This study involves mathematical simulation model such as in vitro-in vivo correlation (IVIVC) development for various extended release formulations of nimesulide loaded hydroxypropylmethylcellulose (HPMC) microparticles (M1, M2 and M3 containing 1, 2, and 3 g HPMC, respectively and 1 g drug in each) having variable release characteristics. In vitro dissolution data of these formulations were correlated to their relevant in vivo absorption profiles followed by predictability worth analysis of these Level A IVIVC. Nimaran was used as control formulation to validate developed formulations and their respective models. The regression coefficients of IVIVC plots for M1, M2, M3 and Nimaran were 0.834 9, 0.831 2, 0.927 2 and 0.898 1, respectively. The internal prediction error for all formulations was within limits, i.e., < 10%. A good IVIVC was found for controlled release nimesulide loaded HPMC floating M3 microparticles. In other words, this mathematical simulation model is best fit for biowaiver studies which involves study parameters as those adopted for M3 because the value of its IVIVC regression coefficient is the closest to 1 as compared to M1 and M2.

This study involves mathematical simulation model such as in vitro-in vivo correlation (IVIVC) development for various extended release formulations of nimesulide loaded hydroxypropylmethylcellulose (HPMC) microparticles (M1, M2 and M3 containing 1, 2, and 3 g HPMC, respectively and 1 g drug in each) having variable release characteristics. In vitro dissolution data of these formulations were correlated to their relevant in vivo absorption profiles followed by predictability worth analysis of these Level A IVIVC. Nimaran was used as control formulation to validate developed formulations and their respective models. The regression coefficients of IVIVC plots for M1, M2, M3 and Nimaran were 0.834 9, 0.831 2, 0.927 2 and 0.898 1, respectively. The internal prediction error for all formulations was within limits, i.e., < 10%. A good IVIVC was found for controlled release nimesulide loaded HPMC floating M3 microparticles. In other words, this mathematical simulation model is best fit for biowaiver studies which involves study parameters as those adopted for M3 because the value of its IVIVC regression coefficient is the closest to 1 as compared to M1 and M2.
Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; pharmacokinetics ; Cross-Over Studies ; Cyclooxygenase 2 Inhibitors ; administration & dosage ; pharmacokinetics ; Delayed-Action Preparations ; Humans ; Hypromellose Derivatives ; Methylcellulose ; analogs & derivatives ; Microspheres ; Models, Chemical ; Sulfonamides ; administration & dosage ; pharmacokinetics

Objective: To assess the effectiveness and adverse drug reactions of all-oral regimens for patients with multidrug-resistant tuberculosis. Methods: This retrospective study was conducted at 10 Programmatic Management of Drug Resistant Tuberculosis sites in Punjab province of Pakistan. Patients receiving treatment for drug resistant tuberculosis from July 2019 to December 2020 with at least interim result i.e. 6th month culture conversion or final outcomes (cured, complete, lost to follow-up, failure, death) available, were included in the study. Data was extracted from electronic data management system. For the reporting and management of adverse drug events, active tuberculosis drug safety monitoring and management was implemented across all sites. All the data was analyzed using SPSS version 22. Results: Out of 947 drug resistant tuberculosis patients included in this study, 579 (68%) of the patients had final outcomes available. Of these, 384 (67.9%) successfully completed their treatment. Out of 368 (32%) patients who had their interim results available, all had their 6th month culture negative. Combining new medications was thought to result in serious adverse outcomes such as QT prolongation. However, this study did not record any severe adverse events among patients. Conclusions: All-oral regimens formulation guided by overall treatment effectiveness resulted in treatment outcomes comparable to those obtained with traditional injectable treatment.