Solubilisation of poorly water-soluble drugs during in vitro lipolysis of medium- and long-chain triacylglycerols

Christensen, Janne Ørskov; Schultz, Kirsten; Möllgaard, Birgitte; Kristensen, H. G.; Müllertz, Anette

doi:10.1016/j.ejps.2004.08.003

Cited by 175 publications

(89 citation statements)

References 31 publications

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“…Both I988 and I308 dispersed well in bile salt micelles. The digestion profiles for M812 (MCT) and soybean oil (LCT) from the current study show that the medium-chain triglycerides (MCT) was hydrolysed much faster than the long-chain triglycerides (LCT), which has been described previously in the literature (27). Almost 90 % of M812 was digested after 30 min time both under fed and fasted conditions.…”

Section: Effect Of Glycerides On the Fatty Acid Liberationmentioning

confidence: 65%

Design of Lipid-Based Formulations for Oral Administration of Poorly Water-Soluble Drug Fenofibrate: Effects of Digestion

Kazi

2012

AAPS PharmSciTech

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Abstract. Lipid-based drug carriers are likely to have influence on bioavailability through enhanced solubilization of the drug in the gastrointestinal tract. The study was designed to investigate the lipid formulation digestibility in the simulated gastro intestinal media. Fenofibrate was formulated in representative Type II, IIIA, IIIB and IV selfemulsifying/microemulsifying lipid delivery systems (SEDDS and SMEDDS designed for oral administration) using various medium-chain glyceride components, non-ionic surfactants and cosolvents as excipients. Soybean oil was used only as an example of long-chain triglycerides to compare the effects of formulation with their counterparts. The formulations were subjected to in vitro digestion specifically to predict the fate of the drug in the gastro intestinal tract after exposure of the formulation to pancreatic enzymes and bile. In vitro digestion experiments were carried out using a pH-stat maintained at pH 7.5 for 30 min using intestinal fluids simulating the fed and fasted states. The digestion rate was faster and almost completed in Type II and IIIA systems. Most of the surfactants used in the studies are digestible. However, the high concentration of surfactant and/or cosolvent used in Type IIIB or IV systems lowered the rate of digestion. The digestion of medium-chain triglycerides was faster than long-chain triglycerides, but kept comparatively less drug in the post digestion products. Medium-chain mixed glycerides are good solvents for fenofibrate as rapidly digested but to improve fenofibrate concentration in post digestion products the use of long-chain mixed glycerides are suggested for further investigations.KEY WORDS: fenofibrate; in vitro lipolysis; lipid formulation classification system; self-emulsifying/ microemulsifying drug delivery systems (SEDDS, SMEDDS).

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Section: Effect Of Glycerides On the Fatty Acid Liberationmentioning

confidence: 65%

Design of Lipid-Based Formulations for Oral Administration of Poorly Water-Soluble Drug Fenofibrate: Effects of Digestion

Kazi

2012

AAPS PharmSciTech

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“…The overconsumption of highly appealing energy dense foods is seen by some as a key contributor to this issue, and the consumption of diets rich in lipids is often cited as a leading cause of obesity (2). However, lipids are a good source of energy, essential fatty acids and play an important role in the absorption of micronutrients (vitamins, minerals), anti-nutrients (cholesterol) and class II pharmaceuticals (3)(4)(5)(6)(7)(8). What is unknown is how much the balance of the role of fat in our diet is evolutionary or environmental.…”

Section: Introductionmentioning

confidence: 99%

Impact of Protein Gel Porosity on the Digestion of Lipid Emulsions

Sarkar

Juan

Kolodziejczyk

et al. 2015

J. Agric. Food Chem.

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Abstract:The present study sought to understand how the structure of protein gels impacts lipolysis of gelled emulsions. The selected system consisted of an o/w emulsion embedded within gelatine gels. The gelatine gelled emulsions consisted of a discontinuous network of aggregated emulsion droplets, dispersed within a continuous network of gelatine. The rheology of the gelled emulsions was dominated by the rheological behaviour of the gelatine, at no point was yielding or brittle fracture observed suggesting a gelatine continuous structure rather than a bi-continuous gel. A direct relationship between the speed of fat digestion and gel average mesh size was found, indicating that the digestion of fat within gelatine gelled emulsions is controlled by the gels ability to slow lipase diffusion to the interface of fat droplets. Digestion of fat was facilitated by deposition of the gelatine network, which mainly occurred via surface erosion catalysed by proteases. Overall this work has demonstrated that protein gels can considerably slow the kinetics of lipolysis of gelled emulsions, key for the future development of structures to control fat digestion and or the delivery of nutrients to different parts of the gastrointestinal tract.Introduction:

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“…Unfortunately, information concerning the relationship between the degree of digestion and the drug release from SMEDDS is limited. Some researches demonstrated that the release of poorly water-soluble drugs from lipid-based formulations showed various performances under digestion: the dissolution rate might be improved, decreased, or unchanged compared with the undigested samples (20,21). These conflicting results indicate that the effect of lipolysis on the dissolution rate of lipidbased formulations depends on a certain drug-related parameters.…”

Section: Introductionmentioning

confidence: 89%

“…Meanwhile, the drug precipitation presented in the pellet phase could reduce the bioavailability (20,41,45). Some reports compared the drug contents in the aqueous phase of digested with undigested samples, and they found that the poorly water-soluble drugs showed various performances under digestion: the drug content might be improved (e.g., LU 28-179 and probucol), decreased (flupentixol), or unchanged (danazol) compared with the undigested samples (20,21,46). These conflicting results indicate that the effect of lipolysis on the drug dissolution rate from lipid-based formulations was depended on a certain drug-related parameters.…”

Section: Effect Of Lipolysis On Drug Release From Smedds With Differementioning

confidence: 99%

Effect of Lipolysis on Drug Release from Self-microemulsifying Drug Delivery Systems (SMEDDS) with Different Core/Shell Drug Location

Zhang

Zhao

et al. 2014

AAPS PharmSciTech

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Abstract. The objective of this study is to investigate the effect of lipolysis on the release of poorly watersoluble drug from SMEDDS in the perspective of drug core/shell location. For this purpose, four SMEDDS formulations with various core/shell properties were developed based on long-chain lipid or medium-chain lipid as well as different surfactant/oil ratios. Poorly water-soluble drugs, hymecromone and resveratrol, were significantly solubilized in all SMEDDS formulations and the diluted microemulsions. Fluorescence spectra analysis indicated that hymecromone was mainly located in the shell of microemulsions, while resveratrol was located in the core. The effect of lipolysis on the release rates of drugs with different core/shell locations were investigated by a modified in vitro drug release model. For the drug located in the shell, hymecromone, the release profiles were not affected during the lipolysis process and no significant differences were observed among four formulations. For the drug located in the core, resveratrol, the release rates were increased to various degrees depending on the extent of digestion. In conclusion, the drug core/shell location plays an important role for determining the effect of lipolysis on drug release from SMEDDS formulation.

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Solubilisation of poorly water-soluble drugs during in vitro lipolysis of medium- and long-chain triacylglycerols

Cited by 175 publications

References 31 publications

Design of Lipid-Based Formulations for Oral Administration of Poorly Water-Soluble Drug Fenofibrate: Effects of Digestion

Design of Lipid-Based Formulations for Oral Administration of Poorly Water-Soluble Drug Fenofibrate: Effects of Digestion

Impact of Protein Gel Porosity on the Digestion of Lipid Emulsions

Effect of Lipolysis on Drug Release from Self-microemulsifying Drug Delivery Systems (SMEDDS) with Different Core/Shell Drug Location

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