Solubilization of cyclosporin A

Ran, Yingqing; Zhao, Ling; Xu, Qingyang; Yalkowsky, Samuel H.

doi:10.1208/pt020102

Cited by 64 publications

(42 citation statements)

References 11 publications

(12 reference statements)

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“…7,8,15 The small nonpolar hydrocarbon region in the cosolvent can reduce the ability of the aqueous system to squeeze out nonpolar solutes. The mixed-solvent systems in the present study include ethanol-PEG 400, glycerol-ethanol, and water-ethanol.…”

Section: Solubility In Mixed-solvent Systemsmentioning

confidence: 99%

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Solubility enhancement of cox-2 inhibitors using various solvent systems

2003

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INTRODUCTIONThis study examined the solubility enhancement of 4 cox-2 inhibitors, celecoxib, rofecoxib, meloxicam, and nimesulide, using a series of pure solvents and solvent mixtures. Water, alcohols, glycols, glycerol, and polyethylene glycol 400 (PEG 400) were used as solvents and water-ethanol, glycerol-ethanol, and polyethylene glycol-ethanol were used as mixed-solvent systems. A pH-solubility profile of drugs was obtained in the pH range 7.0 to 10.9 using 0.05M glycine-sodium hydroxide buffer solutions. Lower alcohols, higher glycols, and PEG 400 were found to be good solvents for these drugs. The aqueous solubility of celecoxib, rofecoxib, and nimesulide could be enhanced significantly by using ethanol as the second solvent. Among the mixedsolvent systems, PEG 400-ethanol system had highest solubilization potential. In the case of meloxicam and nimesulide, solubility increased significantly with increase in pH value. Physico-chemical properties of the solvent such as polarity, intermolecular interactions, and the ability of the solvent to form a hydrogen bond with the drug molecules were found to be the major factors involved in the dissolution of drugs by pure solvents. The greater the difference in the polarity of the 2 solvents in a given mixed solvent, the greater was the solubilization power. However, in a given mixedsolvent system, the solubilization power could not be related to the polarity of the drugs. Significance of the solubility data in relation to the development of formulations has also been discussed in this study.Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely prescribed medications in the world. As a therapeutic class, NSAIDs exhibit analgesic, antiinflammatory, antipyretic, and platelet inhibitory properties. 1,2 However, these drugs have serious side effects such as gastrointestinal (GI) toxicities, gastric mucosal ulcerations and hemorrhage due to inhibition of prostaglandin production.3,4 The mechanism of action of NSAIDs has been attributed to their ability to inhibit the cyclooxygenase enzyme (cox). Out of the 2 isoforms of cyclooxygenase, cox-1 is responsible for mediating the production of prostaglandin while cox-2 is primarily associated with inflammation, pain, and fever. 5,6 The traditional NSAIDs are nonselective cox inhibitors. Cox-2 selective NSAIDs are, therefore, ideal anti-inflammatory drugs with minimum drug-related side effects, since they spare cox-1 activity.The very poor aqueous solubility and wettability of cox-2 inhibitors, however, give rise to difficulties in the design of pharmaceutical formulations and lead to variable oral bioavailability. The use of cosolvents has been employed by a number of workers [7][8][9] to enhance the solubility of poorly soluble drugs. Some attempts have been made to increase the solubility of nimesulide and meloxicam 10-13 by using techniques other than the use of cosolvents. Enhancement of solubility of celecoxib and rofecoxib has not received much attention so far. In the present study, an attempt has b...

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Section: Solubility In Mixed-solvent Systemsmentioning

confidence: 99%

“…The use of cosolvents has been employed by a number of workers [7][8][9] to enhance the solubility of poorly soluble drugs. Some attempts have been made to increase the solubility of nimesulide and meloxicam [10][11][12][13] by using techniques other than the use of cosolvents.…”

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confidence: 99%

Solubility enhancement of cox-2 inhibitors using various solvent systems

2003

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“…The logarithmic relationship between total drug solubility (S tot ) in a mixed solvent and cosolvent concentration (C cosol ) can be described by Equation (1) [18] [19]. log log…”

Section: Resultsmentioning

confidence: 99%

Aqueous Solubility Enhancement of Mirtazapine: Effect of Cosolvent and Surfactant

Ezealisiji¹,

Mbah²,

Osadebe³

2015

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The poor aqueous solubility of drugs is a challenging problem faced by pharmaceutical scientists in drug formulation. Cosolvency and micellization techniques have been severally used to enhance the solubility of poorly aqueous soluble drugs. Mirtazapine, a tetracyclic antidepressant used for the treatment of moderate to severe depression and anxiety, has very poor aqueous solubility. The objective of the study was to investigate the effect of solubilizing agents (cosolvents and surfactants) on the aqueous solubility of mirtazapine while envisaging that any significant improvement in its aqueous solubility could contribute towards alleviating the withdrawal symptoms often associated with the drug. The solubility of mirtazapine was determined at room temperature in aqueous mixtures of cosolvents (propylene glycol and polyethylene glycol 400) and surfactants (polysorbate 20, polysorbate 80 and sodium lauryl sulfate). An exponential increase in mirtazapine solubility was observed when total drug solubility in water-cosolvent system was plotted against cosolvent fraction volume. Polyethylene glycol 400 gave larger solubilization capacity (σ) when compared to propylene glycol. With the surfactants, linear relationship between the total solubility of the drug in water-surfactant mixtures and surfactant concentration was noted. Sodium lauryl sulfate showed the largest solubilization power (k) when compared to the nonionic surfactants (polysorbate 20 and polysorbate 80 respectively). A linear relationship between standard free energy and partition coefficient was also observed. The result of the study shows that aqueous solubility of mirtazapine is significantly improved by cosolvency and micellization and therefore there exists the possibility of improving the withdrawal symptoms often experienced with the drug. It also suggests that large free energy is required for drugs with high partition coefficients to permeate the biological membrane.

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“…The solubility figures (Fig 5-10) showed the exponential increase in the solubility of drugs with increasing concentration of cosolvents [14][15][16][17][18] . By disrupting water's self-association, cosolvents reduce water's ability to squeeze out non-polar, hydrophobic compounds, thus increasing solubility.…”

Section: Cosolvent Solubilizationmentioning

confidence: 99%

Untitled

2012

IJPSR

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Celecoxib, a diaryl substituted pyrazole, is practically insoluble in water which precludes its use in parenteral and liquid dosage forms. This study explores the solubility enhancement of celecoxib using hydrotropy and cosolvency solubilization approaches. The equilibrium solubility studies were performed using hydrotropes piperazine, sodium citrate, and urea and cosolvents PEG 200, PEG 400, PEG 600, DMA, Ethanol and Propylene glycol at various temperatures. Parenteral formulations using hydrotrope and cosolvents were developed and studied for accelerated stability study. The solubility of celecoxib was found to increase upto 45 times in 3M piperazine solution and upto 10232 times in PEG 600 at 25±2 0 C. The results of solubilization study showed that the increase in solubility of celecoxib is smaller in piperazine and urea when used alone as compared to the increase in solubility which was found when these hydrotropes were used in combination with cosolvents PEG 600, PEG 400, DMA and Eth. Stability studies indicated that all the formulations stored were found to be stable for drug content, pH and change in physical appearance i.e. color, precipitation.

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Solubilization of cyclosporin A

Cited by 64 publications

References 11 publications

Solubility enhancement of cox-2 inhibitors using various solvent systems

Solubility enhancement of cox-2 inhibitors using various solvent systems

Aqueous Solubility Enhancement of Mirtazapine: Effect of Cosolvent and Surfactant

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