Identification, Isolation, and Structural Characterization of Novel Forced Degradation Products of Darunavir Using Advanced Analytical Techniques Like UPLC-MS, Prep-HPLC, HRMS, NMR, and FT-IR Spectroscopy.

Since the stability of the pharmaceuticals plays a crucial role in efficacy and safety while using them in the treatment of disorders, the evaluation of purity and impurity profiling of pharmaceuticals is of utmost importance using efficient analytical techniques. The present study explains the identification, isolation, and characterization of stress degradation products of the anti-human immunovirus drug Darunavir. The degradation study was performed to evaluate the stability profile of Darunavir in different stress conditions like hydrolytic, oxidative, thermal, and photolytic conditions as per the ICH guidelines. Degradation products were identified using ultra-performance liquid chromatography coupled with mass spectrometry, isolated using semi-preparative high-performance liquid chromatography, and structural characterization by HRMS and 1H, 13C NMR (1D, 2D). Darunavir is relatively stable in oxidative, thermal, and photolytic conditions; however, considerable degradation was observed in acid and base hydrolysis. A total of five degradation products were identified and isolated in acid and base degradation. DP-1, DP -2, & DP-3 were observed in acid conditions, whereas in base conditions, along with DP-2, two more DPs, i.e., DP-4 & DP-5, were identified. Among the five DPs, two degradation products, namely DP-1: N-(4-(N-(3-amino-2-hydroxy-4-phenylbutyl)-N-isobutylsulfamoyl) phenyl) acetimidamide. & DP-3: hexahydrofuro[2,3-b]furan-3-yl(4-((4-acetimidamido-N-isobutylphenyl)sulfonamido)-3-hydroxy-1-phenylbutan-2-yl)carbamate, are novel, remaining degradation products DP-2: 4-amino-N-(3-amino-2-hydroxy-4-phenylbutyl)-N-isobutylbenzenesulfonamide, DP-4: 4-amino-N-(((5S)-4-benzyl-2-oxooxazolidin-5-yl) methyl) -N-isobutyl benzenesulfonamide and DP-5: methyl ((3S)-4-((4-amino-N-isobutylphenyl) sulfonamido)-3-hydroxy-1-phenylbutan-2-yl) carbamate are already reported tentatively using a single analytical technique coupled with mass analysis without any evidence from NMR and IR data. Hence, the present study focused on using High-Resolution Mass, 1D, and 2D 1H, 13C NMR data for concrete confirmation of structures for degradation products. Supplementary Information: The online version contains supplementary material available at 10.1007/s10337-022-04226-z.

Emerging Role of Biopharmaceutical Classification and Biopharmaceutical Drug Disposition System in Dosage form Development: A Systematic Review.

Biopharmaceutical classification system (BCS) is an advanced tool used for classifying medicines based on dissolution, water solubility, and intestinal permeability, which affect the absorption of active pharmaceutical ingredients (API) from immediate-release solid oral forms. It is useful to the formulation researchers to develop novel dosage forms based on modernistic rather than experimental approaches. The current review focuses on the fundamentals, objectives, guidance of BCS, characteristics of BCS drugs, their importance and applications of BCS. This review explains the challenges in drug development in terms of solubility and in vivo disposition. In the current review, new strategies for improving BCS II drug solubility as well as biopharmaceutical drug disposition properties which are utilized throughout the early stages of drug development and commercialization are mainly discussed.