in the Bioavailability Enhancement of Solid Dispersion of Darunavir

Rehman

Nabi

Fazil

et al. 2017

BioMed Research International

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“…Further, literature methods are available for estimation of individual Darunavir in bulk or formulation and impurity based literature method available by UPLC and MS compatible methods for formulation containing Darunavir. [8][9][10][11] Similarly, for Ritonavir, available literature methods are for impurity profiling of individual Ritonavir based product and its degradation impurities. 12,13 There were some literatures found for simultaneous estimation which include assay of multiple HIV drugs by single method and different fixed dose drug combination-based impurity method for HIV drugs like Atazanavir with Ritonavir, Lopinavir with Ritonavir.…”

Section: Introductionmentioning

confidence: 99%

Stability Indicating RP-UPLC Method for Impurity Profiling of Darunavir and Ritonavir in Fixed Dose Drug Combination Product

Buch,

Vaghani

2024

Ind. J. Pharm. Edu. Res

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Background:The goal of the proposed study was to develop and validate stability indicating mass compatible reverse phase UPLC method for impurity profiling of Darunavir Ethanolate and Ritonavir degradation impurities in fixed-dose drug combination products. Materials and Methods: The optimized chromatographic condition includes use of Zorbax Bonus C 18 column (150x2.1 mm, 1.8 µm) with mobile phase A (Buffer (55): Methanol ( 45)) and mobile phase B (Acetonitrile: (30) and Methanol ( 70)), flow rate of 0.22 mL/min and detection at 240 nm with gradient program of 50 min. The method was validated as per ICH quality guideline Q2 (R1) including specificity by forced degradation study to confirm suitability for intended use. Results: The observed retention time for Darunavir was 11.4 min and for Ritonavir was 30.0 min. The Limit of Quantitation (LOQ) for all degradation impurities found is 0.05%, equivalent to the reporting threshold level. The method was found linear and accurate in the range of LOQ to 150% with an observed range of % accuracy of 90.1 to 106.3 for all known impurities. The method was found precise based on less than 10.0% RSD and robust for deliberate changes. Considering the use of a volatile mobile phase, the method can be applied for LC-MS-based analysis for mass identification. Conclusion: The developed UPLC method was applied for impurity profiling during the release and stability study of Darunavir Ethanolate and Ritonavir in fixed-dose drug combination products.

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