• Archives of Pharmacal Research
• /
• v.2 no.2
• /
• 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.

• YAKHAK HOEJI
• /
• v.40 no.3
• /
• 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.

• YAKHAK HOEJI
• /
• v.44 no.3
• /
• 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
• /
• v.18 no.4
• /
• 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.

• YAKHAK HOEJI
• /
• v.50 no.1
• /
• 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
• /
• v.34 no.5
• /
• 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
• /
• v.18 no.5
• /
• pp.385-392
• /
• 2003

Biodegradable poly (L-lactide) (L-PLA) solution in methylene chloride was precipitated into microparticles by using supercritical carbon dioxide modified with polar cosolvents. The effects of the amount of polar cosolvents, solution concentration, temperature, and solution flow rate on the formation of microparticles were investigated. The mean particle size was found to increase with the increase of solution concentration and flow rate. It was also observed that the particle size not only increases but the size distribution also becomes less uniform as the temperature increases. The percent recovery of microparticles was found to be 30∼40% at all experimental conditions. The supercritical carbon dioxide modified with methanol and ethanol was employed to enhance the recovery, resulting in significant improvement up to about 80 and 70%, for methanol and ethanol, respectively. Furthermore, the mean diameter of L-PLA microparticles was found to be less than 1 $\mu\textrm{m}$ for both cosolvents.

• KSBB Journal
• /
• v.11 no.1
• /
• pp.100-106
• /
• 1996

The extraction of taxol and baccatin III from the ground needles of Taxus cuspidata were carried out by using supercritical carbon dioxide with and without cosolvents such as ethylacetate and methanol at 300 bar and 313K. Taxol is a promising anticancer agent and baccatin III is a precursor of semisysthesis of taxol. The taxol and baccatin III contents in the extracts were determined by a HPLC. The highest yields of taxol and baccatin III could be obtained by the supercritical extraction with 3wt% methanol and ethylacetate, respectively, as cosolvents. It was also found that the selectivity of taxol and baccatin III were 0.117 and 1.245wt%, respectively, with 0.7wt% ethylacetate, which demonstrated that the selectivity of taxol and baccatin III were increased about 1.8 and 19 times than those of conventional organic solvent extraction.

• YAKHAK HOEJI
• /
• v.42 no.1
• /
• 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
• /
• v.43 no.1
• /
• pp.27-32
• /
• 2005

We propose an effective and environmentally friendly dry stripping method using a supercritical carbon dioxide ($SCCO_2$) system modified by a single and multiple cosolvents to remove ion-implanted photoresist and residue from a wafer surface at three different temperatures (97, 148, $200^{\circ}C$) and pressures (200, 300, 400 bar). After high dose of ion implantation the photoresist was not easily removed by using pure $SCCO_2$, but swollen. The $SCCO_2$ system modified by single cosolvents and multiple cosolvents mixed with aprotic solvents could not effectively remove the heavy organics, but swell them. However, the $SCCO_2$ system modified with multiple cosolvent (5%, v/v) composed of DMSO and DIW showed high removal efficiency for ion-implanted photoresists at $97^{\circ}C$ and 200 bar for 30 min (about 80%). In this study it has been shown that the dry stripping method using $SCCO_2$ system modified with multiple cosolvents could replace either plasma ashing or acid and solvent wet bench method and dramatically reduce accompanied chemical usage and disposal.