MUCO-DIS: a new AFM-based nanoscale dissolution technique.

Mucoadhesion-based drug delivery systems have recently gained interest because of their bio-adhesion capability, which results in enhanced residence time leading to prolonged duration of action with the mucosal surface, potentially improving compliance and convenience. Mucoadhesion testing of these formulations is widely reported; however, this is technically challenging due to the absence of any standard methods and difficulty in conducting mucoadhesion, formulation-mucosal surface interaction, mucosal surface topography and drug release in a single experiment. As these measurements are currently conducted separately, on replicate formulations, results can often be subjective and difficult to correlate. Hence, the aim of the present study was to develop a new AFM-based single-entity ex vivo muco-dissolution (MUCO-DIS) technique to simultaneously evaluate mucoadhesion force, 3D surface topography, polymer dissolution and drug release characteristics. To demonstrate the potential of the current technique, the interactions between model pectin microparticles containing metformin HCl and a range of gastrointestinal mucosal surfaces (gastric, small intestine, large intestine and buccal) were studied. This novel system has not only successfully determined the mucoadhesion force, polymer dissolution and drug release information but has also highlighted the difference in microparticle performance with different mucosal targets. The current work has highlighted the potential of this newly developed MUCO-DIS system and we believe this will be a valuable tool for characterising these popular pharmaceutical formulations. This technique could also provide an opportunity to other scientific fields to evaluate materials, substrate behaviour and their interactions in their hydrated state at nanoscale with real-time chemical and surface mapping

Use of Central Nervous System (CNS) Medicines in Aged Care Homes: A Systematic Review and Meta-Analysis

Background: Both old age and institutionalization in aged care homes come with a significant risk of developing several long-term mental and neurological disorders, but there has been no definitive meta-analysis of data from studies to determine the pooled estimate of central nervous system (CNS) medicines use in aged care homes. We conducted this systematic review to summarize the use of CNS drugs among aged care homes residents. Methods: MEDLINE, EMBASE, CINAHL, Scopus, and International Pharmaceutical Abstracts (IPA) databases were searched (between 1 January 2000 and 31 December 2018) to identify population-based studies that reported the use of CNS medicines in aged care homes. Pooled proportions (with 95% confidence interval), according to study location were calculated. Results: A total of 89 studies reported the use of CNS medicines use in aged care. The pooled estimate of CNS drugs use varied according to country (from 20.3% in Ireland to 49.0% in Belgium) and region (from 31.7% in North America to 42.5% in Scandinavia). The overall pooled estimate of psychotropic medicines use was highest in Europe (72.2%, 95% CI, 67.1–77.1%) and lowest in ANZ region (56.9%, 95% CI, 52.2–61.4%). The pooled estimate of benzodiazepines use varied widely from 18.9% in North America to 44.8% in Europe. The pooled estimate of antidepressants use from 47 studies was 38.3% (95% CI 35.1% to 41.6%) with highest proportion in North America (44.9%, 95% CI, 35.3–54.5%). Conclusion: The overall use of CNS drugs varied among countries, with studies from Australia-New Zealand reported the lowest use of CNS drugs. The criteria for prescribing CNS drugs in clinical practice should be evidence-based. The criteria should be used not to prohibit the use of the listed medications but to support the clinical judgement as well as patient safety

Plasticiser-free 3D printed hydrophilic matrices: Quantitative 3D surface texture, mechanical, swelling, erosion, drug release and pharmacokinetic studies

Hydroxypropyl methyl cellulose, HPMC, a hydrophilic polymer, is widely used for the development of extended release hydrophilic matrices and it is also considered as a good contender for the fabrication of 3D printing of matrix tablets. It is often combined with plasticisers to enable extrusion. The aim of the current project was to develop plasticizer-free 3D printed hydrophilic matrices using drug loaded filaments prepared via HME to achieve an in vitro (swelling, erosion and drug release) and in vivo (drug absorption) performance which is analogous to hydrophilic matrix tablets developed through conventional approaches. Additionally, the morphology of the printed tablets was studied using quantitative 3D surface texture studies and the porosity calculated. Filaments were produced successfully and used to produce matrix tablets with acceptable drug loading (95–105%), mechanical and surface texture properties regardless of the employed HPMC grade. The viscosity of HPMC had a discernible impact on the swelling, erosion, HPMC dissolution, drug release and pharmacokinetic findings. The highest viscosity grade (K100M) results in higher degree of swelling, decreased HPMC dissolution, low matrix erosion, decreased drug release and extended drug absorption profile. Overall, this study demonstrated that the drug loaded (glipizide) filaments and matrix tablets of medium to high viscosity grades of HPMC, without the aid of plasticisers, can be successfully prepared. Furthermore, the in vitro and in vivo studies have revealed the successful fabrication of extended release matrices

Electrically Tunable Lens (ETL)-Based Variable Focus Imaging System for Parametric Surface Texture Analysis of Materials

Electrically tunable lenses (ETLs) are those with the ability to alter their optical power in response to an electric signal. This feature allows such systems to not only image the areas of interest but also obtain spatial depth perception (depth of field, DOF). The aim of the present study was to develop an ETL-based imaging system for quantitative surface analysis. Firstly, the system was calibrated to achieve high depth resolution, warranting the accurate measurement of the depth and to account for and correct any influences from external factors on the ETL. This was completed using the Tenengrad operator which effectively identified the plane of best focus as demonstrated by the linear relationship between the control current applied to the ETL and the height at which the optical system focuses. The system was then employed to measure amplitude, spatial, hybrid, and volume surface texture parameters of a model material (pharmaceutical dosage form) which were validated against the parameters obtained using a previously validated surface texture analysis technique, optical profilometry. There were no statistically significant differences between the surface texture parameters measured by the techniques, highlighting the potential application of ETL-based imaging systems as an easily adaptable and low-cost alternative surface texture analysis technique to conventional microscopy techniques

In-situ 3D nanoscale advanced imaging algorithms with integrated chemical imaging for the characterisation of pharmaceuticals

The present study aimed to develop and validate an advanced image stitching algorithm integrated with chemical imaging at the nanometre scale. This was applied to track the swelling, erosion, drug release and changes in surface texture of a swelling-controlled release system. The technique involves the delivery and withdrawal of a liquid droplet from the surface of the tablet alongside capturing multiple images of tablet surface using white light profilometry. The recovered liquid was then subject to chemical analysis for the quantification of drug and HPMC. The multiple images acquired during drug release were stitched together using an algorithm developed to generate a full tablet surface. New methods for swelling analysis (regional point, area and multiple regional analysis techniques) were also successfully developed. The results exhibited the exceptional capability of this technique for providing quantitative information regarding swelling, erosion, drug release and surface topography, hence negating the need for separate investigations. Moreover, it can also be anticipated that this technique may have potential use in other fields where surface dissolution, erosion and swelling have significant impact