Simulated gastro-intestinal digestion is widely employed in many fields of food and nutritional sciences, as conducting human trials are often costly, resource intensive, and ethically disputable. As a consequence, in vitro alternatives that determine endpoints such as the bioaccessibility of nutrients and non-nutrients or the digestibility of macronutrients (e.g. lipids, proteins and carbohydrates) are used for screening and building new hypotheses. Various digestion models have been proposed, often impeding the possibility to compare results across research teams. For example, a large variety of enzymes from different sources such as of porcine, rabbit or human origin have been used, differing in their activity and characterization. Differences in pH, mineral type, ionic strength and digestion time, which alter enzyme activity and other phenomena, may also considerably alter results. Other parameters such as the presence of phospholipids, individual enzymes such as gastric lipase and digestive emulsifiers vs. their mixtures (e.g. pancreatin and bile salts), and the ratio of food bolus to digestive fluids, have also been discussed at length. In the present consensus paper, within the COST Infogest network, we propose a general standardised and practical static digestion method based on physiologically relevant conditions that can be applied for various endpoints, which may be amended to accommodate further specific requirements. A frameset of parameters including the oral, gastric and small intestinal digestion are outlined and their relevance discussed in relation to available in vivo data and enzymes. This consensus paper will give a detailed protocol and a line-by-line, guidance, recommendations and justifications but also limitation of the proposed model. This harmonised static, in vitro digestion method for food should aid the production of more comparable data in the future.

https://hal.archives-ouvertes.fr/hal-01209876/document

A standardised static in vitro digestion method suitable for food – an international consensus

Liposomes have been considered promising and versatile drug vesicles. Compared with traditional drug delivery systems, liposomes exhibit better properties, including site-targeting, sustained or controlled release, protection of drugs from degradation and clearance, superior therapeutic effects, and lower toxic side effects. Given these merits, several liposomal drug products have been successfully approved and used in clinics over the last couple of decades. In this review, the liposomal drug products approved by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) are discussed. Based on the published approval package in the FDA and European public assessment report (EPAR) in EMA, the critical chemistry information and mature pharmaceutical technologies applied in the marketed liposomal products, including the lipid excipient, manufacturing methods, nanosizing technique, drug loading methods, as well as critical quality attributions (CQAs) of products, are introduced. Additionally, the current regulatory guidance and future perspectives related to liposomal products are summarized. This knowledge can be used for research and development of the liposomal drug candidates under various pipelines, including the laboratory bench, pilot plant, and commercial manufacturing.

https://www.mdpi.com/1420-3049/27/4/1372/pdf?version=1645180343

A Review of Liposomes as a Drug Delivery System: Current Status of Approved Products, Regulatory Environments, and Future Perspectives

Connected healthcare: Improving patient care using digital health technologies.

The approaches for enhancing oral bioavailability of biomacromolecules, such as peptides and proteins, including chemical modification, absorption enhancers, mucoadhesive systems, liposomes and nano-microparticles are comprehensively reviewed, and the status of these approaches and their relative merits analyzed, focusing on the status of nano-microparticles. Finally, it is pointed out that on the basis of nano-microparticles, analyzing and designing all aspects of drug release and absorption systematically and personally, oral drug delivery system of peptides and proteins for clinical applications is expected to construct.

Approaches for Enhancing Oral Bioavailability of Peptides and Proteins

Machine learning predicts 3D printing performance of over 900 drug delivery systems.

Machine learning directed drug formulation development.

Clofazimine is an anti-mycobacterial agent used as part of a multidrug treatment for leprosy. Recently clofazimine has shown promising activity against multidrug resistant tuberculosis. Clofazimine has been previously known to exist in two different crystal forms, or polymorphs, which are triclinic (F I) and monoclinic (F II) in crystal structure. The thermodynamic relationship between, and the solubility of, these different crystal structures of clofazimine has not previously been characterized. In this work, their solid and solution properties are studied, and as a result, two novel polymorphs of clofazimine (an orthorhombic crystal polymorph and a high temperature polymorph with a monoclinic structure) are reported. The properties of these new solid forms are compared and contrasted with those of the two previously reported polymorphs using thermal, spectroscopic, and microscopic techniques. Molecular modeling studies were also carried out to predict the relative thermodynamic relationship and the crys...

Investigation into the Solid and Solution Properties of Known and Novel Polymorphs of the Antimicrobial Molecule Clofazimine

Clofazimine is an antimycobacterial agent that is routinely used for the treatment of leprosy. Clofazimine has also been shown to have high clinical potential for the treatment of many Gram-positive pathogens, including those that exhibit high levels of antibiotic resistance in the medical community. The use of clofazimine against these pathogens has largely been limited by the inherently poor water solubility of the drug substance. In this work, the possibility of repurposing and reformulating clofazimine to maximize its clinical potential is investigated. To achieve this, the potential of novel salt forms of clofazimine as supersaturating drug-delivery vehicles to enhance the aqueous solubility and gastrointestinal solubility of the drug substance was explored. The solution properties of seven novel salt forms, identified during an initial screening process, were examined in water and in a gastrointestinal-like media and were compared and contrasted with those of the free base, clofazimine, and the comm...

Role of Biorelevant Dissolution Media in the Selection of Optimal Salt Forms of Oral Drugs: Maximizing the Gastrointestinal Solubility and in Vitro Activity of the Antimicrobial Molecule, Clofazimine

Turning down the heat: The case for mild hyperthermia and thermosensitive liposomes

Three novel solvates of sulfamethazine (SMT), an anti-microbial and anti-infective sulfonamide drug with the solvents – dimethylacetamide, dimethylformamide and dimethyl sulfoxide have been identified and characterized by analytical techniques including differential scanning calorimetry, thermogravimetric analysis, X-ray diffraction and Raman spectroscopy. All three are 1 : 1 solvates. Crystal structure analysis revealed N–H–O type intermolecular hydrogen bonding interactions between SMT and the solvent imparting stability to the solvate structure. Thermal analysis measurements for the stoichiometry of the solvates were in good agreement with the single crystal data. The solubility of the solvates in their respective solvents at 25 °C has been determined.

Pauric Bannigan

Papers

Machine learning directed drug formulation development.

Investigation into the Solid and Solution Properties of Known and Novel Polymorphs of the Antimicrobial Molecule Clofazimine

Role of Biorelevant Dissolution Media in the Selection of Optimal Salt Forms of Oral Drugs: Maximizing the Gastrointestinal Solubility and in Vitro Activity of the Antimicrobial Molecule, Clofazimine

Turning down the heat: The case for mild hyperthermia and thermosensitive liposomes

Study of three solvates of sulfamethazine