Increase in the Specific Surface Area of Budesonide During Storage Postmicronization

Purpose. To evaluate an anomalous increase in the specific surface area of budesonide during storage postmicronization. Methods. Budesonide was micronized using a conventional air-jet mill. Surface areas and total pore volumes were measured using nitrogen sorption. Porosity was measured using mercury intrusion porosimetry. Particle size was measured using laser diffraction. Results. Budesonide exhibited a surface area increase of 22 ± 2% when stored at 25°C following micronization. The rate of surface area increase was lower at 20°C, suggesting a temperature-dependent stress relaxation mechanism for the micronized particles. The increase in surface area was accompanied by: (a) an increase in total pore volume; (b) a shift of the pore size distribution to smaller pore sizes; (c) a decrease in size of particles above 1 m; and (d) an increase in rugosity/surface roughness. Conclusions. Freshly micronized budesonide exhibited an unusual and significant postmicronization increase in specific surface area upon storage under ambient conditions. Postmicronization stress-relief by intraparticle crack formation, crack propagation with time, and particle fracture seems to be the primary mechanism behind this surface area increase.     

Efficacy and safety of tigecycline monotherapy compared with vancomycin plus aztreonam in patients with complicated skin and skin structure infections: Results from a phase 3, randomized, double-blind trial.

OBJECTIVES: To compare the effect of tigecycline monotherapy, a first-in-class, expanded broad spectrum glycylcycline, with the combination of vancomycin and aztreonam (V + A) in the treatment of complicated skin and skin structure infections (cSSSI). METHODS: A phase 3, double-blind study conducted in 8 countries enrolled adults with cSSSI who required intravenous (IV) antibiotic therapy for > or =5 days. Patients were randomly assigned (1:1) to receive either tigecycline or V + A for up to 14 days. Primary endpoint was the clinical cure rate at the test-of-cure visit. Secondary endpoints included microbiologic efficacy and in vitro susceptibility to tigecycline of bacteria that cause cSSSI. Safety was assessed by physical examination, laboratory analyses, and adverse event reporting. RESULTS: A total of 596 patients were screened for enrollment, 573 were analyzed for safety, 537 were included in the clinical modified intent-to-treat (c-mITT) population, 397 were clinically evaluable (CE), and 228 were microbiologically evaluable (ME). At test-of-cure, cure rates were similar between tigecycline and V + A groups in the CE population (82.9% versus 82.3%, respectively) and in the c-mITT population (75.5% versus 76.9%, respectively). Microbiologic eradication rates (subject level) at test-of-cure in the ME population were also similar between tigecycline and V + A. Frequency of adverse events was similar between groups, although patients receiving tigecycline had higher incidence of nausea, vomiting, dyspepsia, and anorexia, while increased ALT/SGPT, pruritis, and rash occurred significantly more often in V + A-treated patients. CONCLUSIONS: This study demonstrates that the efficacy of tigecycline monotherapy for the treatment of patients with cSSSI is statistically noninferior to the combination of V + A.