Solubilization by Cosolvents I: Organic Solutes in Propylene Glycol-Water Mixtures

Yalkowsky, Samuel H.; Rubino, Joseph T.

doi:10.1002/jps.2600740410

Cited by 113 publications

(60 citation statements)

References 13 publications

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“…Cosolvent addition is a highly effective technique for enhancement of solubility of poorly soluble drugs [10,17]. The small nonpolar hydrocarbon region in the cosolvent can reduce the ability of the aqueous system to squeeze out nonpolar solutes.…”

Section: Solubility Of Etoricoxib In Water-cosolvent Systemsmentioning

confidence: 99%

“…The advantage of cosolvent technology enhancing drug solubility in a liquid-based formulation includes [8] convenience, removing the need for mixing solvent before administration; safety, avoiding contamination in the dispensing process; inexpensive, no need for expensive pharmaceutical technology for formulation of dosage form. The most frequently used low-toxicity cosolvents for parenteral use are propylene glycol, ethanol, glycerin, polyethylene glycol (PEG), dimethylsulfoxide (DMSO), and dimethylacetoamide (DMA) [9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

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Solubility Enhancement of Etoricoxib by Cosolvency Approach

Nayak

Panigrahi

2012

ISRN Physical Chemistry

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The purpose of the present study was to examine and compare the cosolvency using three different cosolvents, namely PEG 400, PG, and glycerin on the aqueous solubility enhancement of a poorly aqueous soluble drug, etoricoxib, since solubilization of nonpolar drugs constitutes one of the important tasks in the formulation design of liquid dosage forms. The aqueous solubility of etoricoxib was 0.0767 ± 0.0018 mg/mL, which was significantly improved by the addition of PEG 400, PG, and glycerin as cosolvents. It was scrutinized that the less-polar solvents were found to increase the aqueous solubility by greater extent, thus accentuating hydrophobic interaction mechanism. Among various solvent-cosolvent blends investigated, water-PEG 400 showed highest solubilization potential. Thus, the study generated an important array of data to compare the effect of these cosolvents on the aqueous solubility of etoricoxib.

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Section: Solubility Of Etoricoxib In Water-cosolvent Systemsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Solubility Enhancement of Etoricoxib by Cosolvency Approach

Nayak

Panigrahi

2012

ISRN Physical Chemistry

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“…8,16 log S mix = log S + Φ V ss (1) where S mix and S are the solubilities of drug in solvent mixture and pure solvent, respectively. V ss is the volume fraction of the stronger solvent and Φ is the solubilization power of the stronger solvent.…”

Section: Solubility In Mixed-solvent Systemsmentioning

confidence: 99%

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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“…One of the major challenges of present pharmaceutical research is to enhance the dissolution profile, absorption efficiency and bioavailability of water insoluble drugs (Yalkowsky and Rubino, 1985). The solubilitydissolution behavior of a drug is frequently the rate-limiting step to absorption of drugs from the gastrointestinal tract for orally administered drugs (Sugawara et al, 2005;Youn et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Preparation and comparative evaluation of liquisolid compacts and solid dispersions of Valsartan

2012

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The aim of the present study was to increase the solubility of a poorly water soluble BCS class II drug, valsartan. Liquisolid technology and solid dispersion by kneading method were techniques used to improve the solubility of the drug by using non-volatile solvents and some hydrophilic carriers. Liquisolid compacts were prepared by dissolving the drug in suitable non volatile solvents. The various non volatile solvents used were PG, PEG, and glycerine. The carrier coating materials play an important role in improving the solubility of the drug. The dissolution rate of the drug was increased by using propylene glycol as non-volatile solvent at 20:1 ratio of carrier to coating material. Solid dispersion by kneading method were another attempt to improve solubility the various carrier materials used were PVP K 30, PEG 6000 and mannitol, these carriers are used in various ratios to improve its solubility. The dissolution rate of drug using solid dispersion kneading method with mannitol was increased at 1:3 ratio. The DSC and FTIR studies revealed no drug excipients interactions, whereas XRD revealed the reduced crystalinity of drug, which showed enhanced solubility. From the results it was concluded that the liquisolid compacts enhanced the solubility of valsartan in comparison to traditional solid dispersion method.

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Solubilization by Cosolvents I: Organic Solutes in Propylene Glycol-Water Mixtures

Cited by 113 publications

References 13 publications

Solubility Enhancement of Etoricoxib by Cosolvency Approach

Solubility Enhancement of Etoricoxib by Cosolvency Approach

Solubility enhancement of cox-2 inhibitors using various solvent systems

Preparation and comparative evaluation of liquisolid compacts and solid dispersions of Valsartan

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