N. Hioka, R. Chowdhary, Namrata Chansarkar
Oct 1, 2002
Citations
3
Influential Citations
42
Citations
Journal
Canadian Journal of Chemistry
Abstract
The synthetic route for the benzoporphyrin derivatives produces two regioisomers in equimolar quantities (ring A and B isomers). A derivative of the A-ring product, BPD-MA (benzoporphyrin-derivative monoacid ring A, verteporfin), has recently been approved in North America and Europe for the treatment of age-related macular degen- eration. The B-ring isomers, contrary to the A-ring isomers, exhibit high aggregation in many formulations, which re- sults in inadequate drug delivery for clinical uses. To avoid aggregation, a non-ionic surfactant polymer such as a Pluronic — poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) — may be used as a formulation excipient. The triblock polymer investigated here is designated P123 (or poloxamer 403). When used to formulate a monoacid benzoporphyrin B-ring derivative (2), a critical micelle concentration of P123 in water occurred at approxi- mately 0.015 to 0.03%. The apparent pKa of compound 2 was dependent on its concentration in P123, and decreased as the molar ratio (P123:2) increased. High concentrations of P123 and neutral pH were found to be the best condi- tions to maintain the drug in its monomeric form. Kinetic studies suggest that the aggregate of 2 contains several mol- ecules, and is formed by a catalyzed self-assembly process. Samples with 1 mg mL -1 of drug, at pH = 7.4, and 4.8% of Pluronic showed satisfactory capacity to load and keep monomers stable. This formulation has potential PDT appli- cations.