The Effect of Solvents and Drying Temperature on the Physicochemical Properties of Darunavir and Darunavir Ethanolate Substances

Introduction. Usage of aggressive conditions (solvents, high temperature, etc.) in a dosage form manufacturing can lead to a change in the properties of a pharmaceutical substance. Darunavir (D) amorphous and darunavir ethanolate (DE) crystalline both have poor solubility, ability to pseudopolymorphism and are sensitive to high temperatures.Aim. Study the effect of solvents and drying temperature on the physicochemical properties of D and DE substancesMaterials and methods. D (Mylan Laboratories Limited), DE (Mylan Laboratories Limited), D (reference standard) 99,9 % (MSN Pharmachem Private Limited). D and DE weighed quantity was suspended in one of the solvents via magnetic stirrer and was dried via universal oven. Powder X-ray diffraction of dried samples was carried out via automatic powder diffractometer. Using DSC thermal properties of the samples were studied. Crystalline samples were examined using IR spectroscopy. Identification of D and DE was performed by HPLC method.Results and discussion. This article summarizes study results of the investigation of various solvents and drying temperature influence on the physicochemical properties of D and DE are presented. The impact of solvent type and drying temperatures in physicochemical properties of the APIs was studied by X-ray powder diffraction, differential scanning calorimetry, IR spectroscopy and HPLC methods. It was shown, that solvent type and drying temperatures can result in the presence of crystalline D solvates or amorphous D.Conclusion. To obtain the final drug containing as an API amorphous D, which perform better dissolution, one of the enlisted solvents can be used: dichloromethane, chloroform and heptane. In such case the intermediate product drying should be performed at not exceeding the solvent boiling point temperatures. In case of ethanol, methanol, acetone and tetrahydrofuran drying phase can be performed at temperatures, that are higher than melting points of obtained pseudopolymorphs. For the utilization of DE as an API only ethanol usage is efficient and drying temperature should not exceed 73.4 °C.

ANALYTICAL METHOD DEVELOPMENT FOR THE ESTIMATION OF DARUNAVIR BY DIAZOTIZATION AND COUPLING BY VISIBLE SPECTROPHOTOMETRY

Objectives: This proposed work describes simple and extraction free visible methods for the estimation of darunavir ethanolate (DNV) in bulk and tablet formulations. The methodology involves diazotization of DNV with nitrous acid followed by coupling with chromotropic acid (CA) (Method A)/ Bratton Marshall Reagent (Method B)/α-naphthol (Method C) to form colored products.Methods: All the methods were developed using a PerkinElmer (LAMBDA 25) UV–Visible spectrophotometer interfaced with UV Win lab software and 1 cm quartz cells. Results: Spectrophotometrically, DNV is estimated at 520 nm, 544 nm, and 464 nm for the reddish-pink color produced by CA, dark violet color with NED, and dark-greenish yellow with α-naphthol, respectively. The linear relationship was observed between absorbance and the corresponding concentration of drug in the range of 100–350 μg/mL, 10–100 μg/mL, and 10–60 μg/mL for Methods A, B, and C, respectively.Conclusion: The colorimetric methods were extensively validated as per the ICH guidelines. The developed methods were proven to be more accurate and precise by the statistical analysis.