Development of Thermal Spray Processes for Depositing Coatings on Thermoplastics.

Thermoplastics combine high freedom of design with economical mass production. Metallic coatings on thermoplastics enable power and signal transmission, shield sensitive parts inside of housings and can reduce the temperature in critical areas by functioning as a heat sink. The most used technical thermoplastics are polyamides (PA), while the described use cases are often realized using Cu. Consequently, several studies tried to apply copper coatings on PA substrates via thermal spraying; so far, this combination is only feasible using an interlayer. In this study, a new approach to metallize thermoplastics via thermal spraying based on validated state-of-the-art predictions of the thermoplastics' material response at relevant temperatures and strain rates is presented. Using these predictions, high velocity wire-arc spraying was selected as coating process. Furthermore, the process parameters were adapted to realize a continuous coating while also roughening the substrate during coating deposition. The resulting Cu coating on PA6 had a sufficiently high coating adhesion for post-treatment by grinding. The adhesion is achieved by in situ roughening during the coating application. The results indicate that different process parameters for initial layer deposition and further coating buildup are required due to the low thermal stability of PA6.

New Generation Nebulizers.

Standard nebulizers are intended for general purpose use and typically are continuously operated jet or ultrasonic nebulizers. Evolutionary developments such as breath-enhanced and breath-triggered devices have improved delivery efficiency and ease of use, yet are still suitable for delivery of nebulized medications approved in this category. However, recent developments of vibrating membrane or mesh nebulizers have given rise to a significant increase in delivery efficiency requiring reformulation of former drug products or development of new formulations to match the enhanced delivery characteristics of these new devices. In addition, the electronic nature of the new devices enables tailoring to specific applications and patient groups, such as guiding or facilitating optimal breathing and improving adherence to the therapeutic regimen. Addressing these patient needs leads to new nebulization technologies being embedded in devices with fundamentally distinct functionality, modes of operation and patient interfaces. Therefore, new generation nebulizers can no longer be regarded as one category with fairly similar performance characteristics but must be clinically tested and approved as drug/device combinations together with the specific drug formulation, similar to the approval of pressurized metered-dose inhalers and dry powder inhalers. From a regulatory viewpoint, it is required that drug and device are associated with each other as combinations by clear, mutually conforming labels or, even more desirably, by distinct container-closure systems (closed system nebulizer).

How Cold Is Cold Enough? Refrigeration of the Next-Generation Impactor to Prevent Aerosol Undersizing.

Background: Heat transfer from impactor to aqueous aerosols causes underestimation of droplet size due to evaporation. Hence, pharmacopeia suggests cooling the impactor to 5°C, which is well below aerosol temperature. In this study, we assessed the droplet size at four different impactor temperatures under controlled ambient conditions to compare the compendial 5°C method with our in-house method, where the impactor is cooled to aerosol temperature. Materials and Methods: A single nebulizer/compressor unit was used throughout. It produced an aerosol at 17°C when operated at 50% RH and 23°C RT ambient conditions. Thirty-six experiments were conducted with saline, 9 each at impactor temperatures of 5°C, 10°C, 17°C, and 23°C. NaCl stage deposition was determined by conductometry, mass on stages by weighing. Moreover, a simulation was carried out to track aerosol temperature when entering the impactor. Results: Measuring at 23°C yields a significantly smaller mass median aerodynamic diameter (MMAD) than at 5°C-17°C. Despite elevated water condensation in the impactor at 5°C and 10°C, there was no increase in MMAD compared with 17°C. Instead, droplet size determination at 5°C led to significantly smaller values than at 17°C, probably due to distorted volumetric impactor flow rates at different impactor temperatures. Reevaluation of data with flow rates adjusted for impactor temperature (14.1 L/min at 5°C vs. 15.0 L/min at 23°C) led to indistinguishable results at 5°C-17°C. A computational fluid dynamics (CFD) simulation confirmed rapid cooling of the incoming air within the inlet and stage 1 and, with it, the systematic droplet undersizing due to reduced volumetric airflow using a cooled impactor. Conclusions: As long as the impactor temperature is at or below aerosol temperature, no effects on droplet size can be observed. Measuring at aerosol temperature yields the same results as at 5°C, but prevents condensation. However, cooling the impactor well below ambient temperature can cause a systematic error in the volumetric flow rate through the impactor if not corrected accordingly.

New advances in aerosolised drug delivery: vibrating membrane nebuliser technology.

Innovative nebuliser systems bear the potential to greatly improve and expand the administration of therapeutic aerosols for the treatment of respiratory diseases. Exploiting the technology of a microperforated vibrating membrane offers a close control of the droplet size that is being generated and targeted to reach the lower airways, with little oropharyngeal deposition, thereby reducing undesired side effects. The greatly improved efficiency of such devices, as exemplified by the eFlow nebuliser (PARI), provides further advantages for the patient. A high respirable fraction due to the precisely defined perforations, low residual losses and the high liquid output rate combine to produce a highly efficient and fast administration of inhaled medications. Portability, ease of handling and noiseless operation have a positive effect on patient compliance, control of the therapy by the physician and the therapy costs.

The customised electronic nebuliser: a new category of liquid aerosol drug delivery systems.

Inhalation of aerosols is the preferred route of administration of pharmaceutical compounds to the lungs when treating various respiratory diseases. Inhaled antibiotics, hormones, peptides and proteins are potential candidates for direct targeting to the site of action, thus minimising systemic absorption, dilution and undesired side effects, as much lower doses (as low as a fiftieth) are sufficient to achieve a similar therapeutic effect, compared with oral administration. A quick relief from the symptoms and a good tolerance are the main advantages of aerosol therapy. A new class of electronic delivery device is now starting to enter the market. The eFlow electronic nebuliser (PARI GmbH, Germany) provides improved portability and, in some instances, cuts treatment time to only a fraction of what has been experienced with current nebulised therapy. Drug formulations and the device can be mutually adapted and matched for optimal characteristics to meet the desired therapeutic target. Reformulation of known and proven compounds in a liquid format are commercially attractive as they present a relatively low development risk for potential drug candidates and, thus, have become a preferred pathway for the development of new inhalation products.

Topical drug delivery in chronic rhinosinusitis patients before and after sinus surgery using pulsating aerosols.

OBJECTIVES: Chronic rhinosinusitis (CRS) is a common chronic disease of the upper airways and has considerable impact on quality of life. Topical delivery of drugs to the paranasal sinuses is challenging, therefore the rate of surgery is high. This study investigates the delivery efficiency of a pulsating aerosol in comparison to a nasal pump spray to the sinuses and the nose in healthy volunteers and in CRS patients before and after sinus surgery. METHODS: (99m)Tc-DTPA pulsating aerosols were applied in eleven CRSsNP patients without nasal polyps before and after sinus surgery. In addition, pulsating aerosols were studied in comparison to nasal pump sprays in eleven healthy volunteers. Total nasal and frontal, maxillary and sphenoidal sinus aerosol deposition and lung penetration were assessed by anterior and lateral planar gamma camera imaging. RESULTS: In healthy volunteers nasal pump sprays resulted in 100% nasal, non-significant sinus and lung deposition, while pulsating aerosols resulted 61.3+/-8.6% nasal deposition and 38.7% exit the other nostril. 9.7+/-2.0 % of the nasal dose penetrated into maxillary and sphenoidal sinuses. In CRS patients, total nasal deposition was 56.7+/-13.3% and 46.7+/-12.7% before and after sinus surgery, respectively (p<0.01). Accordingly, maxillary and sphenoidal sinus deposition was 4.8+/-2.2% and 8.2+/-3.8% of the nasal dose (p<0.01). Neither in healthy volunteers nor in CRS patients there was significant dose in the frontal sinuses. CONCLUSION: In contrast to nasal pump sprays, pulsating aerosols can deliver significant doses into posterior nasal spaces and paranasal sinuses, providing alternative therapy options before and after sinus surgery. Patients with chronic lung diseases based on clearance dysfunction may also benefit from pulsating aerosols, since these diseases also manifest in the upper airways.