Nanoseeded Desupersaturation and Dissolution Tests for Elucidating Supersaturation Maintenance in Amorphous Solid Dispersions.

The impact of residual drug crystals that are formed during the production and storage of amorphous solid dispersions (ASDs) has been studied using micron-sized seed crystals in solvent-shift (desupersaturation) and dissolution tests. This study examines the impacts of the seed size loading on the solution-mediated precipitation from griseofulvin ASDs. Nanoparticle crystals (nanoseeds) were used as a more realistic surrogate for residual crystals compared with conventional micron-sized seeds. ASDs of griseofulvin with Soluplus (Sol), Kollidon VA64 (VA64), and hydroxypropyl methyl cellulose (HPMC) were prepared by spray-drying. Nanoseeds produced by wet media milling were used in the dissolution and desupersaturation experiments. DLS, SEM, XRPD, and DSC were used for characterization. The results from the solvent-shift tests suggest that the drug nanoseeds led to a faster and higher extent of desupersaturation than the as-received micron-sized crystals and that the higher seed loading facilitated desupersaturation. Sol was the only effective nucleation inhibitor; the overall precipitation inhibition capability was ranked: Sol > HPMC > VA64. In the dissolution tests, only the Sol-based ASDs generated significant supersaturation, which decreased upon an increase in the nanoseed loading. This study has demonstrated the importance of using drug nanocrystals in lieu of conventional coarse crystals in desupersaturation and dissolution tests in ASD development.

Use of Bead Mixtures as a Novel Process Optimization Approach to Nanomilling of Drug Suspensions.

PURPOSE: We aimed to evaluate the feasibility of cross-linked polystyrene (CPS)-yttrium-stabilized zirconia (YSZ) bead mixtures as a novel optimization approach for fast, effective production of drug nanosuspensions during wet stirred media milling (WSMM). METHODS: Aqueous suspensions of 10% fenofibrate (FNB, drug), 7.5% HPC-L, and 0.05% SDS were wet-milled at 3000-4000 rpm and 35%-50% volumetric loading of CPS:YSZ bead mixtures (CPS:YSZ 0:1-1:0 v:v). Laser diffraction, SEM, viscometry, DSC, and XRPD were used for characterization. An nth-order model described the breakage kinetics, while a microhydrodynamic model allowed us to gain insights into the impact of bead materials. RESULTS: CPS beads achieved the lowest specific power consumption, whereas YSZ beads led to the fastest breakage. Breakage followed second-order kinetics. Optimum conditions were identified as 3000 rpm and 50% loading of 0.5:0.5 v/v CPS:YSZ mixture from energy-cycle time-heat dissipation perspectives. The microhydrodynamic model suggests that YSZ beads experienced more energetic/forceful collisions with smaller contact area as compared with CPS beads owing to the higher density-elastic modulus of the former. CONCLUSIONS: We demonstrated the feasibility of CPS-YSZ bead mixtures and rationalized its optimal use in WSMM through their modulation of breakage kinetics, energy utilization, and heat dissipation.

An observational study of patients' attitudes to tattoos and piercings on their physicians: the ART study.

INTRODUCTION: Perceptions regarding body art change over time as societal norms change. Previous research regarding patients' perceptions of physicians with exposed body art have been hampered by flaws in design methodology that incorporate biases into patient responses. This study was performed to determine whether emergency department (ED) patients perceived a difference in physician competence, professionalism, caring, approachability, trustworthiness and reliability in the setting of exposed body art. METHODS: Standardised surveys about physician competence, professionalism, caring, approachability, trustworthiness and reliability rating providers on a five point Likert scale were administered to patients in an ED after an encounter with a physician provider who demonstrated no body art modification, non-traditional piercings, tattoos, or both piercings and tattoos. Each provider served as their own control. Patients were blinded to the purpose of the survey. RESULTS: Patients did not perceive a difference in physician competence, professionalism, caring, approachability, trustworthiness or reliability in the setting of exposed body art. Patients assigned top box performance in all domains >75% of the time, regardless of physician appearance. CONCLUSION: In the clinical setting, having exposed body art does not significantly change patients' perception of the physician.