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At least 325 records · Page 18Linked to original sources
PubMed1995

An evaluation of the mechanisms of drug release from glyceride bases.

A series of dispersions containing theophylline in Gelucires 43/01, 54/02, 50/02, 50/13 and 55/18 was prepared and the physical structures studied using differential scanning calorimetry. The dissolution, erosion and swelling profiles of the drug dispersions were assessed. Gelucire 43/01 and 54/02 systems were found to release the drug by a simple diffusion mechanism, with no evidence for erosion or swelling being noted. Gelucire 55/18, however, showed a more complex mechanism involving both diffusion and erosion. On increasing the drug load within the matrices, the predominance of the erosion mechanism increased. Drug release from Gelucire 50/13 matrices took place principally by erosion, although the process was dominated by swelling and subsequent disintegration of the matrix, rather than simple dissolution of the base as was found for Gelucire 55/18. Gelucire 50/02 matrices also exhibited swelling, although drug release occurred predominantly via diffusion. The study, therefore, demonstrates that Gelucires may release incorporated drugs by a number of mechanisms depending on the chemical composition of the base.

Absorption↗
PubMed1995

An investigation into the effects of preparation conditions and storage on the rate of drug release from pharmaceutical glyceride bases.

The effects of preparation conditions on the release of theophylline from Gelucires 50/13 and 55/18 have been investigated. Samples were prepared by melting physical mixes under controlled conditions, followed by either slow or fast (ambient) cooling to the solid state. A rapid cooling rate was shown to result in a slower release rate for 2% w/w dispersions in Gelucire 55/18, with the slow- and fast-cooled systems resulting in drug release via a diffusion and a mixed diffusion/erosion mechanism, respectively. At higher drug loading (30% w/w), the cooling rate did not effect the release characteristics. The erosion of Gelucire 50/13 was found to be more rapid for slowly cooled samples. Viscosity measurements were used as a means of assessing the chemical stability of the Gelucires, with evidence being found for degradation of Gelucire 55/18 on storage following heat treatment, while Gelucire 50/13 appeared to be stable. The effects of storage on the dissolution profiles of ambiently cooled systems were studied, with drug release from both bases increasing on ageing for up to 180 days.

Chemistry, Pharmaceutical↗
PubMed1991

The effects of glyceride structure on absorption and metabolism.

The subtle effects of the stereochemistry of acyl glycerols are apparent from the cited studies. It is not adequate to simply measure the fatty acid composition of dietary lipids or chylomicrons generated from them. To understand the importance of stereospecific acyl glycerols, simplification of the systems is necessary because of the incredible diversity found among dietary triacylglycerols. By feeding simple analogues corresponding to major triacylglycerols found in oils and fats it should be possible to determine the absorption, uptake into the mucosa, resynthesis into chylomicrons, and the stereospecificity that remains. Hydrolysis and uptake of these defined chylomicron triacylglycerols into adipose tissue or muscle could be followed and stereospecificity again determined in depot fats. Finally, the composition of the remnants, particularly the core and surface, and of the bound apoproteins needs to be related to their plasma residence time, hepatic removal, and deposition in nonhepatic tissues such as spleen, bone marrow, and arterial intima. Since increased serum cholesterol and atherogenicity in animals have been related to different dietary fats, some of the effects noted here, that is the retention of certain kinds of remnants in plasma, may lead to increased serum cholesterol and atherogenesis. We must study the metabolism of a few key stereospecific triacylglycerols in more detail to increase our understanding of their effects on hypercholesterolemia and atherogenesis.

Animals↗
PubMed1988

Enteral, oral, and rectal absorption of ceftriaxone using glyceride enhancers.

In vivo models in rodents and primates were used to investigate ways of overcoming the poor oral and rectal absorption of ceftriaxone. The sodium salt of ceftriaxone at 20 mg/kg was formulated in C8-C10 chain length, mono- and diglyceride extracts of coconut oil (Capmul) and administered intraduodenally to adult rats. Peak plasma levels of 17-52 micrograms/ml and bioavailability averaging 38% were attained. Significant plasma levels (42-45 micrograms/ml) were also demonstrated in squirrel monkeys with doses of 20 mg/kg ceftriaxone formulated in Capmul and given by the enteral route. Enteric-coated capsules containing this formulation were also orally administered to squirrel monkeys and gave high plasma levels (10-31 micrograms/ml) between 1 and 6 h following dosing. In rectal absorption studies, ceftriaxone formulated in Capmul as a suspension gave peak blood levels of 62-84 micrograms/ml (average bioavailability 42%) in the rabbit. In the baboon, rectal administration of ceftriaxone formulated with Capmul in a Witepsol H15 suppository gave Cmax levels ranging from 9 to 48 micrograms/ml, depending on the dose of the antibiotic and the drug/enhancer ratio.

Administration, Oral↗