A Novel Chemical Delivery System Comprising an Ocular Sustained Release Formulation of a 3α, 17α, 21-trihydroxy-5β-pregnan-20-one-BIS-5-Flourouracil Codrug

ABSTRACTDirectly compressed sustained release pellets were prepared from material consisting of a molecule of 3α, 17α, 21-trihydroxy-5β-pregnan-20-one (trihydroxy steroid, THS) covalently linked via carbonate moieties to two molecules of 5-flourouracil (5FU) to form a novel THS-BIS-5FU codrug for th...

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Bibliographic Details
Published in:Drug development and industrial pharmacy 2007-01, Vol.33 (6), p.677-682
Main Authors: Howard-Sparks, Michelle, Al-Ghananeem, Abeer M., Crooks, Peter A., Pearson, Andrew P.
Format: Article
Language:English
Subjects:
5-Fluorouracil
Angiogenesis
Biological and medical sciences
Chemical delivery
Codrug
General pharmacology
Medical sciences
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Sustained release
Trihydroxy steroid
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Summary:ABSTRACTDirectly compressed sustained release pellets were prepared from material consisting of a molecule of 3α, 17α, 21-trihydroxy-5β-pregnan-20-one (trihydroxy steroid, THS) covalently linked via carbonate moieties to two molecules of 5-flourouracil (5FU) to form a novel THS-BIS-5FU codrug for the treatment of angiogenisis. Dissolution and drug release was tested in vitro in 0.1M phosphate buffer (pH 7.4), human serum, and vitreous humor. The results suggest that neat THS-BIS-5FU codrug pellets are useful for sustained release ocular delivery of the parent compounds, and that the unique physicochemical properties of the codrug allow slow dissolution and rapid release of the two parent drugs. This codrug formulation is regarded as a "chemical delivery" system that involves dissolution of the codrug as the rate-limiting step followed by rapid hydrolysis of the carbonate ester linkages to release the parent drugs via sustained delivery.
ISSN:0363-9045
1520-5762
DOI:10.1080/03639040601134108