Exact solution of a one-dimensional Boltzmann equation for a granular tracer particle

We consider a one-dimensional system consisting of a granular tracer particle of mass $M$ in a bath of thermalized particles each of mass $m$. When the mass ratio, $M/m$, is equal to the coefficient of restitution, $\alpha$, the system maps to a a one-dimensional elastic gas. In this case, Boltzmann equation can be solved exactly. We also obtain expressions for the velocity autocorrelation function and the diffusion coefficient. Numerical simulations of the Boltzmann equation are performed for $M/m\neq \alpha$ where no analytical solution is available. It appears that the dynamical features remain qualitatively similar to those found in the exactly solvable case.Comment: 17 pages, 3 figures, Accepted in Physica

Breakdown of Energy Equipartition in a 2D Binary Vibrated Granular Gas

We report experiments on the equipartition of kinetic energy between grains made of two different materials in a mixture of grains vibrated in 2 dimensions. In general, the two types of grains do not attain the same granular temperature, Tg = 1/2m v^2. However, the ratio of the two temperatures is constant in the bulk of the system and independent of the vibration velocity. The ratio depends strongly on the ratio of mass densities of the grains, but is not sensitive to the inelasticity of grains. Also, this ratio is insensitive to compositional variables of the mixture such as the number fraction of each component and the total number density. We conclude that a single granular temperature, as traditionally defined, does not characterize a multi-component mixture.Comment: 4 pages, 5 figures, submitted to Physical Review Letters, updated reference

Thermalization of an anisotropic granular particle

We investigate the dynamics of a needle in a two-dimensional bath composed of thermalized point particles. Collisions between the needle and points are inelastic and characterized by a normal restitution coefficient $\alpha<1$. By using the Enskog-Boltzmann equation, we obtain analytical expressions for the translational and rotational granular temperatures of the needle and show that these are, in general, different from the bath temperature. The translational temperature always exceeds the rotational one, though the difference decreases with increasing moment of inertia. The predictions of the theory are in very good agreement with numerical simulations of the model.Comment: 7 pages, 6 Figures, submitted to PRE. Revised version (Fig1, Fig5 and Fig6 corrected + minor typos

Role of habit in treatment adherence among adults with cystic fibrosis

Among adults with cystic fibrosis (CF), medication adherence is low and reasons for low adherence are poorly understood. Our previous exploratory study showed that stronger 'habit' (ie, automatically experiencing an urge to use a nebuliser) was associated with higher nebuliser adherence. We performed a secondary analysis of pilot trial data (n=61) to replicate the earlier study and determine whether habit-adherence association exists in other cohorts of adults with CF. In this study, high adherers also reported stronger habit compared with low adherers. Habit may be a promising target for self-management interventions. ACtiF pilot, ISRCTN13076797. [Abstract copyright: © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

3D printing of tablets using inkjet with UV photoinitiation

Additive manufacturing (AM) offers significant potential benefits in the field of drug delivery and pharmaceutical/medical device manufacture. Of AM processes, 3D inkjet printing enables precise deposition of a formulation, whilst offering the potential for significant scale up or scale out as a manufacturing platform. This work hypothesizes that suitable solvent based ink formulations can be developed that allow the production of solid dosage forms that meet the standards required for pharmaceutical tablets, whilst offering a platform for flexible and personalised manufacture. We demonstrate this using piezo-activated inkjetting to 3D print ropinirole hydrochloride. The tablets produced consist of a cross-linked poly(ethylene glycol diacrylate) (PEGDA) hydrogel matrix containing the drug, photoinitiated in a low oxygen environment using an aqueous solution of Irgacure 2959. At a Ropinirole HCl loading of 0.41 mg, drug release from the tablet is shown to be Fickian. Raman and IR spectroscopy indicate a high degree of cross-linking and formation of an amorphous solid dispersion. This is the first publication of a UV inkjet 3D printed tablet. Consequently, this work opens the possibility for the translation of scalable, high precision and bespoke ink-jet based additive manufacturing to the pharmaceutical sector

Implementing the use of objective medication adherence data in routine clinical practice via the digital CFHealthHub platform: situation analysis and strategy development using the theoretical domains framework

Background Preventative inhaled treatments preserve lung function and reduce exacerbations in cystic fibrosis (CF). Self-reported adherence to these treatments is over-estimated. An online platform (CFHealthHub) has been developed with patients and clinicians to display real-time objective adherence data from dose-counting nebulisers, so that clinical teams can offer informed treatment support. Methods In this paper, we identify pre-implementation barriers to healthcare practitioners performing two key behaviours: accessing objective adherence data through the website CFHealthHub and discussing medication adherence with patients. We aimed to understand barriers during the pre-implementation phase, so that appropriate strategy could be developed for the scale up of implementing objective adherence data in 19 CF centres. Thirteen semi-structured interviews were conducted with healthcare practitioners working in three UK CF centres. Qualitative data were coded using the theoretical domains framework (TDF), which describes 14 validated domains to implementation behaviour change. Results Analysis indicated that an implementation strategy should address all 14 domains of the TDF to successfully support implementation. Participants did not report routines or habits for using objective adherence data in clinical care. Examples of salient barriers included skills, beliefs in consequences, and social influence and professional roles. The results also affirmed a requirement to address organisational barriers. Relevant behaviour change techniques were selected to develop implementation strategy modules using the behaviour change wheel approach to intervention development. Conclusions This paper demonstrates the value of applying the TDF at pre-implementation, to understand context and to support the development of a situationally relevant implementation strategy

When is forgetting not forgetting? A discursive analysis of differences in forgetting talk between adults with cystic fibrosis with different levels of adherence to nebulizer treatments

Forgetting is often cited as a reason why people struggle to adhere to treatments for chronic conditions. Interventions have tried to improve forgetting behavior using reminders. We used a discursive psychological approach to explore differences in how high and low adherers constructed forgetting their nebulizer treatments for cystic fibrosis. Interviews were conducted with 18 adults from a cystic fibrosis center in the United Kingdom. High adherers constructed forgetting treatments as occasional lapses in automaticity and temporary lapses in memory that they found easy to repair. Low adherers utilized forgetting to normalize more consistent nonadherence to treatments. However, it is important to contextualize forgetting as a discursive resource that helped these participants to negotiate moral discourses around adherence to treatment that reminder interventions cannot address; we therefore recommend a more behavioral, patient-focused, theory-driven approach to intervention development

Making tablets for delivery of poorly soluble drugs using photoinitiated 3D inkjet printing

© 2019 In this study, we investigate the viability of three-dimensional (3D) inkjet printing with UV curing to produce solid dosage forms containing a known poorly soluble drug, carvedilol. The formulation consists of 10 wt% carvedilol, Irgacure 2959, and a photocurable N-vinyl-2-pyrrolidone (NVP) and poly(ethylene glycol) diacrylate matrix, with the intention of forming an amorphous solid solution for release of carvedilol. Characterization of the printed tablets showed that the drug is an amorphous state and indicated hydrogen bonding interactions between the drug and cross-linked matrix. Several simple geometries (ring, mesh, cylinder, thin film) were printed, and the surface area to volume ratio of the prints was estimated. Over 80% carvedilol release was observed for all printed tablet geometries within ten hours. The release behaviour of carvedilol was fastest for the thin films, followed by the ring and mesh geometries, and slowest in the cylindrical forms. More rapid release was correlated to an increased surface area to volume ratio. This is the first study to implement 3D UV inkjet to make solid dispersion tablets suitable for poorly soluble drugs. Results also demonstrate that high drug-loaded tablets with a variety of release profiles can successfully be accessed with the same UV-curable inkjet formulation by varying the tablet geometry

3D extrusion printing of high drug loading immediate release paracetamol tablets

The manufacture of immediate release high drug loading paracetamol oral tablets was achieved using an extrusion based 3D printer from a premixed water based paste formulation. The 3D printed tablets demonstrate that a very high drug (paracetamol) loading formulation (80% w/w) can be printed as an acceptable tablet using a method suitable for personalisation and distributed manufacture. Paracetamol is an example of a drug whose physical form can present challenges to traditional powder compression tableting. Printing avoids these issues and facilitates the relatively high drug loading. The 3D printed tablets were evaluated for physical and mechanical properties including weight variation, friability, breaking force, disintegration time, and dimensions and were within acceptable range as defined by the international standards stated in the United States Pharmacopoeia (USP). X-Ray Powder Diffraction (XRPD) was used to identify the physical form of the active. Additionally, XRPD, Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) and differential scanning calorimetry (DSC) were used to assess possible drug-excipient interactions. The 3D printed tablets were evaluated for drug release using a USP dissolution testing type I apparatus. The tablets showed a profile characteristic of the immediate release profile as intended based upon the active/excipient ratio used with disintegration in less than 60 seconds and release of most of the drug within 5 minutes. The results demonstrate the capability of 3D extrusion based printing to produce acceptable high-drug loading tablets from approved materials that comply with current USP standards