Advanced Electrohydrodynamic Atomisation Engineered Microneedle Coatings

Transdermal drug delivery (TDD) is an emerging field in the pharmaceutical remit compared to conventional methods (oral and parenteral). Microneedle (MN) based devices have gained significant interest as a strategy to overcome the skins formidable barrier; the stratum corneum and enhance drug delivery. The research presented here shows the successful coating of MNs with polymeric dye composites using Electrohydrodynamic atomisation (EHDA). Initially the rheological behaviours of polymeric solutions and morphological characterisation was carried out. This was followed by Quality by Design (QBD) implementation for the optimisation of the key process parameters in EHDA. Here, the electrosprayed nanoparticles and electrospun nano/micro fibres consisted of a polymeric matrix and dye. Eight formulations were assessed consisting of 5% w/v of polycaprolactone (PCL) in dichloromethane (DCM) and 5% w/v polyvinylpyrrolidone (PVP) in ethanol. A full factorial Design of Experiments (DoE) was used to assess the various parameters (applied voltage, deposition distance and flow rate). Further particle and fibre analysis was carried out using Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR), particle/fibre size distribution. In addition to this, in vitro release studies were carried out using fluorescein (FL) and rhodamine B (RhB) as model dyes and in vitro permeation studies were applied. From optimising EHDA more than 52% of particles were under 500 nm and fibres were in the micron range. In vitro drug release studies showed 100% drug release after 7 days for PCL particles and fibres. It also showed 100% drug release within 120 min for PVP particles and 300 minutes for PVP fibres. The release kinetics and the permeation study showed that the MN successfully pierced the membrane and the Es and Esp MN coatings released a large amount of the loaded drug within 6 hours for all formulations. This study has demonstrated the capability of these robust MNs to encapsulate a diverse range of drugs within a polymeric matrix giving rise to the potential of developing personalised medical devices

A review of emerging technologies enabling improved solid oral dosage form manufacturing and processing

Tablets are the most widely utilized solid oral dosage forms because of the advantages of self-administration, stability, ease of handling, transportation, and good patient compliance. Over time, extensive advances have been made in tableting technology. This review aims to provide an insight about the advances in tablet excipients, manufacturing, analytical techniques and deployment of Quality by Design (QbD). Various excipients offering novel functionalities such as solubility enhancement, super-disintegration, taste masking and drug release modifications have been developed. Furthermore, co-processed multifunctional ready-to-use excipients, particularly for tablet dosage forms, have benefitted manufacturing with shorter processing times. Advances in granulation methods, including moist, thermal adhesion, steam, melt, freeze, foam, reverse wet and pneumatic dry granulation, have been proposed to improve product and process performance. Furthermore, methods for particle engineering including hot melt extrusion, extrusion-spheronization, injection molding, spray drying / congealing, co-precipitation and nanotechnology-based approaches have been employed to produce robust tablet formulations. A wide range of tableting technologies including rapidly disintegrating, matrix, tablet-in-tablet, tablet-in-capsule, multilayer tablets and multiparticulate systems have been developed to achieve customized formulation performance. In addition to conventional invasive characterization methods, novel techniques based on laser, tomography, fluorescence, spectroscopy and acoustic approaches have been developed to assess the physical-mechanical attributes of tablet formulations in a non- or minimally invasive manner. Conventional UV-Visible spectroscopy method has been improved (e.g., fiber-optic probes and UV imaging-based approaches) to efficiently record the dissolution profile of tablet formulations. Numerous modifications in tableting presses have also been made to aid machine product changeover, cleaning, and enhance efficiency and productivity. Various process analytical technologies have been employed to track the formulation properties and critical process parameters. These advances will contribute to a strategy for robust tablet dosage forms with excellent performance attributes

Pseudoaneurysm of superficial femoral artery in a closed femur fracture - A case report

Background: Vascular injuries in simple close fractures are rare and low suspicion risk for primary surgeons. They include thrombus formation, hematomas, pseudoaneurysms, ischemic changes, and absent pulsations. These injuries can cause morbid sequelae, including compartment syndrome, reperfusion injury, exsanguination, and limb loss. Case presentation: Following a closed femoral shaft fracture, a 12-year-old boy came to us with a compromised superficial femoral artery (SFA). At the moment of fixing, there was no evidence of arterial involvement. He presented to the Out-patient Department (OPD) two weeks after the primary surgery with swelling at the fracture site. CT-Angiography was performed, and the swelling was diagnosed as a pseudoaneurysm of the superficial femoral artery, which was repaired using a Great Saphenous Vein (GSV) graft. Conclusion: These uncommon vascular injuries in closed fractures can be identified by a thorough clinical examination and specific diagnostic tests, and with prompt vascular repair, limb-threatening consequences are preventable. In a simple close femur fracture without suspicious signs in clinical findings, it's not a routine practice to check the vascular status by means of fancy and costly diagnostic tests

A rare case of tuberculous myocarditis: A diagnostic challenge in a tuberculosis‐endemic country

Key Clinical Message Tuberculous myocarditis is a rare presentation of tuberculosis, posing diagnostic challenges in endemic countries. Clinicians should consider this entity in patients with unexplained heart failure, conduction abnormalities, or sudden cardiac events in tuberculosis‐endemic regions. Abstract Tuberculous myocarditis is an uncommon manifestation of tuberculosis, often presenting as a diagnostic challenge, particularly in tuberculosis‐endemic regions. We report a case of a 58‐year‐old male with a history of chronic cough and fever, who presented with progressive dyspnea, generalized body swelling, and New York Heart Association (NYHA) Class IV heart failure. Clinical examination revealed signs of cardiac decompensation and congestive heart failure. Emergency echocardiography demonstrated biventricular dysfunction, and imaging showed clots in both atria and the left ventricle. The patient responded well to initial treatment with anticoagulants, antibiotics, diuretics, and inotropic support. Subsequent investigations, including computed tomography pulmonary angiogram (CTPA) and high‐resolution computed tomography (HRCT), confirmed active pulmonary tuberculosis. Anti‐tuberculous treatment (ATT) was initiated, and the patient showed remarkable improvement. The diagnosis of tuberculous myocarditis was based on clinical, radiological, and laboratory evidence, as cardiac biopsy was not performed due to resource limitations. Tuberculous myocarditis is an underreported condition, and clinicians should be vigilant about its occurrence, especially in tuberculosis‐endemic regions. Early recognition and prompt initiation of ATT can lead to favorable outcomes. This case highlights the importance of considering tuberculous myocarditis in patients with unexplained heart failure or cardiac abnormalities in areas with a high burden of tuberculosis

Electrospinning/electrospraying coatings for metal microneedles: a design of experiments (DOE) and quality by design (QbD) approach

The research presented here shows QbD implementation for the optimisation of the key process parameters in electrohydrodynamic atomisation (EHDA). Here, the electrosprayed nanoparticles and electrospun fibers consisting of a polymeric matrix and dye. Eight formulations were assessed consisting of 5% w/v of polycaprolactone (PCL) in dichloromethane (DCM) and 5% w/v polyvinylpyrrolidone (PVP) in ethanol. A full factorial DOE was used to assess the various parameters (applied voltage, deposition distance, flow rate). Further particle and fiber analysis using Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Fourier Transform Infrared Spectroscopy (FTIR), particle/fiber size distribution. In addition to this in vitro release studied were carried out using fluorescein and Rhodamine B as model dyes and in vitro permeation studies were applied. The results show a significant difference in the morphology of resultant structures as well as a more rapid release profile for the PVP particles and fibers in comparison to the sustained release profiles found with PCL. In vitro drug release studies showed 100% drug release after 7 days for PCL particles and showed 100% drug release within 120 min for PVP particles. The release kinetics and the permeation study showed that the MN successfully pierced the membrane and the electrospun MN coating released a large amount of the loaded drug within 6 h. This study has demonstrated the capability of these robust MNs to encapsulate a diverse range drugs within a polymeric matrix giving rise to the potential of developed personalised medical devices