In vitro digestion testing of lipid-based delivery systems: Calcium ions combine with fatty acids liberated from triglyceride rich lipid solutions to form soaps and reduce the solubilization capacity of colloidal digestion products

Devraj, Ravi; Williams, Hywel David; Warren, Dallas; Müllertz, Anette; Porter, Christopher John; Pouton, Colin W.

doi:10.1016/j.ijpharm.2012.11.024

Cited by 117 publications

(67 citation statements)

References 68 publications

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“…Elevation of pancreatin levels from 150 to 900 USPU/ml seems to influence the extent of total digestion for both LC-and MC-LBFs, with increases of 51 and 59% on average, respectively, whereas an elevation in calcium from 0 to 10 mM only results in increases of >19 and >31%, respectively. This is, however contrary to what previously has been reported by Zangenberg et al, where calcium was the most efficient promoter of in vitro digestion (6,29). If the Fig.…”

Section: In Vitro Lipolysis: Effect Of Varying Pancreatin and Calciumcontrasting

confidence: 72%

“…This is due to the more hydrophilic nature of the formulations, resulting in a decrease in solubilizing capacity of the LBF during dispersion by partitioning of the hydrophilic components of the LBFs into the aqueous phase (37). A general observation for the remaining six LBFs is that more drug is precipitating with increasing levels of calcium, which has been observed in previous publications as well (29). Calcium is known to precipitate as calcium soaps with FFAs, thereby removing some of the lipolysis product from the solution.…”

Section: In Vitro Lipolysis: Effect Of Varying Pancreatin and Calciummentioning

confidence: 55%

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Toward the Establishment of Standardized In Vitro Tests for Lipid-Based Formulations, Part 6: Effects of Varying Pancreatin and Calcium Levels

Sassene

Kleberg

Williams³

et al. 2014

AAPS J

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Abstract. The impact of pancreatin and calcium addition on a wide array of lipid-based formulations (LBFs) during in vitro lipolysis, with regard to digestion rates and distribution of the model drug danazol, was investigated. Pancreatin primarily affected the extent of digestion, leaving drug distribution somewhat unaffected. Calcium only affected the extent of digestion slightly but had a major influence on drug distribution, with more drug precipitating at higher calcium levels. This is likely to be caused by a combination of removal of lipolysis products from solution by the formation of calcium soaps and calcium precipitating with bile acids, events known to reduce the solubilizing capacity of LBFs dispersed in biorelevant media. Further, during the digestion of hydrophilic LBFs, like IIIA-LC, the un-ionizedionized ratio of free fatty acids (FFA) remained unchanged at physiological calcium levels. This makes the titration curves at pH 6.5 representable for digestion. However, caution should be taken when interpreting lipolysis curves of lipophilic LBFs, like I-LC, at pH 6.5, at physiological levels of calcium (1.4 mM); un-ionized-ionized ratio of FFA might change during digestion, rendering the lipolysis curve at pH 6.5 non-representable for the total digestion. The ratio of un-ionized-ionized FFAs can be maintained during digestion by applying non-physiological levels of calcium, resulting in a modified drug distribution with increased drug precipitation. However, as the main objective of the in vitro digestion model is to evaluate drug distribution, which is believed to have an impact on bioavailability in vivo, a physiological level (1.4 mM) of calcium is preferred.

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Section: In Vitro Lipolysis: Effect Of Varying Pancreatin and Calciumcontrasting

confidence: 72%

Section: In Vitro Lipolysis: Effect Of Varying Pancreatin and Calciummentioning

confidence: 55%

Toward the Establishment of Standardized In Vitro Tests for Lipid-Based Formulations, Part 6: Effects of Varying Pancreatin and Calcium Levels

Sassene

Kleberg

Williams³

et al. 2014

AAPS J

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“…Conversely, the digestion products of MCT-emulsions (medium chain FFAs) have a higher affinity for water and therefore rapidly move into the surrounding aqueous phase, thereby making the lipid surfaces easier to access by lipase. However, this effect tends to be more important when there are low levels of calcium present in the system, since calcium ions are known to form insoluble soaps with long chain FFAs that can also remove them from the droplet surfaces (Devraj et al, 2013). The fact that we did not observe a large difference between MCT-and LCT-emulsions suggests that the lipase was able to readily access the emulsified lipids in both types of system.…”

Section: Influence Of Oil Type On Lipid Digestionmentioning

confidence: 68%

Influence of lipid type on gastrointestinal fate of oil-in-water emulsions: In vitro digestion study

Zhang

et al. 2015

Food Research International

149

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The potential gastrointestinal fate of oil-in-water emulsions containing lipid phases from different sources was examined: vegetable oils (corn, olive, sunflower, and canola oil); marine oils (fish and krill oil); flavor oils (orange and lemon oil); and, medium chain triglycerides (MCT). The lowest rates and extents of lipid digestion were observed for emulsified flavor oil, followed by emulsified krill oil. There was no appreciable difference between the final amounts of free fatty acids released for emulsified digestible oils. Differences in the digestibility of emulsions prepared using different oils were attributed to differences in their compositions, e.g., fatty acid chain length and unsaturation. The particle size distribution, particle charge, microstructure, and macroscopic appearance of the emulsions during passage through the simulated GIT depended on oil type. The results of this study may facilitate the design of functional foods that control the digestion and absorption of triglycerides, as well as the bioaccessibility of hydrophobic bioactives.

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“…14,15 The fatty acids in SO have long chains and surface activity, which can form self-assembled nanomicelles together with bile salts in the body. [16][17][18][19][20] Our previous study found that the addition of SO improved biopharmaceutical properties and promoted the absorption of IT by self-assembled nanomicelles in vivo with sodium deoxycholate (DOC). 7 Therefore, in order to improve the bioavailability and the antiosteoporosis effects of CIT, SO was used to prepare CIT, and DOC was used to represent one of the main bile salts.…”

Section: Introductionmentioning

confidence: 99%

“…7 The properties of these fatty acids are similar to surfactants, which are helpful for the preparation of nanomicelles. [16][17][18][19][20] In the human body, the inherent bile acids or their salts have hydrophilic and hydrophobic surfaces, which are natural biosurfactants. Bile-acid salts can form nanomicelles with phospholipids, glycerides, fatty acids, and other surfactants as drug carriers, and promote drug absorption.…”

mentioning

confidence: 99%

Mechanism of enhanced antiosteoporosis effect of circinal–icaritin by self-assembled nanomicelles in vivo with suet oil and sodium deoxycholate

Jiang¹,

Li²,

Zhang³

et al. 2015

IJN

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Background Circinal–icaritin (CIT), one new active aglycone of Epimedium , can exert a beneficial effect on osteoporotic bone. However, its low bioavailability limits its clinical efficacy for the treatment of osteoporosis. Materials and methods In this paper, suet oil (SO) was used to improve the oral bioavailability of CIT and enhance its antiosteoporosis effect and absorption. After oral administration of CIT together with SO, the CIT and SO self-assembled into nanomicelles under the action of sodium deoxycholate (DOC) by bile secretion. The antiosteoporosis effects of the CIT-SO-DOC nanomicelles were evaluated in osteoporotic rats by bone mineral density, serum biochemical markers, bone microarchitecture, bone biomechanical properties, and related protein and gene expressions. We examined the bioavailability of CIT and its nanomicelles in vivo, and subsequently the nanomicelles were verified using transmission electron microscopy. Finally, we evaluated absorption across a rat intestinal perfusion model. Results Compared with CIT, in the CIT-SO groups, protein and messenger ribonucleic acid expressions of osteoprotegerin were increased, while expressions of receptor activator of nuclear factor-κB ligand in bone tissue were decreased; bone-turnover markers in serum of hydroxyproline, alkaline phosphatase, tartrate-resistant acid phosphatase 5b, and receptor activator of nuclear factor-κB ligand levels were decreased, while osteoprotegerin and osteocalcin levels were increased; and trabecular bone mass, microarchitecture, and bone biomechanical strength were enhanced. The relative bioavailabilities of CIT-SO high dosage, CIT-SO medium dosage, and CIT-SO low dosage (area under concentration–time curve [AUC] 0–∞ ) compared with that of raw CIT high dosage, CIT medium dosage, and CIT low dosage (AUC 0–∞ ) were 127%, 121%, and 134%, respectively. The average particle size of CIT-DOC was significantly decreased after adding SO ( P <0.01), and the intestinal permeability coefficients of CIT-SO-DOC nanomicelles in the duodenum, jejunum, ileum, and colon were all significantly improved ( P <0.01). Conclusion The increased antiosteoporosis effects and bioavailability of CIT-SO-DOC self-assembled nanomicelles were due to an increase in absorption of CIT by reducing the particle sizes of CIT. SO may be a practical oral carrier for antiosteoporosis drugs with low bioavailability.

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In vitro digestion testing of lipid-based delivery systems: Calcium ions combine with fatty acids liberated from triglyceride rich lipid solutions to form soaps and reduce the solubilization capacity of colloidal digestion products

Cited by 117 publications

References 68 publications

Toward the Establishment of Standardized In Vitro Tests for Lipid-Based Formulations, Part 6: Effects of Varying Pancreatin and Calcium Levels

Toward the Establishment of Standardized In Vitro Tests for Lipid-Based Formulations, Part 6: Effects of Varying Pancreatin and Calcium Levels

Influence of lipid type on gastrointestinal fate of oil-in-water emulsions: In vitro digestion study

Mechanism of enhanced antiosteoporosis effect of circinal–icaritin by self-assembled nanomicelles in vivo with suet oil and sodium deoxycholate

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In vitro digestion testing of lipid-based delivery systems: Calcium ions combine with fatty acids liberated from triglyceride rich lipid solutions to form soaps and reduce the solubilization capacity of colloidal digestion products

Cited by 117 publications

References 68 publications

Toward the Establishment of Standardized In Vitro Tests for Lipid-Based Formulations, Part 6: Effects of Varying Pancreatin and Calcium Levels

Toward the Establishment of Standardized In Vitro Tests for Lipid-Based Formulations, Part 6: Effects of Varying Pancreatin and Calcium Levels

Influence of lipid type on gastrointestinal fate of oil-in-water emulsions: In vitro digestion study

Mechanism of enhanced antiosteoporosis effect of&nbsp;circinal&ndash;icaritin by self-assembled nanomicelles&nbsp;in vivo with suet oil and sodium deoxycholate

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Mechanism of enhanced antiosteoporosis effect of circinal–icaritin by self-assembled nanomicelles in vivo with suet oil and sodium deoxycholate