Age-mediated changes in the gastrointestinal tract

Physiological functions of the two extreme ends of the age spectrum, children (<18 y old) and older adults (aged 65 y and over), differ from healthy young adults. This consequently affects the pharmacokinetic profiles of administered drugs, which, in turn, impacts upon clinical practice and drug therapy. The gastrointestinal milieu acts as a distinct and vital organ regulating the dissolution, absorption and metabolism of orally ingested drugs. Age-mediated alteration in the physiology and function of the gut can reshape the pharmacokinetics of certain drugs. However, our understanding of this topic is limited. This article references the gut physiology of healthy adults to capture the available evidence in the literature on the extent and nature of the changes in childhood and older age. The gut, as an organ, is examined with regards to the effect of age on luminal fluid, microbiota, transit and motility, and the intestinal mucosa. Whilst drastic developmental changes were observed in certain aspects of the gastrointestinal environment, the examination reveals significant gaps in our knowledge in the physiology and function of the developing or ageing gut. The revelation of the unknown paves the way towards a better characterization of the human gastrointestinal tract for optimized drug therapy in children and older adults

To infinity and beyond: Strategies for fabricating medicines in outer space

Recent advancements in next generation spacecrafts have reignited public excitement over life beyond Earth. However, to safeguard the health and safety of humans in the hostile environment of space, innovation in pharmaceutical manufacturing and drug delivery deserves urgent attention. In this review/commentary, the current state of medicines provision in space is explored, accompanied by a forward look on the future of pharmaceutical manufacturing in outer space. The hazards associated with spaceflight, and their corresponding medical problems, are first briefly discussed. Subsequently, the infeasibility of present-day medicines provision systems for supporting deep space exploration is examined. The existing knowledge gaps on the altered clinical effects of medicines in space are evaluated, and suggestions are provided on how clinical trials in space might be conducted. An envisioned model of on-site production and delivery of medicines in space is proposed, referencing emerging technologies (e.g. Chemputing, synthetic biology, and 3D printing) being developed on Earth that may be adapted for extra-terrestrial use. This review concludes with a critical analysis on the regulatory considerations necessary to facilitate the adoption of these technologies and proposes a framework by which these may be enforced. In doing so, this commentary aims to instigate discussions on the pharmaceutical needs of deep space exploration, and strategies on how these may be met

Does sex matter? The influence of gender on gastrointestinal physiology and drug delivery.

We all respond differently to drugs. Personalised medicine aims to improve efficacy and reduce side effects, and efforts are being made to understand the physiological differences that underlie responses to drugs. Genetics, diet and disease state can be key; however, gender also plays an important role in pharmacokinetics, pharmacodynamics and drug toxicity. Differences in metabolism and clearance of drugs as a consequence of distinct hepatic and renal processes in males and females are now much better understood but little is known about gender differences in the gastrointestinal tract. As the recipient of all orally administered medications, differences at this level can have a major impact on drug delivery and bioavailability; yet these continue to be ignored and insufficiently studied in the context of drug disposition. The aim of this review is to highlight the known gender differences in gut physiology. Clinical case studies are presented, where possible, to illustrate the influence of these differences on drug disposition and gaps in current knowledge are highlighted to encourage further research in this area

Agronomic performance of five rice varieties and nutritive value of the straw from these varieties

Two separate experiments were conducted to assess the grain and straw yield (Exp. 1), chemical composition and in vitro gas production (Exp. 2) of five varieties of rice; Hybrid, Exbaika, Jasmine 85, IR841 and Long grain ordinary 2. Experiment 1 was conducted in a randomized complete block design with four replicates per variety. After harvesting, the rice straw from each variety was combined with Kapok leaf meal (KLM) at three inclusion levels (0, 25, 50%) to formulate a diet. The sole rice straw and formulated diets were analyzed for crude protein (CP), neutral detergent fiber (NDF), acid detergent fiber (ADF) and Ash. Approximately 0.2 g of each diet (sole and formulated) was incubated in a McDougall’s buffered rumen fluid under anaerobic condition for the in vitro gas production. The varieties differed (P &lt; 0.05) in relation to plant height, maturity days, percentage emergence, tiller number, straw yield and harvest index but did not differ in grain yield. The percentage emergence was in the range of 72.5 and 85.0%. with the highest (P = 0.003) recorded in the Hybrid variety. Plant height ranged from 90.5 to 110.8 cm with the highest (P = 0.046) reported in variety Long grain ordinary 2. Variety Long grain ordinary 2 had the longest (P&lt;0.001) mean maturity days with the least recorded in the Hybrid variety. The highest (P &lt; 0.05) straw yield was reported in variety Exbaika whilst Jasmine 85 had the least straw yield and harvest index. The CP concentration of the rice straw varieties increased numerically with an increase in the level of KLM. The NDF ranged from 622 g/kg DM to 913 g/kg DM for IR842 variety with 0% KLM and Long grain ordinary 2 variety with 25% KLM respectively. The ADF was in the range of 299.7 g/kg DM to 483.6 g/kg DM with the lowest reported in IR842 variety with 50% KLM. Mean asymptote gas production (b), fractional rate of gas production (c), in vitro gas production (IVGP) and in vitro organic matter digestibility (IVOMD) were not affected (P &lt;0.05) by the variety x KLM inclusion level interaction. However, IVGP at 24 h and IVOMD both differed (P &lt; 0.05) by variety. Varieties Jasmine 85, IR842 and Long grain ordinary 2 had higher IVGP and IVOMD as compared to the other two varieties. It was observed from the study that varieties IR841 and Long grain ordinary 2 provided higher grain and fodder production. The use of KLM as a replacement enhanced the nutrient composition, fermentation characteristics and digestibility

Innovations in Chewable Formulations: The Novelty and Applications of 3D Printing in Drug Product Design

Since their introduction, chewable dosage forms have gained traction due to their ability to facilitate swallowing, especially in paediatric, geriatric and dysphagia patients. Their benefits stretch beyond human use to also include veterinary applications, improving administration and palatability in different animal species. Despite their advantages, current chewable formulations do not account for individualised dosing and palatability preferences. In light of this, three-dimensional (3D) printing, and in particular the semi-solid extrusion technology, has been suggested as a novel manufacturing method for producing customised chewable dosage forms. This advanced approach offers flexibility for selecting patient-specific doses, excipients, and organoleptic properties, which are critical for ensuring efficacy, safety and adherence to the treatment. This review provides an overview of the latest advancements in chewable dosage forms for human and veterinary use, highlighting the motivations behind their use and covering formulation considerations, as well as regulatory aspects

Advancing non-destructive analysis of 3D printed medicines

Pharmaceutical 3D printing (3DP) has attracted significant interest over the past decade for its ability to produce personalised medicines on demand. However, current quality control (QC) requirements for traditional large-scale pharmaceutical manufacturing are irreconcilable with the production offered by 3DP. The US Food and Drug Administration (FDA) and the UK Medicines and Healthcare Products Regulatory Agency (MHRA) have recently published documents supporting the implementation of 3DP for point-of-care (PoC) manufacturing along with regulatory hurdles. The importance of process analytical technology (PAT) and non-destructive analytical tools in translating pharmaceutical 3DP has experienced a surge in recognition. This review seeks to highlight the most recent research on non-destructive pharmaceutical 3DP analysis, while also proposing plausible QC systems that complement the pharmaceutical 3DP workflow. In closing, outstanding challenges in integrating these analytical tools into pharmaceutical 3DP workflows are discussed

Virtually Possible: Enhancing Quality Control of 3D-Printed Medicines with Machine Vision Trained on Photorealistic Images

Three-dimensional (3D) printing is an advanced pharmaceutical manufacturing technology, and concerted efforts are underway to establish its applicability to various industries. However, for any technology to achieve widespread adoption, robustness and reliability are critical factors. Machine vision (MV), a subset of artificial intelligence (AI), has emerged as a powerful tool to replace human inspection with unprecedented speed and accuracy. Previous studies have demonstrated the potential of MV in pharmaceutical processes. However, training models using real images proves to be both costly and time consuming. In this study, we present an alternative approach, where synthetic images were used to train models to classify the quality of dosage forms. We generated 200 photorealistic virtual images that replicated 3D-printed dosage forms, where seven machine learning techniques (MLTs) were used to perform image classification. By exploring various MV pipelines, including image resizing and transformation, we achieved remarkable classification accuracies of 80.8%, 74.3%, and 75.5% for capsules, tablets, and films, respectively, for classifying stereolithography (SLA)-printed dosage forms. Additionally, we subjected the MLTs to rigorous stress tests, evaluating their scalability to classify over 3000 images and their ability to handle irrelevant images, where accuracies of 66.5% (capsules), 72.0% (tablets), and 70.9% (films) were obtained. Moreover, model confidence was also measured, and Brier scores ranged from 0.20 to 0.40. Our results demonstrate promising proof of concept that virtual images exhibit great potential for image classification of SLA-printed dosage forms. By using photorealistic virtual images, which are faster and cheaper to generate, we pave the way for accelerated, reliable, and sustainable AI model development to enhance the quality control of 3D-printed medicines

Colonic drug delivery: Formulating the next generation of colon-targeted therapeutics

Colonic drug delivery can facilitate access to unique therapeutic targets and has the potential to enhance drug bioavailability whilst reducing off-target effects. Delivering drugs to the colon requires considered formulation development, as both oral and rectal dosage forms can encounter challenges if the colon's distinct physiological environment is not appreciated. As the therapeutic opportunities surrounding colonic drug delivery multiply, the success of novel pharmaceuticals lies in their design. This review provides a modern insight into the key parameters determining the effective design and development of colon-targeted medicines. Influential physiological features governing the release, dissolution, stability, and absorption of drugs in the colon are first discussed, followed by an overview of the most reliable colon-targeted formulation strategies. Finally, the most appropriate in vitro, in vivo, and in silico preclinical investigations are presented, with the goal of inspiring strategic development of new colon-targeted therapeutics

3D Printed Tablets (Printlets) with Braille and Moon Patterns for Visually Impaired Patients

Visual impairment and blindness affects 285 million people worldwide, resulting in a high public health burden. This study reports, for the first time, the use of three-dimensional (3D) printing to create orally disintegrating printlets (ODPs) suited for patients with visual impairment. Printlets were designed with Braille and Moon patterns on their surface, enabling patients to identify medications when taken out of their original packaging. Printlets with different shapes were fabricated to offer additional information, such as the medication indication or its dosing regimen. Despite the presence of the patterns, the printlets retained their original mechanical properties and dissolution characteristics, wherein all the printlets disintegrated within ~5 s, avoiding the need for water and facilitating self-administration of medications. Moreover, the readability of the printlets was verified by a blind person. Overall, this novel and practical approach should reduce medication errors and improve medication adherence in patients with visual impairmentThe authors thank the Engineering and Physical Sciences Research Council (EPSRC), UK, for their financial support (EP/L01646X)S

A decrease in iron availability to human gut microbiome reduces the growth of potentially pathogenic gut bacteria: an in vitro colonic fermentation study

Iron-supplements are widely consumed; however most of the iron is not absorbed and enters the colon where potentially pathogenic bacteria can utilise it for growth. This study investigated the effect of iron availability on human gut microbial composition and function using an in vitro colonic fermentation model inoculated with faecal microbiota from healthy adult donors, as well as examining the effect of iron on the growth of individual gut bacteria. Batch fermenters were seeded with fresh faecal material and supplemented with the iron chelator, bathophenanthroline disulphonic acid (BPDS). Samples were analysed at regular intervals to assess impact on the gut bacterial communities. The growth of Escherichia coli and Salmonella Typhimurium was significantly impaired when cultured independently in iron-deficient media. In contrast, depletion of iron did not affect the growth of the beneficial species, Lactobacillus rhamnosus, when cultured independently. Analysis of the microbiome composition via 16S-based metataxonomics indicated that under conditions of iron chelation, the relative abundance decreased for several taxa, including a 10% decrease in Escherichia and a 15% decrease in Bifidobacterium. Metabolomics analysis using 1 HNMR indicated that the production of SCFAs was reduced under iron-limited conditions. These results support previous studies demonstrating the essentiality of iron for microbial growth and metabolism, but, in addition, they indicate that iron chelation changes the gut microbiota profile and influences human gut microbial homeostasis through both compositional and functional changes