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신규 피리미딘 구조를 함유한 항바이러스성 화합물 CPD의 수용약중 가용화
송석길(Sukgil Song),권호석(Ho Seok Kweon),정연복(Youn Bok Chung) 대한약학회 2006 약학회지 Vol.50 No.1
The purpose of the present study was to formulate the aqueous solution of 1-cyclopent-3-enylmethyl-6(3,5-dimethyl-benzoyl)-5-ethyl-1H-pyrimidine-2,4-dione (CPD), a novel antivirus compound containing pirimidine structure. For this purpose, the effects of various solubilization agents such as cosolvents [ethanol, propylene glycol (PG), polyethylene glycol 300 (PEG 300), polyethylene glycol 400 (PEG 400), glycerin], surfactants (Tween 80, Cremophor?? RH40, Cremophor?? EL, Poloxamer 407, Poloxamer 188) and complexation agent [hydroxypropyl-β-cyclodextrin (HPBCD)], on the solubility of CPD in aqueous solution were evaluated. The solubility of CPD in water was under 1 ㎍/㎖ at 20℃. Cosolvents such as ethanol, PG, PEG 300, PEG 400 and glycerin did not enhance the solubility of CPD at the 0~40% concentration range. The solubility of CPD was significantly elevated by the addition of cosolvents over the 80% concentration range. On the other hand, tween 80, Cremophor?? L, Cremophor?? RH40, and HPBCD showed enhanced effects on the solubility of CPD. The enhanced effects of Poloxamer 407 or Poloxamer 188 on the CPD solubility were less pronounced compared with tween 80, Cremophor?? L or Cremophor?? RH40. As a results, tween 80 aqueous solution was selected as an optimum solvent system. The aqueous solutions containing 20% tween 80 were formulated as a dosing solution containing CPD for its intraperitoneal and intrahypodermic administration, respectively. The formular showed physical stability after stored for 7 days at 4℃. Keywords : CPD, solubility, stability, cosolvent, surfactant
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