Synergistic effect of PEG-400 and cyclodextrin to enhance solubility of progesterone

ConclusionPEG-400, polysorbate 80, and 2 CDs (Trappsol HPB and Captisol) were used in an attempt to improve the aqueous solubility of a model hydrophobic drug, progesterone. The aqueous solubility of progesterone improved significantly from 0.007 mg/mL by the addition of PEG-400, CDs, and polysorbate 80. In systems containing various amounts of PEG-400 and 3% Trappsol HPB in water (% wt/wt), the theoretical solubility was calculated by adding the solubilities in the individual systems. The observed solubility values were up to 96% higher than the theoretical values. The effect of synergism was significant in 5% to 50% PEG-400/water systems containing Trappsol HPB. Systems containing Captisol did not show such synergistic effects. In general, the addition of polysorbate 80 to the PEG-400/water systems containing CDs affected synergism negatively.

[1]  P. Mura,et al.  Effect of water-soluble polymers on naproxen complexation with natural and chemically modified beta-cyclodextrins. , 2001, Drug development and industrial pharmacy.

[2]  J. Pitha,et al.  Effects of ethanol on formation of inclusion complexes of hydroxypropylcyclodextrins with testosterone or with methyl orange , 1992 .

[3]  Thorsteinn Loftsson,et al.  Cyclodextrin complexation of NSAIDSs: physicochemical characteristics , 1993 .

[4]  Jeffrey Millard,et al.  Solubilization by cosolvents. Establishing useful constants for the log-linear model. , 2002, International journal of pharmaceutics.

[5]  E. Stefánsson,et al.  Cyclodextrin solubilization of benzodiazepines: formulation of midazolam nasal spray. , 2001, International journal of pharmaceutics.

[6]  M. Aldén,et al.  Solid state studies of drug-cyclodextrin inclusion complexes in PEG 6000 prepared by a new method. , 1999, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[7]  J. Zung,et al.  Influence of alcohol addition on the .gamma.-CD:pyrene complex , 1991 .

[8]  S. Yalkowsky,et al.  Combined effect of cosolvent and cyclodextrin on solubilization of nonpolar drugs. , 1999, Journal of pharmaceutical sciences.

[9]  M. Rand,et al.  Blood levels of nicotine and physiological effects after inhalation of tobacco smoke. , 1969, European journal of pharmacology.

[10]  Alfred N. Martin Physical Pharmacy: Physical Chemical Principles in the Pharmaceutical Sciences , 1969 .

[11]  T. Loftsson,et al.  Cyclodextrin solubilization of ETH-615, a zwitterionic drug. , 1998, Drug development and industrial pharmacy.

[12]  K. Järvinen,et al.  Co-Administration of a Water-Soluble Polymer Increases the Usefulness of Cyclodextrins in Solid Oral Dosage Forms , 1998, Pharmaceutical Research.

[13]  M. Brewster,et al.  Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization. , 1996, Journal of pharmaceutical sciences.