Oral liquids are often preferred for drug administration to patients for whom swallowing is difficult, however formulating modified release versions can be challenging. A potential route to achieve modified release in oral liquids is by using fluid (sheared) gels formed by introducing a shear field during gelation in gel-forming biopolymers. These fluid gels can act as pourable viscoelastic fluids but retain true gel micro/nano structure. Here, we have demonstrated that fluid gels have potential as paediatric oral liquids preventing release of ibuprofen in simulated gastric fluid. Subsequent release at pH 7.4 was affected by the duration of exposure and magnitude of acid pH with a linear relationship between onset of release and the preceding acidic exposure duration. Delayed release was a result of increasing gel stiffness, a consequence of the acidity of the initial release media and exposure time. A much faster release rate was measured when exposure time in acid was 10 min compared with 60 min. This study highlights the potential to design fluid gels that are tuned to have a specified stiffness at a particular pH and exposure time. This could enable the preparation oral liquids with modified release behaviour.
Direct mixing of alginate and divalent cations such as Ca 2+ generally produces heterogeneous gels that form almost instantaneously. Therefore, is particularly difficult to measure the rheological properties of this gelation event due to the rapid gelation kinetics. In this study, the gelation of alginate when exposed to a solution of CaCl 2 was measured by using a modified rheometer. This modification involved attaching a petri dish to the lower plate of the rheometer into which, filter paper impregnated with CaCl 2 solution was added. A semipermeable membrane was then placed above the filter paper as a barrier to prevent the filter paper imbibing the gel. Samples of 4%w/w alginate were loaded onto the semi-permeable membrane and measurements were taken using 55mm parallel plate geometry. Measurements of G′ and Gʺ were determined as a function of time to monitor gelation. Once gelation was complete the filter paper was removed and replaced with filter paper impregnated with calcium chelators (EDTA, sodium citrate) to assess the degradation of the gel. The results showed that this technique was suitable for analysing the external gelation of alginate with a sharp increase in G′ in the first three minutes which then plateaued over the remainder of the test. It was also shown that gel stiffness reduced to a greater extent on exposure to EDTA compared with sodium citrate. This method is not only suitable for measuring rapid gelation kinetics on exposure to cross-linkers, but has potential applications in modelling the in situ gelation behaviour in simulated physiological environments. Graphical AbstractHighlights: A novel method for the rheological measurements of the gelation of alginate from an external source of calcium ions Simple modification of a commercial rheometer Can be used to measure the degradation of alginate gel on exposure to calcium chelators Potential model for measurements of in situ gelation
Diclofenac topical formulations are often preferred for drug administration to patients who experience serious GIT problems. Absorption of the drug through the skin, however, can be challenging due to the natural protective feature of the stratum corneum (SC). In this article, fluid gels prepared from gellan gum were explored as a topical drug delivery vehicle.Rheological analysis of the formulations showed that it was possible to produce a topical gel with a viscosity and the mechanical strength similar to that of the commercially available
Co-administration of drugs with alcohol can affect the plasma concentration of drugs in patients. It is also known that the excipients used in the formulation of drugs may not always be resistant to alcohol. This study evaluates effect of varying alcohol concentrations on theophylline release from two grades of Grewia mollis polysaccharides. X-ray microtomography showed that native polysaccharide formulation compacts were not homogenous after the mixing process resulting in its failure in swelling studies. Removal of starch from the native polysaccharide resulted in homogenous formulation compacts resistant to damage in high alcoholic media in pH 6.8 (40%v/v absolute ethanol). Destarched polymer compacts had a significantly higher hardness (375N) than that of the native polysaccharide (82N) and HPMC K4M (146N). Dissolution studies showed similarity at all levels of alcohol tested (f=57-91) in simulated gastric media (pH 1.2). The dissolution profiles in the simulated intestinal fluids were also similar (f=60-94), with the exception of the native polysaccharide in pH 6.8 (40%v/v absolute ethanol) (f=43). This work highlights the properties of Grewia polysaccharide as a matrix former that can resist high alcoholic effects therefore; it may be suitable as an alternative to some of the commercially available matrix formers with wider applications for drug delivery as a cheaper alternative in the developing world.
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