Objective: For the measurement of lamivudine(LAM) and effavirenz (EVZ) in combination formulation, a uncomplicated and reliable liquid chromatographic approach has been proposed. Material and Method: Multivariate optimization of the RP-HPLC method, experimental conditions were accomplished using the design of experiments (DoE). The crucial method parameters were determined by a risk assessment. The mathematical models were created using three independent variables: percentage of acetonitrile, percentage of methanol, and buffer pH. The impacts of these independent elements were thoroughly investigated using the central composite design (CCD), which was utilized to analyze the response surface methodology. Result and Discussion: The LAM and EVZ retention time and resolution were both concurrently optimized using the desirability function. Acetonitrile, methanol, and phosphate buffer (pH 7.0) in the proportions of 40:20:40 v/v each were used in the optimized and anticipated data from the contour diagram, with detection occurring at a wavelength of 215 nm. Baseline separation of both pharmaceuticals with high resolution and a run time of under 6 minutes was accomplished under these ideal conditions. The validated test parameters followed ICH recommendations. As a consequence, the findings demonstrated that the Quality by Design methodology could be successfully used to optimize the RP-HPLC technique for the concurrent quantification of LAM and EVZ.

Integrating a Pharmacovigilance and Response Unit Team for a Better Adverse Drug Reaction Reporting and Management: Insights from a Prospective Cross-Sectional Study - Turkish Journal of Pharmaceutical Sciences

Objective: In this research, a validated RP-HPLC method for analyzing teriflunomide drug substance and its associated process-related impurities was developed with the assistance of the Quality by Design (QbD) approach. Material and Method: The QbD methodology employs statistical design of experiments to establish a robust method within a defined "design space." This design space outlines the experimental parameters' range within which alterations will not significantly impact the results. Chromatographic separation was done on HPLC system connected to a PDA detector, and the column used was the C18 YmC-Triart with specifications of 125 cm x 4.0 mm x 5.0 μm. The optimized mobile phase consisted of 0.5% triethylamine buffer with pH 4.0 (± 0.05) and acetonitrile in a 65:35 v/v ratio, flow rate of 1.0 ml/min. Detection wavelength of 210 nm. Result and Discussion: The developed RP-HPLC method successfully achieved high resolution, specificity, linearity, precision, accuracy, and robustness in quantifying both teriflunomide and its impurities simultaneously. Using a design of experiments (DoE) approach, critical method parameters were systematically identified and optimized, ensuring accurate and precise determination of impurity levels across the drug substance lifecycle. This validated method provides a thorough approach to ensuring the quality and safety of teriflunomide drug substances by delivering reliable data on impurity profiles. By applying Quality by Design (QbD) principles, not only does the method enhance understanding of the analytical process, but it also supports ongoing improvement and lifecycle management of the procedure.

Sertaconazole nitrate (SN), a broad-spectrum antifungal agent, is clinically employed against diverse dermatophyte infections. Its therapeutic efficacy, however, is constrained by poor aqueous solubility (0.006 mg/mL) and insufficient skin penetration from current commercial formulations. To address these limitations, this research focused on developing, optimizing (using a 3² factorial design), and assessing a topical nanovesicular gel incorporating sertaconazole nitrate-loaded ultraflexible liposomes (SN-UFLs) to enhance antifungal performance. The vesicles exhibited near-spherical morphology, with sizes ranging from 104.40 ± 1.20 to 151.90 ± 2.14 nm, zeta potential (ZP) values between −21.50 ± 1.25 and −51.20 ± 2.25 mV, and entrapment efficiency (EE) values from 77.60 ± 2.50% to 86.04 ± 3.20%. The optimized SN-UFL formulation (OPT-SN-UFL) was then integrated into a carbopol gel base. This SN-UFL-Gel was characterized for pH (6.5 ± 0.20), viscosity (499.66 ± 15 cP), spreadability (205 ± 1.50%), extrudability (154.18 ± 2.48 g/cm²), and drug content (96.7 ± 2.50%), as well as ex vivo skin permeation, skin irritation potential, and in vitro and in vivo antifungal efficacy. Compared with the marketed formulation, higher drug permeation and skin deposition were observed for SN-UFL-Gel. The SN-UFL-Gel exhibited a larger zone of inhibition (25 ± 1.50 mm) against Candida albicans compared to the commercially available formulation (20 ± 1.72 mm). The in vivo animal studies showed that SN-UFL-Gel showed better antifungal activity by efficient inhibition of infection induced in rats with Trichophyton mentagrophytes. The SN-UFL-Gel showed no signs of skin irritation and was stable at 4 ± 1, 25 ± 2, and 40 ± 2 °C for 3 months. Conclusively, the current work divulged successful augmentation of the overall effectiveness of sertaconazole nitrate by using deformable liposomes as a promising nanocarrier.