Dissolution profile of theophylline modified release tablets, using a biorelevant Dynamic Colon Model (DCM)

AbstractThe human proximal colon has been considered a favourable site to deliver drugs for local and systemic treatments. However, modified dosage forms face a complex and dynamically changing colonic environment. Therefore, it has been realized that in addition to the use of biorelevant media, the hydrodynamics also need to be reproduced to create a powerful in vitro dissolution model to enable in vivo performance of the dosage forms to be predicted.A novel biorelevant Dynamic Colon Model (DCM) has been developed which provides a realistic environment in terms of the architecture of the smooth muscle, the physical pressures and the motility patterns occurring in the proximal human colon. Measurements of pressure inside the DCM tube confirmed a direct association between the magnitude of the pressure signal with the occlusion rate of the membrane and the viscosity of the fluid.The dissolution profile and the distribution of the highly soluble drug, theophylline, were assessed by collecting samples at different locations along the DCM tube. Differences in the release rates of the drug were observed which were affected by the sampling point location, the viscosity of the fluid and the mixing within the DCM tube. Images of the overall convective motion of the fluid inside the DCM tube obtained using Positron Emission Tomography enabled relation of the distribution of the tracer to likely areas of high and low concentrations of the theophylline drug.This information provides improved understanding of how extensive phenomena such as supersaturation and precipitation of the drug may be during the passage of the dosage form through the proximal colon

Use of PLIF to assess the mixing performance of small volume USP 2 apparatus in shear thinning media

AbstractPlanar Laser Induced Fluorescence (PLIF) was used to assess mixing in small volume USP 2 dissolution apparatus for a range of viscous fluids which mimic gastrointestinal media, especially in the fed state. The release into the media from a specially prepared tablet containing Rhodamine 6G dye was tracked in time and the areal distribution method developed by Alberini et al. (2014a) was implemented to characterise the mixing performance. The distributions of the individual striations for selected mixing levels were also presented. These findings illustrate the poor mixing performance of the apparatus resulting in high variance of the dissolution data when working with viscous media. Analysis of data using CoV gives misleading results for the mixing performance of the small volume USP 2 dissolution apparatus. The results showed that the best mixing was mainly located above the blade and close to the wall, i.e. in the region where intensive motion takes place. This work presents important guidelines and precautions for choosing the proper sampling point for a wide range of liquid viscosities to minimize the variability of the dissolution data

Design of slurries for 3D printing of sodium-ion battery electrodes

Additive manufacturing of battery electrodes, using syringe deposition 3D printing or direct ink writing methods, enables intricate microstructural design. This process differs from traditional blade or slot-die coating methods, necessitating tailored physical properties of composite slurries to ensure successful deposition. Inadequately optimised slurries result in non-uniform extrusion, and challenges such as nozzle swelling or slumping, result in compromised structural integrity of the print, limiting the resolution. This study focuses on developing slurry design principles by thoroughly characterising the rheology of several water-based hard carbon anode slurry, both in shear and extension. Hard carbon is chosen as a material of significant importance for future sodium-ion batteries, and an example for this optimisation. The slurry composition is tailored to introduce yield stress by incorporating network-forming binder (carrageenan) and additive (carbon nanotubes), effectively reducing spreading, and preserving the printed coating's structure. Validation is performed through printing a large width line and evaluating spread. The same slurry is deposited on a smaller 150 μm nozzle, which introduces die swell and spreading effects. This offers insights for further optimization strategies. The strategies developed in this research for characterizing and optimizing the rheology through formulation lay the groundwork for the advancement of detailed 3D printed electrodes, contributing to the progress of additive manufacturing technologies in the field of battery manufacturing.</p

Modelling and simulation of the hydrodynamics and mixing profiles in the human proximal colon using Discrete Multiphysics

The proximal part of the colon offers opportunities to prolong the absorption window following oral administration of a drug. In this work, we used computer simulations to understand how the hydrodynamics in the proximal colon might affect the release from dosage forms designed to target the colon. For this purpose, we developed and compared three different models: a completely-filled colon, a partially-filled colon and a partially-filled colon with a gaseous phase present (gas-liquid model). The highest velocities of the liquid were found in the completely-filled model, which also shows the best mixing profile, defined by the distribution of tracking particles over time. No significant differences with regard to the mixing and velocity profiles were found between the partially-filled model and the gas-liquid model. The fastest transit time of an undissolved tablet was found in the completely-filled model. The velocities of the liquid in the gas-liquid model are slightly higher along the colon than in the partially-filled model. The filling level has an impact on the exsisting shear forces and shear rates, which are decisive factors in the development of new drugs and formulations

Influence of DC electric field upon the production of oil-in-water-in-oil double emulsions in upwards mm-scale channels at low electric field strength

AbstractA novel approach to create O/W/O is developed and described to achieve uniform oil drop size coated with thin layers of water. Drops were created using a test cell where the DC field is applied between different internal diameter (ID) needles (from which the O/W emulsion emits upwards into a continuous oil phase) and a grounded metal ring which was located at selected distances from the needle top. The advantages compared to the previous techniques consist of possibility of control on drop size and coating layer of the water using low electric field. A high speed imaging technique has been applied to determine drop size under different flow and electric field conditions. Without the electric field, several flow regimes were observed; stable formation of both the O/W/O emulsion and the O/W emulsion upstream of the cell was possible over a range of Reynolds numbers from 80 to 100. The effect of the electric field was found to be reverse below electric field strength of 60kVm−1, beyond this critical value there was significant impact upon the flow regime, drop size and emulsion structure. The impact of the electric field strength upon flow pattern and emulsion structure and a quantitative analysis of droplet size are presented. The work shows the results for the controlled creation of complex emulsion droplets combining electric field and mm scale channels. The differences with the other physical processes reported in the literature are discussed