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The objective of the research is to create a rapid, uncomplicated, accurate, and cost-effective RPHPLC technique for quantifying the quantities of Grazoprevir and Elbasvir concurrently in both pharmaceutical products and bulk materials. This approach has successfully accomplished the separation of Grazoprevir and Elbasvir in significant quantities. The separation was conducted with a Waters C18 (250 x 4.6 mm x 5 μ particle size) analytical column, with detection at a wavelength of 260 nm. The mobile phase included a blend of Methanol and Phosphate Buffer pH 4.0 at a volumetric ratio of 60:40. The separation was conducted using isocratic elution mode at a flow rate of 1.0 ml/min. Grazoprevir had a retention time of 2.400 minutes, whereas Elbasvir showed a retention length of 3.016 minutes. The quantification of Grazoprevir and Elbasvir was performed by utilizing PDA detection at a wavelength of 260 nm, employing a linear calibration curve. For accurate quantification, the concentration ranges of 20-100 μg/ml (with a correlation value of 0.9999) and 10-50 μg/ml (with a correlation coefficient of 0.999) were used. The suggested approach is well-suited for use in quality-control labs for the quantitative examination of medicines, both when employed separately or in combination, particularly in bulk quantities. This approach is distinguished by its effectiveness, while nevertheless guaranteeing a high degree of accuracy and precision. [ABSTRACT FROM AUTHOR]

Co-precipitation is an emerging manufacturing strategy for amorphous solid dispersions (ASDs). Herein, the interplay between processing conditions, surface composition, and release performance was evaluated using grazoprevir and hypromellose acetate succinate as the model drug and polymer, respectively. Co-precipitated amorphous dispersion (cPAD) particles were produced in the presence and absence of an additional polymer that was either dissolved or dispersed in the anti-solvent. This additional polymer in the anti-solvent was deposited on the surfaces of the cPAD particles during isolation and drying to create hierarchical particles, which we define here as a core ASD particle with an additional water soluble component that is coating the particle surfaces. The resultant hierarchical particles were characterized using X-ray powder diffraction, differential scanning calorimetry, scanning electron microscopy, and X-ray photoelectron spectroscopy (XPS). Release performance was evaluated using a two-stage dissolution test. XPS analysis revealed a trend whereby cPAD particles with a lower surface drug concentration showed improved release relative to particles with a higher surface drug concentration, for nominally similar drug loadings. This surface drug concentration could be impacted by whether the secondary polymer was dissolved in the anti-solvent or dispersed in the anti-solvent prior to isolating final dried hierarchical cPAD powders. Grazoprevir exposure in dogs was higher when the hierarchical cPAD was dosed, with ∼1.8 fold increase in AUC compared to the binary cPAD. These observations highlight the important interplay between processing conditions and ASD performance in the context of cPAD particles and illustrate a hierarchical particle design as a successful approach to alter ASD surface chemistry to improve dissolution performance. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: Untreated hepatitis C virus (HCV) infection can lead to cirrhosis, hepatocellular cancer, and even death and also increases liver diseases. The elbasvir/ grazoprevir (EBR-GZR) treatment regimen when given in HCV genotype (GT) 1 and GT4 infection for 8 or 12 weeks showed a high sustained virolgical response (SVR) rates in different populations. This study was assessed the effectiveness as well as safety of EBR-GZR in 12 week treatment regimen in HCV GT4-infected treatmentnaïve Saudi patients. Methods: This study conducted from June 2017 and December 2020 on Saudi HCV patients infected with GT4. Treatment protocol was given for 12 weeks in treatmentnaive HCV GT4 infected cirrhotic and non-cirrhotic participants which were later followed for a total of 24 weeks for safety and efficacy of EBR-GZR. Results: We analyzed data of 54 participants with HCV GT 4 infection. Mean age was (53.46 ± 14.94) Treatment regimen was given to 14 cirrhotic (F4) and 40 noncirrhotic (F0–F3). SVR was seen in 98.1% of participants with tolerable side effects and improved model for end stage liver disease (MELD) scores as fall in percentage seen from 18.5% to 14.8% in participants with MELD > 10. Conclusion: This retrospective study confirms that EBR-GZR for 12 weeks is a safe and effective treatment regimen in HCV GT4 patients in studied Saudi population. Treatment completion was followed by high SVR12 rates with improvement in prognostic markers of liver disease in participants with compensated cirrhosis. In short, the EBR-GZR combination showed efficacy in achieving the SVR12 in Child-Pugh B cirrhotic and non-cirrhotic population with a favorable safety profile. [ABSTRACT FROM AUTHOR]

The recommended treatment duration of hepatitis C virus (HCV) genotype 1a (GT1a) infection with elbasvir/grazoprevir (EBR/GZR) in the presence of a high baseline viral load and resistance associated substitutions (RAS) is 16 weeks with ribavirin added. The objective of this study was to evaluate the real-world effectiveness of 12 weeks of EBR/GZR without ribavirin and regardless of baseline viral load and RAS testing. This retrospective, observational cohort study was performed at five Norwegian hospitals that did not systematically utilize RAS testing. All adult patients with chronic HCV GT1a and compensated liver disease who had received 12 weeks of EBR/GZR without ribavirin and baseline RAS testing, were included. The primary endpoint was sustained virologic response at week 12 (SVR12), or if not available, at week 4 (SVR4). We included 433 patients and attained SVR data on 388. The mean age was 45.7 years (22–73 years). 67.2% were male. HIV co-infection was present in 3.8% (16/424) and cirrhosis in 4% (17/424). The viral load was >800 000 IU/mL in 55.0% (235/427) of patients. Overall SVR was achieved in 97.2% (377/388). SVR was achieved in 98.3% (169/172) of those with viral load ≤800 000 IU/mL and in 96.2% (202/210) of those with viral load >800 000 IU/mL. We observed high SVR rates among patients with HCV GT1a infection treated with EBR/GZR for 12 weeks without ribavirin, with no regard to baseline viral load and no RAS testing. [ABSTRACT FROM AUTHOR]