Abstract
Directly 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.
Original language | English |
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Pages (from-to) | 677-682 |
Number of pages | 6 |
Journal | Drug Development and Industrial Pharmacy |
Volume | 33 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2007 |
Bibliographical note
Funding Information:The authors gratefully acknowledge support for this work by Control Delivery Systems, Inc. Watertown, Boston, MA. Thanks also due to Drs Paul Ashton, Grazyna Cynkowska, and Tadeusz Cynkowski, Control Delivery Systems, Inc., for helpful discussions and technical advice.
Funding
The authors gratefully acknowledge support for this work by Control Delivery Systems, Inc. Watertown, Boston, MA. Thanks also due to Drs Paul Ashton, Grazyna Cynkowska, and Tadeusz Cynkowski, Control Delivery Systems, Inc., for helpful discussions and technical advice.
Funders | Funder number |
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Control Delivery Systems Inc. |
Keywords
- 5-Fluorouracil
- Angiogenesis
- Chemical delivery
- Codrug
- Sustained release
- Trihydroxy steroid
ASJC Scopus subject areas
- Pharmacology
- Pharmaceutical Science
- Drug Discovery
- Organic Chemistry