MEDI 321 |
| The prostacyclin analog treprostinil has been formulated and marketed as Remodulin® (treprostinil sodium), a parenteral therapy for Pulmonary Arterial Hypertension (PAH). Treprostinil is a weak acid with poor aqueous solubility and is not a good candidate for oral delivery because of dissolution-rate limited absorption. The sodium salt has poor physicochemical characteristics for a solid dose formulation, so a number of other pharmaceutically-acceptable counterions were considered. Diethanolamine was selected as the ideal counterion for the oral delivery of treprostinil based on the salt's solubility, hygroscopicity and melting temperature. Several formulations were evaluated to achieve sustained treprostinil plasma concentrations following zero-order release. This talk will briefly discuss the parenteral form of treprostinil and the development of treprostinil diethanolamine as an oral solid-dosage form for the treatment of PAH. In vitro dissolution data and in vivo pharmacokinetic data will be presented in support of an oral twice a day dosing regimen. |
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Medicinal Chemistry of Rare Diseases
1:30 PM-5:00 PM, Wednesday, 13 September 2006 Moscone Center -- Room 103, Oral
Division of Medicinal Chemistry |