• Archives of Pharmacal Research
• /
• 제2권2호
• /
• pp.85-88
• /
• 1979

Data on the solubility of p-hydroxy-benzoate in amide-water cosolvent system and surface tension of the binary amide-water cosolvents are analyzed in terms of the possible mechanism for cosolvency. The results of the study suggest that strong partitioning of the alkylated amides to the ester surface, thus reducing the hydrophobic interface within the system, nay account for much of the cosolvency phenomena observed in these systems.

• 약학회지
• /
• 제40권3호
• /
• pp.243-250
• /
• 1996

In order to formulate aqueous multivitamin solutions containing both oil-soluble (A, D, E) and water-soluble vitmains ($B_1,\;B_2,\;B_6,\;B_{12}$, C and niacinamide) in 1ml-dose, the effects of various additives such as cosolvents (propylene glycol, polyethylene glycol, glycerin), a sweetener (sorbitol) and a surfactant (Cremophor$^{\circledR}$ RH40) on the solubility of oil-soluble vitamins in water were evaluated. Cremophor$^{\circledR}$ RH40 showed the excellent capacity on the solubilization of oil-soluble vitamins, and the simultaneous addition of cosolvents and surfactant resulted in synergetic effects on the solubilization of oil-soluble vitamins. The effects of the combination of the cosolvents and sweetener on the stability of multivitamin solutions were also evaluated by determining the amount of vitmain A and $B_1$ remained in the solutions after storing at $40^{\circ}C$ for 9 weeks. The formulation consisting of Cremophor$^{\circledR}$ RH40 15%, PG 20%, and sorbitol 20% resulted in the best stability of vitamin A and $B_1$. The stability of vitamin A and $B_1$ in this formulation was evaluated at 50, 60, and $70^{\circ}C$ up to 40 days. The shelf-lives of vitamin A and $B_1$ in the formulation, calculated using the Arrhenius equation, were 1,521 days and 475 days at $20^{\circ}C$, respectively.

• 약학회지
• /
• 제44권3호
• /
• pp.263-271
• /
• 2000

In an attempt to develop an injectable form of practically insoluble biphenyl dimethyl dicarboxylate (DDB), the effect of various vehicles, cosolvents and hydrotropic agents was investigated. It was found that polyethylene glycol (PEG) 400 revealed the best solvency toward DDB (17.7 mg/ml at $37^{\circ}C$), and decreasing order of the solubility was as follows: PEG 400>PEG 300>diethylene glycol monoethyl ether (DGME)>PEG-8 glyceryl caprylate/caprate. Among the hydrotropes used, sodium salicylate, sodium benzoate and nicotinamide were effective in increasing the solubility in water. The solubility of DDB in 2 M sodium salicylate, sodium benzoate and nicotinamide solutions was increased 44.3, 23.5 and 44.0 times than that in water, respectively. The addition of sodium salicylate and sodium benzoate to PEG 300-water PEG 400-water and DGME-water cosolvents remarkably increased the solubility of DDB, and significantly retarded precipitate formation when mixed with water Hemolytic properties of DDB injections (2 mg/4~10 ml) in PEG 300-water or DGME-water (60:40 v/v) cosolvents containing sodium benzoate (0.14~0.35 M) were very low. It was concluded from the results that these solutions would be applied to the design of new DDB injections.

• Journal of Pharmaceutical Investigation
• /
• 제18권4호
• /
• pp.203-208
• /
• 1988

The stability and solubility of piroxicam in propylene glycol (PG), polyethylene glycol (PEC), and PG-water cosolvents have been studied by using high performance liquid chromatography. The degradation rate followed an apparent first-order kinetic and the reaction rate constants at 70, 80, and $90^{circ}C$ were determined. From these rate constants, the activation energy and the rate constant of piroxicam at $25^{circ}C$ in pure PG calculated by Arrhenius equation were 23.34 kcal/mole and $7.0\;{\times}\;10^{-4}\;day^{-1}$, respectively. Both of PG and PEG increased the solubility of the drug, but PEG was more effective.

• 약학회지
• /
• 제50권1호
• /
• pp.1-7
• /
• 2006

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 $4^{\circ}C$.

• Journal of Pharmaceutical Investigation
• /
• 제34권5호
• /
• pp.385-391
• /
• 2004

The purpose of the present study was to formulate the aqueous solution of $20-O-{\beta}-D-glucopyranosyl-20(S)-protopanaxadiol\;(IH-901)$, an intestinal bacterial metabolic derivative from Ginseng protopanaxadiol saponin. 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 $(Tween\;80,\;Cremophor^{\circledR}\;RH40,\;Cremophor^{\circledR}\;EL,\;Poloxamer\;407,\;Poloxamer\;188)$ and a complexation agent $[hydroxypropyl-{\beta}-cyclodextrin\;(HPBCD)]$, on the solubility of IH-90l in aqueous solution were evaluated. The solubility of IH-901 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 IH-901 at the 0 - 40% concentration range. The solubility of IH-901 was significantly elevated by the addition of cosolvents over the 80% concentration range. On the other hand, tween 80, $Cremophor^{\circledR}\;EL,\;Cremophor^{\circledR}\;RH40$ and HPBCD showed enhanced effects on the solubility of IH-901. The enhanced effects of Poloxamer 407 or Poloxamer 188 on the IH-901 solubility were less pronounced compared with $Cremophor^{\circledR}\;EL\;or\;Cremophor^{\circledR}\;RH40$. As a results, $Cremophor^{\circledR}$ aqueous solution was selected as an optimum solvent system. The aqueous solutions containing 10% $Cremophor^{\circledR}\;EL$ and 7% $Cremophor^{\circledR}\;RH40$ were formulated as dosing solutions containing 5.0 mg/ml of IH-901 for its intravenous and oral administration, respectively. The formular showed physical stability after stored for 7 days at $4^{\circ}C$.

• KSBB Journal
• /
• 제18권5호
• /
• pp.385-392
• /
• 2003

초임계 이산화탄소를 이용한 효율적인 DDS 설계를 위한 기초연구로서 순수한 초임계 이산화탄소와 초임계 이산화탄소와 상용성이 있으면서 고분자에 대해서는 비용매로 작용하는 극성 공용매로 변형된 초임계 이산화탄소를 이용하여 생체분해성 고분자인 L-PLA의 미세입자 형성에 대하여 고찰하였다. L-PLA용액의 농도가 증가할수록 입자 크기는 증가하였으며, 약 4%이상의 농도에서는 입자들 간의 강한 응집으로 인하여 입자의 형태가 구형에서 섬유상으로 변화하였다. 침전기 내 초임계 유체의 온도가 높아짐에 따라 생성된 입자의 크기가 증가하였으며, 온도가 높아질수록 입자의 분포는 불균일하게 나타났다. 용액 유량이 증가함에 따라 전체적으로 구형 입자의 생성이 증가하였으며, 입자의 평균 크기는 증가하는 것으로 나타났다. 순수한 초임계 이산화탄소를 사용한 경우 모든 실험 조건에서 입자 회수율은 약 30∼40% 정도로 나타났다. 입자 회수율을 향상시키기 위해 극성 공용매를 초임계 이산화탄소와 혼합하여 입자를 제조하였다. 메탄올과 에탄올을 이산화탄소 대비 몰비 0.5로 혼합한 경우 회수율은 각각 80%와 70%로 매우 높은 값을 나타냈으며, 평균 직경 1 $\mu\textrm{m}$이하의 매우 작은 입자를 제조할 수 있었다.

• KSBB Journal
• /
• 제11권1호
• /
• pp.100-106
• /
• 1996

300bar와 313K에서 초임계 이산화탄소와 에틸아세테이트와 메탄올을 보조용매로 사용하여 주목나무로부터 taxol과 baccatin III를 추출하는 실험을 한 결과 추출되어지는 taxol의 추출량은 보조용매로 사용된 에틸아세테이트의 농도에는 영향을 받지 않았으며 3wt%의 메탄올을 사용했을 때 가장 많은 양이 추출되었고 taxol의 선택성은 보조용매로 에틸아세테이트를 사용했을 때 0.117mass%로 가장 높게 나타났다. Baccatin III는 보조용매로 에틸아세테이트를 사용하면 유기용매 추출량과 거의 같은 양이 추출되어지며 이 때의 선택성은 0.7wt% 에틸아세테이트에서 1.245wt%, 3.0wt% 에틸아세테이트에서 1.115wt%로 유기용매 추출에 비해 19배까지 크게 증가하였으며 3wt%의 메탄올을 사용했을 때에는 약 6.4배 증가하였다. 여기서 에틸아세테이트는 baccatin III를 추출하는데 있어 수율과 선택성면에서 가장 효과적인 보조용매라는 것을 알 수 있다. 또한 시료를 n-hexane으로 처리하면 비극성 물질은 상당히 제거되나 그 과정에서 많은 양의 taxol 과 baccatin III가 손실될 뿐만 아니라 선택성도 증가하지 않으므로 공정상 불필요하며 보조용매를 사용한 초임계유체 추출이 주목나무로부터 특정성분을 추출하는데 아주 효과적이라는 것을 알 수있다.

• 약학회지
• /
• 제42권1호
• /
• pp.59-69
• /
• 1998

To increase the solubility of quercetin, which is a practically insoluble flavonoid of Ginkgo biloba leaf, the effects of nonaqueous vehicles. Their cosolvents, water-sol uble polymers and modified cyclodextrins (CDs) were observed. Polyethylene glycols, diethyleneglycol monoethyl ether, and their cosolvents with water showed a good solvency toward quercetin. Also the aqueous solutions of povidone, copolyvidone and Cremophor RH 40 was effective in solubilizing quercetin. Complex formation of quercetin with ${\beta}$-cyclodextrin (${\beta}$-CD), dimethyl-${\beta}$-cyclodextiin (DMCD), 2-hydroxypropyl-${\beta}$-cyclodextrin (HPCD) and ${\beta}$-cyclodextrin sulfobutyl ether (SBCD) in water was investigated by solubility method at $37^{\circ}C$. The addition of CDs in water markedly increased the solubility of quercetin with increasing the concentration. AL type phase solubility diagrams were obtained with CDs studied. Solubilizaton efficiency by CDs was in the order of SBCD >> DMCD > HPCD > ${\beta}$-CD. The dissolution rates of quercetin from solid dispersions with copolyvidone, povidone and HPCD were much faster than those of drug alone and corresponding physical mixtures, and exceeded the equilibrium solubility (3.03${\pm}1.72{\mu}$g/ml). The permeation of quercetin through duodenal mucosa did not occur even in the presence of enhancers such as bile salts, but the permeation was observed when the mucus layer was scraped off. This was due to the fact that quercetin had a strong binding to mucin ($58.5{\mu}$g/mg mucin). However rutin was permeable to the duodenal mucosa. The addition of enhancer significantly increased the permeation of rutin in the order of sodium glycocholate.

• Korean Chemical Engineering Research
• /
• 제43권1호
• /
• pp.27-32
• /
• 2005

본 연구에서는 다양한 공용매로 변형된 초임계 이산화탄소를 이용하여 웨이퍼 표면에 존재하는 이온주입 포토레지스트(IIP, ion-implanted photoresist) 및 잔류 불순물의 제거 공정을 97, 148, $200^{\circ}C$의 온도와 200, 300, 400 bar의 압력조건에서 수행하였다. 이온주입 포토레지스트는 순수 초임계 이산화탄소에 의해 제거되지 않았으나 팽윤(swelling)되는 것을 확인할 수 있었다. 또한, 단일 공용매 및 비양성자성 용매들의 혼합 공용매로 변형된 초임계 이산화탄소 시스템은 이온주입 포토레지스트를 팽윤시키나, 제거에 효과적이지 못하였다. 그러나 DMSO에 DIW가 혼합된 혼합 공용매(5%, v/v)로 변형된 초임계 이산화탄소 시스템은 $97^{\circ}C$, 200 bar의 온도, 압력 조건에서 30분 동안 세정 실험을 수행한 결과 이온 주입 포토레지스트의 제거에 효과적이었다(약 80%). 본 연구에서 사용된 혼합 공용매로 변형된 초임계 이산화탄소 시스템은 플라즈마 애싱(ashing) 및 산과 용매가 기본이 되는 습식 세정 방법의 대안으로서 화학액의 사용과 폐수를 감소시킬 수 있다.