Solid dispersions with polyethylene glycol

Crystallinity of 9 in solid dispersions with polyethylene glycol (PEG 400) and urea was measured by IR and X-ray diffraction methods (00JPS79). 

Fernandez M, Margarit MV, Rodriguez IC, Cerezo A. Dissolution kinetics of piroxicam in solid dispersions with polyethylene glycol-4000. Int J Pharm 1993 98 29-35. 

Van den Mooter, G. Augustijns, P. Blaton, N. Kinget, R. Physico-Chemical characterization of solid dispersions of temazepam with polyethylene glycol 6000 and PVP K30. Int. J. Pharm. 1998, 164, 67-80. 

Polyethylene glycols can also be used to enhance the aqueous solubility or dissolution characteristics of poorly soluble compounds by making solid dispersions with an appropriate polyethylene glycol. Animal studies have also been performed using polyethylene glycols as solvents for steroids in osmotic pumps. 

Solid dispersion of acetohexamide was studied by Graf et al (12-14) using different polymers and various ratios. Coprecipitates of acetohexamide with polyethylene glycol (PEG 6000) were prepared by the solvent method with ethanol (crystalline form I) or with chloroform (crystalline form III). Phase diagrams... 

The phase equilibria produced with polyethylene glycol may be quite complicated because of the ability of drugs to disperse molecularly within the polymer chains [105]. Thus, the systems may display solid solution and glass formation [103] due to a relatively high solubility of the drug in polymer, e.g. indomethacin, or a virtual monotectic due to a very limited solubility of the drug in the polymer, e.g. the triamterene - PEG system [106]. 

Adsorption on solid matrices, which improves (at optimal protein/support ratios) enzyme dispersion, reduces diffusion limitations and favors substrate access to individual enzyme molecules. Immobilized lipases with excellent activity and stability were obtained by entrapping the enzymes in hydrophobic sol-gel materials [20]. Finally, in order to minimize substrate diffusion limitations and maximize enzyme dispersion, various approaches have been attempted to solubilize the biocatalysts in organic solvents. The most widespread method is the one based on the covalent linking of the amphiphilic polymer polyethylene glycol (PEG) to enzyme molecules [21]. 

The formation of peroxides and formaldehyde in the high-purity polyoxyethylene surfactants in toiletries has been shown to lead to contact dermatitis [31], Peroxides in hydrogenated castor oil can cause autoxidation of miconazole [32], Oxidative decomposition of the polyoxyethylene chains occurs at elevated temperature, leading to the formation of ethylene glycol, which may then be oxidized to formaldehyde. When polyethylene glycol and poloxamer were used to prepare solid dispersions of bendroflumethiazide, a potent, lipophilic diuretic drug, the drug reacted with the formaldehyde to produce hydroflumethiazide [33],... 

Fused silica capillary columns of various internal bores and of lengths in the range 25 to 50 m are mainly employed for analytical separations. A variety of polar and non-polar column types are available including those open tubular types with simple wall coatings (WCOT), those with coatings dispersed on porous solid-supports to increase adsorbent surface area (SCOT) and porous layer open tubular (PLOT) columns. Important stationary phases include polyethylene glycol, dimethylpolysiloxane and different siloxane copolymers. Various sample introduction procedures are employed including ... 

Solid dispersions have been explored as drug delivery systems for over 30 years, initially starting with various forms of polyethylene glycols, citric and succinic acids, and sugars. However, more recent success has been achieved using hydroxypropy-lcellulose (HPC), ethylcellulose (EC), and the commercial forms of methylacrylic acids and their copolymers sold under the name Eudragits. In addition, chitosans have been evaluated for this purpose. 

In another example of a polyethylene glycol/surfactant, solid dispersion is presented by Dannenfelser et al. (2004) with a poor water-insoluble drug exhibiting only a g1i7iL aqueous solubility. At 40 mg/mL, the PEG 3350/polysorbate 80 solid dispersion exhibited similar exposure as that of a cosolvent-surfactant solution and a ten-time increase over a dry blend formulation, thus enabling a solid oral dosage form for clinical trials. 

The combination of solid-state ATR-IR and solid-state NMR data supported the conclusion that the presence of crystalline material was responsible for changes in the dissolution profiles of the different lots. The results appear consistent with historical examples of changes in API physical form of solid, high molecular weight, polyethylene glycol dispersion formulations of amorphous indomethacin and griseofulvin (92-95). 

In studies involving human exposure (Rengstorff and Mershon, 1969a, b), CS (0.1% or 0.25% in water 1.0% in triocyl phosphate) sprayed or administered as ophthalmic drops onto the eyes, caused apraxia of eyelid opening with blepharospasm upon eyelid closure for 10 to 135 s. It also caused a transient conjunctivitis but no comeal damage upon further inspection with a slit lamp. Rabbit eyes contaminated with CS as a solution (0.5-10% in polyethylene glycol), as a solid, or thermally dispersed as a smoke (15 min at 6,000 mg/m ) showed a greater toxicity with solution. CS in solution caused profuse lacrimation, conjunctivitis, iritis, chemosis, keratitis, and corneal vascularization at concentrations at or above 1%. 

M Alden, J Tegenfeldt, ES Saers. Structures formed by interactions in solid dispersions of the system polyethylene glycol griseofulvin with charged and non-charged surfactants added. Int J Pharm 94 31-38, 1993. 

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