Addressing drug–microbiome interactions: the role of healthcare professionals

Growing evidence has highlighted the potentially significant impact of drug–microbiome interactions on patient care. It is possible that hundreds of drugs alter the composition of the microbiome, including many drugs with non-microbial targets. Drug-induced alteration of the microbiome could increase patients’ risk of dysbiosis, a state of microbiome unbalance that increases the chance of disease. Further, a drug’s pharmacokinetics and pharmacodynamics can be altered by the microbiome via direct (e.g. biotransformation or bioaccumulation) and indirect processes. Although these interactions are potentially important for patient health and therapeutic success, they are rarely considered during drug development or in clinical practice. Healthcare professionals working across sectors should consider drug–microbiome interactions to improve patient outcomes. This review provides an overview of the current evidence relating to drug–microbiome interactions, and describes how healthcare professionals working in clinical settings, academia, policy and drug development can immediately begin to address drug–microbiome interactions as an integral part of their roles

In vivo evaluation of pH-sensitive polymeric microparticles for site specific drug delivery to the small intestine and colon

A novel emulsification/solvent evaporation process was developed to formulate prednisolone-loaded Eudragit L and S microparticles as drug delivery vehicles to target different regions of the gastrointestinal tract. Microparticles were characterised in vitro and in vivo. This is the first report of drug absorption form orally administered Eudragit L and S microparticles

An investigation into the digestibility of chitosan by human colonic bacteria.

The suitability of chitosan (non-crosslinked and crosslinked by glutaraldehyde) for colonic drug delivery was assessed by incubation of chitosan films in human faecal slurry and assessment of the film’s disappearance with time. It was found that non-crosslinked chitosan, was digested by colonic bacteria, but crosslinked chitosan was not

A New Method for Producing Pharmaceutical Co-crystals: Laser Irradiation of Powder Blends

In this work, a high-power CO2 laser was used to irradiate powder blends of co-crystal formers, with the specific aim of trying to cause recrystallization to a co-crystal structure. By varying the power and raster speed of the laser, it was found that sufficient thermal energy could be imparted to the powder to cause molecular rearrangement. It was possible to form co-crystals of caffeine with oxalic acid and caffeine with malonic acid. Interestingly, it was found that, to form co-crystals successfully, the coformers needed to sublime to an appreciable extent, which indicates that the mechanism of rearrangement involves interaction and nucleation in the vapor phase. Laser irradiation thus offers a new route to creation of pharmaceutical co-crystals and a potentially rapid screen for likely co-crystal formation between coforming pairs

The colon as a target for vaccination: quantification of lymphoid tissue in mouse colon prior to vaccination

Currently, most vaccines are given by injection. However, due to the inherent problems associated with injections, other routes of drug delivery are being researched, among them, the oral route. So far, research into oral vaccination has not differentiated between vaccine uptake by the different parts of the gastro-intestinal tract, such as the small and large intestine. It is likely that following oral vaccine administration, the vaccine is mostly taken up by the lymphoid tissue of the small intestine

Advanced machine-learning techniques in drug discovery

The popularity of machine learning (ML) across drug discovery continues to grow, yielding impressive results. As their use increases, so do their limitations become apparent. Such limitations include their need for big data, sparsity in data, and their lack of interpretability. It has also become apparent that the techniques are not truly autonomous, requiring retraining even post deployment. In this review, we detail the use of advanced techniques to circumvent these challenges, with examples drawn from drug discovery and allied disciplines. In addition, we present emerging techniques and their potential role in drug discovery. The techniques presented herein are anticipated to expand the applicability of ML in drug discovery

Laser irradiation to produce amorphous pharmaceuticals

Using a high-power CO2 laser to irradiate powder beds, it was possible to induce phase transformation to the amorphous state. Irradiation of a model drug, indometacin, resulted in formation of a glass. Varying the settings of the laser (power and raster speed) was shown to change the physicochemical properties of the glasses produced and all irradiated glasses were found to be more stable than a reference glass produced by melt-quenching. Irradiation of a powder blend of paracetamol and polyvinylpyrrolidone K30 was found to produce a solid amorphous dispersion. The results suggest that laser-irradiation might be a useful method for making amorphous pharmaceuticals