2 research outputs found
Preparation, Evaluation and Optimization of Multiparticulate System of Mebendazole for Colon Targeted Drug Delivery by Using Natural Polysaccharides
Purpose: A Multiparticulate
system of Mebendazole was developed for colon targeted drug delivery by using
natural polysaccharides like Chitosan and Sodium-alginate beads.
Methods: Chitosan
microspheres were formulated by using Emulsion crosslinking method using Glutaraldehyde
as crosslinking agent. Sodium-alginate beads were formulated by using Calcium
chloride as gelling agent. Optimization for Chitosan microspheres was carried
out by using 23 full factorial design. 32 full factorial
design was used for the optimization of Sodium-alginate beads. The formulated
batches were evaluated for percentage yield, particle size measurement, flow
properties, percent entrapment efficiency, Swelling studies. The formulations
were subjected to Stability studies and In-vitro release study (with and
without rat caecal content). Release kinetics data was subjected to different
dissolution models.
Results: The
formulated batches showed acceptable particle size range as well as excellent
flow properties. Entrapment efficiency for optimized batches of Chitosan
microspheres and sodium alginate beads was found to be 74.18% and 88.48%
respectively. In-vitro release of drug for the optimized batches was found to
be increased in presence of rat caecal content. The best-fit models were koresmeyer-peppas
for Chitosan microspheres and zero order for sodium-alginate beads.
Conclusion: Chitosan and
Sodium-alginate was used successfully for the formulation of Colon targeted
Multiparticulate system
Randomized Clinical Trial of High-Dose Rifampicin With or Without Levofloxacin Versus Standard of Care for Pediatric Tuberculous Meningitis: The TBM-KIDS Trial
Background. Pediatric tuberculous meningitis (TBM) commonly causes death or disability. In adults, high-dose rifampicin may reduce mortality. The role of fluoroquinolones remains unclear. There have been no antimicrobial treatment trials for pediatric TBM.
Methods. TBM-KIDS was a phase 2 open-label randomized trial among children with TBM in India and Malawi. Participants received isoniazid and pyrazinamide plus: (i) high-dose rifampicin (30Â mg/kg) and ethambutol (R30HZE, arm 1); (ii) high-dose rifampicin
and levofloxacin (R30HZL, arm 2); or (iii) standard-dose rifampicin and ethambutol (R15HZE, arm 3) for 8 weeks, followed by 10 months of standard treatment. Functional and neurocognitive outcomes were measured longitudinally using Modified Rankin Scale (MRS) and Mullen Scales of Early Learning (MSEL).
Results. Of 2487 children prescreened, 79 were screened and 37 enrolled. Median age was 72 months; 49%, 43%, and 8% had stage I, II, and III disease, respectively. Grade 3 or higher adverse events occurred in 58%, 55%, and 36% of children in arms 1, 2, and 3, with 1 death (arm 1) and 6 early treatment discontinuations (4 in arm 1, 1 each in arms 2 and 3). By week 8, all children recovered to MRS score of 0 or 1. Average MSEL scores were significantly better in arm 1 than arm 3 in fine motor, receptive language, and expressive language domains (P < .01).
Conclusions. In a pediatric TBM trial, functional outcomes were excellent overall. The trend toward higher frequency of adverse events but better neurocognitive outcomes in children receiving high-dose rifampicin requires confirmation in a larger trial.
Clinical Trials Registration. NCT02958709