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An investigation into the structure and bioavailability of α-tocopherol dispersions in Gelucire 44/14

Barker, S.A., Yap, S.P., Yuen, K.H., McCoy, C.P., Murphy, J.R., Craig, D.Q.M. (2003) An investigation into the structure and bioavailability of α-tocopherol dispersions in Gelucire 44/14. Journal of Controlled Release, 91 (3). pp. 477-488. ISSN 0168-3659. (doi:10.1016/S0168-3659(03)00261-X) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:78865)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. (Contact us about this Publication)
Official URL
https://doi.org/10.1016/S0168-3659(03)00261-X

Abstract

In this investigation we describe the preparation, physical characterisation and in vivo behaviour of solid dispersions of a liquid nutraceutical, α-tocopherol, in Gelucire 44/14 with a view to establishing whether dispersion in this matrix may provide a means of formulating a liquid drug in a solid dosage form while also improving the oral bioavailability. Using Vitamin E Preparation USP as the source of α-tocopherol, dispersions were prepared using a melt-fusion method with active loadings up to 50% (w/w) and characterised using differential scanning calorimetry and optical microscopy. Capsules containing 300 IU α-tocopherol were manufactured and the absorption profiles compared to a commercial soft gelatin capsule preparation in healthy human volunteers. Confocal laser scanning microscopy (CLSM) studies were performed in order to elucidate the mechanism by which drug release may be occurring. Differential scanning calorimetry studies indicated that the presence of the active had a negligible effect on the melting profile of the carrier, indicating limited miscibility between the two components, a conclusion supported by the microscopy studies. Similarly, the dispersions were shown to exhibit a glass transition corresponding to the incorporated drug, indicating molecular cooperativity and hence phase separation from the lipid base. Despite the phase separation, it was noted that capsules stored for 18 months under ambient conditions showed no evidence of leakage. Bioavailability studies in six healthy male volunteers indicated that the Gelucire 44/14 formulation showed an approximately two-fold increase in total α-tocopherol absorption compared to the commercial preparation. Confocal laser scanning microscopy studies indicated that, on contact with water, the dispersions formed two interfacial layers, from which the Gelucire 44/14 disperses in the liquid medium as small particles. Furthermore, evidence was obtained for the dispersed material becoming incorporated into the hydrated lipid. In conclusion, the dispersion of the liquid drug in Gelucire 44/14 appears to allow the dual advantages of the preparation of a solid formulation and improved bioavailability of this material.

Item Type: Article
DOI/Identification number: 10.1016/S0168-3659(03)00261-X
Uncontrolled keywords: Bioavailability, Confocal, Differential scanning calorimetry, Gelucire, Glyceride, Microscopy, Solid dispersion, Tocopherol, Vitamin E, Absorption, Differential scanning calorimetry, Dispersions, Glass transition, Optical microscopy, Confocal laser scanning microscopy (CLSM), Drug products, alpha tocopherol, gelucire, adult, article, confocal laser microscopy, controlled drug release, controlled study, differential scanning calorimetry, dispersion, drug absorption, drug bioavailability, drug delivery system, drug dosage form, drug formulation, drug storage, drug structure, human, human experiment, male, microcapsule, microscopy, miscibility, normal human, phase separation, priority journal
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Susan Barker
Date Deposited: 27 Nov 2019 12:43 UTC
Last Modified: 27 Nov 2019 12:43 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/78865 (The current URI for this page, for reference purposes)
Barker, S.A.: https://orcid.org/0000-0003-4880-0253
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