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Oil-based drug delivery systems have been studied in different aspects. The present study proposes a new application for an oil-based delivery system, focusing on controlled release until the drug reaches the later part of the small intestine. Bulk surfactants and interfacial surfactants were added into the oil formulation to provide a better mechanistic understating of the lipolysis. Validation of the modified in vitro method shows the overall conversion from medium-chain triglyceride oil (MCT oil) to free fatty acids (FFA) of 100 ± 4% in five replicates. This fully converted level and high reproducibility are fundamental for the following investigations where any retarding effect can be distinguished from the experimental errors. The results show that viscosity and thermodynamic activity have limited retardation. Furthermore, the former may change the kinetics of lipolysis, while the latter changes the equilibrium level. The gel-forming retarder (ethylcellulose) displayed a strong effect. Whereas the lipolysis was significantly retarded (>50%) when the retarders altered the interfacial composition (poloxamer 407), degradable interfacial surfactants did not have the same effect. However, surface-active, lipolysis-resistant retarders with a high CMC did not show a retarding effect. [ABSTRACT FROM AUTHOR]

The addition of glycerol to protein solutions is often used to hinder the aggregation and denaturation of proteins. However, it is not a generalised practice against chemical degradation reactions. The chemical degradation of proteins, such as deamidation and isomerisation, is an important deteriorative mechanism that leads to a loss of functionality of pharmaceutical proteins. Here, the influence of glycerol on the chemical degradation of a protein and its correlation to glycerol-induced conformational changes is presented. The time-dependent chemical degradation of a pharmaceutical protein, GA-Z, in the absence and presence of glycerol was investigated in a stability study. The effect of glycerol on protein conformation and oligomerisation was characterised using asymmetric field-flow fractionation and small-angle neutron scattering in a wide glycerol concentration range of 0–90% v/v. The results from the stability study were connected to the observed glycerol-induced conformational changes in the protein. A correlation between protein conformation and the protective effect of glycerol against the degradation reactions deamidation, isomerisation, and hydrolysis was found. The study reveals that glycerol induces conformational changes of the protein, which favour a more compact and chemically stable state. It is also shown that the conformation can be changed by other system properties, e.g., protein concentration, leading to increased chemical stability. [ABSTRACT FROM AUTHOR]

The primary focus of this review is a discussion regarding in vitro media for colon release, but we also give a brief overview of colon delivery and the colon microbiota as a baseline for this discussion. The large intestine is colonized by a vast number of bacteria, approximately 1012 per gram of intestinal content. The microbial community in the colon is complex and there is still much that is unknown about its composition and the activity of the microbiome. However, it is evident that this complex microbiota will affect the release from oral formulations targeting the colon. This includes the release of active drug substances, food supplements, and live microorganisms, such as probiotic bacteria and bacteria used for microbiota transplantations. Currently, there are no standardized colon release media, but researchers employ in vitro models representing the colon ranging from reasonable simple systems with adjusted pH with or without key enzymes to the use of fecal samples. In this review, we present the pros and cons for different existing in vitro models. Furthermore, we summarize the current knowledge of the colonic microbiota composition which is of importance to the fermentation capacity of carbohydrates and suggest a strategy to choose bacteria for a new more standardized in vitro dissolution medium for the colon. [ABSTRACT FROM AUTHOR]