Thermally Conductive Excipient Expands KinetiSol® Processing Capabilities.

We report for the first time that incorporation of a thermally conductive excipient (TCE) modifies the thermal conductivity of the ternary drug-polymer-TCE compositions such that high-energy mixing can occur for prolonged periods at a selected steady-state temperature during the KinetiSol process. In this study, candurin, a TCE, is incorporated within a composition that is processed by high-energy mixing from the KinetiSol process to increase the thermal conductivity of the ternary composition. The improved thermal conductivity promotes heat transfer and enables the high-energy mixing applied during the KinetiSol process to be continued for prolonged time intervals at a selected steady-state temperature, instead of undergoing a continued increase in temperature when the TCE is not present in the composition. The addition of candurin does not impact the molecular structure and mixing of the drug and polymer in ASDs from solid-state NMR characterizations. Compositions with candurin achieved a steady-state processing temperature with + 5°C of the target temperature, and these compositions demonstrated the ability to mix for prolonged time periods while maintaining within this steady-state temperature range, thus enabling the formation of an ASD at a temperature that the drug does not chemically degrade. This study demonstrated that inclusion of the TCE modified the composition's thermal conductivity to efficiently dissipate heat to achieve a selected steady-state temperature during the KinetiSol process, thus providing prolonged mixing times at a lower temperature for dissolving the drug into the polymer to achieve an ASD without sacrificing product performance.

Personalized Medicine in Nasal Delivery: The Use of Patient-Specific Administration Parameters To Improve Nasal Drug Targeting Using 3D-Printed Nasal Replica Casts.

Effective targeting of nasal spray deposition could improve local, systemic, and CNS drug delivery; however, this has proven to be difficult due to the anatomical features of the nasal cavity, including the nasal valve and turbinate structures. Furthermore, nasal cavity geometries and dimensions vary between individuals based on differences in their age, gender, and ethnicity. The effect of patient-specific administration parameters was evaluated for their ability to overcome the barriers of targeted nasal drug delivery. The nasal spray deposition was evaluated in 10 3D-printed nasal cavity replicas developed based on the CT-scans of five pediatric and five adult subjects. Cromolyn sodium nasal solution, USP, modified with varying concentrations of hypromellose was utilized as a model nasal spray to evaluate the deposition pattern from formulations producing a variety of plume angles. A central composite design of experiments was implemented using the formulation with the narrowest plume angle to determine the patient-specific angle for targeting the turbinate region in each individual. The use of the patient-specific angle with this formulation significantly increased the turbinate deposition efficiency compared to that found for all subjects using an administration angle of 30°, around 90% compared to about 73%. Generally, we found turbinate deposition increased with decreases in the administration angle. Deposition to the upper regions of the replica was poor with any formulation or administration angle tested. Effective turbinate targeting of nasal sprays can be accomplished with the use of patient-specific administration parameters in individuals. Further research is required to see if these parameters can be device-controlled for patients and if other regions can be effectively targeted with other nasal devices.

Combination forceps fuse both safety and efficiency.

BACKGROUND: Instrumentation prevents needle stick injury. OBJECTIVE: To review forceps that insure safety and facilitate tissue-handling and knot-tying efficiency. METHOD: Medical literature reports were reviewed using Ovid. Commercially available instruments were qualitatively tested. RESULTS: Suture platforms securely hold suture needles and can be used during knot tying. A wide range of combination forceps have been invented and can be broadly categorized as either skin hook or toothed combination forceps. CONCLUSIONS: Combination forceps fuse both efficiency and safety. Skin hook forceps may eventually be the optimal combination instrument, but toothed combination forceps are recommended.