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

Ravi Devraj; Hywel D Williams; Dallas B Warren; Anette Mullertz; Christopher J H Porter; Colin W Pouton

doi:10.1016/j.ijpharm.2012.11.024

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

Ravi Devraj, Hywel D Williams, Dallas B Warren, Anette Mullertz, Christopher J H Porter, Colin W Pouton

84 Citationer (Scopus)

Abstract

In vitro digestion testing is of practical importance to predict the fate of drugs administered in lipid-based delivery systems. Calcium ions are often added to digestion media to increase the extent of digestion of long-chain triglycerides (LCTs), but the effects they have on phase behaviour of the products of digestion, and consequent drug solubilization, are not well understood. This study investigates the effect of calcium and bile salt concentrations on the rate and extent of in vitro digestion of soybean oil, as well as the solubilizing capacity of the digestion products for two poorly water-soluble drugs, fenofibrate and danazol. In the presence of higher concentrations of calcium ions, the solubilization capacities of the digests were reduced for both drugs. This effect is attributed to the formation of insoluble calcium soaps, visible as precipitates during the digestions. This reduces the availability of liberated fatty acids to form mixed micelles and vesicles, thereby reducing drug solubilization. The use of high calcium concentrations does indeed force in vitro digestion of LCTs but may overestimate the extent of drug precipitation that occurs within the intestinal lumen.

Originalsprog	Engelsk
Tidsskrift	International Journal of Pharmaceutics
Vol/bind	441
Udgave nummer	1-2
Sider (fra-til)	323-333
ISSN	0378-5173
DOI	https://doi.org/10.1016/j.ijpharm.2012.11.024
Status	Udgivet - 30 jan. 2013

Emneord

Det tidligere Farmaceutiske Fakultet

Adgang til dokumentet

10.1016/j.ijpharm.2012.11.024

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Citationsformater

Devraj, R., Williams, H. D., Warren, D. B., Mullertz, A., Porter, C. J. H., & Pouton, C. W. (2013). 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. International Journal of Pharmaceutics, 441(1-2), 323-333. https://doi.org/10.1016/j.ijpharm.2012.11.024

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 D; Warren, Dallas B et al.
I: International Journal of Pharmaceutics, Bind 441, Nr. 1-2, 30.01.2013, s. 323-333.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Devraj, R, Williams, HD, Warren, DB, Mullertz, A, Porter, CJH & Pouton, CW 2013, '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', International Journal of Pharmaceutics, bind 441, nr. 1-2, s. 323-333. https://doi.org/10.1016/j.ijpharm.2012.11.024

Devraj R, Williams HD, Warren DB, Mullertz A, Porter CJH, Pouton CW. 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. International Journal of Pharmaceutics. 2013 jan. 30;441(1-2):323-333. doi: 10.1016/j.ijpharm.2012.11.024

Devraj, Ravi ; Williams, Hywel D ; Warren, Dallas B et al. / 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. I: International Journal of Pharmaceutics. 2013 ; Bind 441, Nr. 1-2. s. 323-333.

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abstract = "In vitro digestion testing is of practical importance to predict the fate of drugs administered in lipid-based delivery systems. Calcium ions are often added to digestion media to increase the extent of digestion of long-chain triglycerides (LCTs), but the effects they have on phase behaviour of the products of digestion, and consequent drug solubilization, are not well understood. This study investigates the effect of calcium and bile salt concentrations on the rate and extent of in vitro digestion of soybean oil, as well as the solubilizing capacity of the digestion products for two poorly water-soluble drugs, fenofibrate and danazol. In the presence of higher concentrations of calcium ions, the solubilization capacities of the digests were reduced for both drugs. This effect is attributed to the formation of insoluble calcium soaps, visible as precipitates during the digestions. This reduces the availability of liberated fatty acids to form mixed micelles and vesicles, thereby reducing drug solubilization. The use of high calcium concentrations does indeed force in vitro digestion of LCTs but may overestimate the extent of drug precipitation that occurs within the intestinal lumen.",

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AB - In vitro digestion testing is of practical importance to predict the fate of drugs administered in lipid-based delivery systems. Calcium ions are often added to digestion media to increase the extent of digestion of long-chain triglycerides (LCTs), but the effects they have on phase behaviour of the products of digestion, and consequent drug solubilization, are not well understood. This study investigates the effect of calcium and bile salt concentrations on the rate and extent of in vitro digestion of soybean oil, as well as the solubilizing capacity of the digestion products for two poorly water-soluble drugs, fenofibrate and danazol. In the presence of higher concentrations of calcium ions, the solubilization capacities of the digests were reduced for both drugs. This effect is attributed to the formation of insoluble calcium soaps, visible as precipitates during the digestions. This reduces the availability of liberated fatty acids to form mixed micelles and vesicles, thereby reducing drug solubilization. The use of high calcium concentrations does indeed force in vitro digestion of LCTs but may overestimate the extent of drug precipitation that occurs within the intestinal lumen.

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