YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
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Solubilization of CPD, a Novel Antivirus Compound Containing Pirimidine Structure, in Aqueous Solution

신규 피리미딘 구조를 함유한 항바이러스성 화합물 CPD의 수용액중 가용화

  • Song Sukgil (National Research Laboratory (NRL), College of Pharmacy, Chungbuk National University) ;
  • Kweon Ho-Seok (Samjin Pharn. Co., Ltd.) ;
  • Chung Youn Bok (National Research Laboratory (NRL), College of Pharmacy, Chungbuk National University)
  • 송석길 (충북대학교 약학대학 국가지정연구실) ;
  • 권호석 (삼진제약주식회사) ;
  • 정연복 (충북대학교 약학대학 국가지정연구실)
  • Published : 2006.02.01
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Abstract

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$^{(R)}$ RH40, Cremophor$^{(R)}$ EL, Poloxamer 407, Poloxamer 188) and a complexation agent [hydroxypropyl-${\beta}$-cyclodextrin (HPBCD)] , on the solubility of CPD in aqueous solution were evaluated. The solubility of CPD in water was under $1\;{\mu}g/ml$ at $20^{\circ}C$. Cosolvents such as ethanol, PG, PEG 300, PEG 400 and glycerin did not enhance the solubility of CPD at the $0{\sim}40\%$ 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$^{(R)}$ L, Cremophor$^{(R)}$ 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$^{(R)}$ L or Cremophor$^{(R)}$ 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 $4^{\circ}C$.

Keywords

References

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