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.

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.

Engineering and characterisation of BCG-loaded polymeric microneedles.

The aim of this study was to fabricate Bacillus Calmette-Guérin (BCG)-loaded microneedle patches using micromould casting technique and compare their efficacy with the injectable counterparts. The microneedle patches were formulated using sodium alginate (10% w/v) and trehalose (20% of polymer). The patches were characterised using optical microscopy, scanning electron microscopy and folding endurance. Serum IgG, TLC, granulocyte count, lymphocyte count and CRP were assessed and results were compared to that of intradermal injections alongside controls. The results showed that polymeric patches had a thickness of 0.8 mm, microneedle projections of 272 ± 12 µm and folding endurance of more than 300. Based on haematological and IgG ELISA assays, microneedle-based BCG administration significantly activated the immune cells and induced production of lymphocytes, granulocytes and peptide-specific IgG in immunised rats that were comparable to injectable counterparts. There was an increase in IgG antibodies from 3 g/L to 5.98 g/L and an increase in leucocytes from 2.6 × 109/L to 18.45 × 109/L. There was also an increase in granulocytes from 14.4% to 29.15% and lymphocyte count from 58.75% to 85.3%. It was concluded that BCG-coated polymeric microneedle patches are suitable for the transdermal delivery of vaccine without inducing discomfort usually observed with injections.

Improved transdermal delivery of cetirizine hydrochloride using polymeric microneedles.

PURPOSE: The aim of this study was to design and characterize microneedle patch formulation containing cetirizine hydrochloride. METHODS: Chitosan was co-formulated with cetirizine hydrochloride. Transdermal patches were prepared by casting this solution to microneedle molds. Control patches were formulated by casting this solution to a plain cuvet of same area as mold but lacking microneedles. An array of methods namely; differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and scanning electron microscopy (SEM) were employed for the characterization of the films and the microneedles accordingly whereas in vitro permeation studies were conducted across rat skin. Light microscopy was performed to assess any histological changes upon microneedles application onto the rat skin. RESULTS: The patches had a reproducible thickness (0.86 ± 0.06 mm) and folding endurance. Both the blank and drug loaded patches had 100 microneedles each of 300 micrometre length. In addition, the microneedle patches were ascribed with a two-fold increase in drug permeation across rat skin in the presence of microneedles as compared to the control formulations. Histological examination confirms a minimal invasion of the skin conferred by the microneedles. CONCLUSION: The microneedle patches serve as an alternate route of drug administration in patients with nausea and swelling difficulties. Graphical abstract Microneedle patch manifest a two-fold increase in the skin permeation of Cetirizine Hydrochloride as compared to the control that is drug loaded patch without microneedles.