Tekućinski antisolvent postupak taloženja za modifikaciju topljivosti bikalutamida

Liquid antisolvent process was explored as a solubility modulating tool. Bicalutamide, a poorly water soluble drug, was used as a candidate. Low aqueous solubility and poor dissolution of bicalutamide results into poor and variable bioavailability. Therefore, the objective of the present work was to modify the solubility of bicalutamide using the liquid antisolvent precipitation process. HPMC E5 and Poloxamer 407 were shortlisted as a hydrophilic polymer and surfactant, respectively, for the process. Process optimization was done with respect to the hydrophilic polymer, surfactant and drug loading concentration. The resultant microcrystals were characterized with various instrumental techniques for material characterization such as IR, DSC, SEM, XRD, particle size, specific surface area and dissolution kinetics.Tekućinski antisolvent postupak upotrijebljen je za moduliranje topljivosti bikalutamida. Zbog vrlo slabe topljivosti u vodi i sporog oslobađanja, bioraspoloživost bikalutamida je mala i varijabilna. Cilj rada je poboljšati topljivost bikalutamida koristeći antisolvent precipitaciju. Kao hidrofilni polimer korišten je HPMC E5, a kao surfaktant Poloxamer 407. Variranjem količine polimera, surfaktanta i lijeka proces je optimiran. Nastali mikrokristali analizirani su uobičajenim instrumentalnim tehnikama za karakterizaciju materijala kao što su IR, DSC, SEM, XRD, veličina čestica, specifična površina i brzina oslobađanja

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 (30 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

Utilisation of by-products from sunflower-based biodiesel production processes for the production of fermentation feedstock

By-products streams from a sunflower-based biodiesel plant were utilised for the production of fermentation media that can be used for the production of polyhydroxyalkanoates (PHA). Sunflower meal was utilised as substrate for the production of crude enzyme consortia through solid state fermentation (SSF) with the fungal strain Aspergillus oryzae. Fermented solids were subsequently mixed with unprocessed sunflower meal aiming at the production of a nutrient-rich fermentation feedstock. The highest free amino nitrogen (FAN) and inorganic phosphorus concentrations achieved were 1.5 g L-1 and 246 mg L-1, respectively, when an initial proteolytic activity of 6.4 U mL-1 was used. The FANconcentrationwas increased to 2.3 g L-1 when the initial proteolytic activity was increased to 16 U mL-1. Sunflower meal hydrolysates were mixed with crude glycerol to provide fermentationmedia that were evaluated for the production of poly(3-hydroxybutyrateco- 3-hydroxyvalerate) (P(3HB-co-3HV)) using Cupriavidus necator DSM545. The P(3HB-co-3HV) (9.9 g l-1) produced contained 3HB and 3HV units with 97 and 3 mol %, respectively. Integrating PHA production in existing 1st generation biodiesel production plants through valorisation of by-product streams could improve their sustainability