APPLICATIONS IN PHARMACEUTICAL FORMULATION OR TECHNOLOGY
Polyethylene glycols are widely used in a variety of pharmaceutical formulations including parenteral, topical, ophthalmic, oral and rectal preparations.
Polyethylene glycols are stable, hydrophilic substances that are essentially nonirritant to the skin. Although they do not readily penetrate the skin, polyethylene Glycols are water soluble and as such are easily removed from the skin by washing; they are therefore useful as ointment bases. Solid grades are generally employed in topical ointments with the consistency of the base being adjusted by the addition of liquid grades of polyethylene glycol.
Mixtures of polyethylene glycols can be made higher to withstand exposure to warmer climates; release of the drug is not dependent upon melting point; physical stability on storage is better; suppositories are readily miscible with rectal fluids. Disadvantages of using polyethylene glycols are: they are chemically more reactive then fats; greated care is needed in processing to avoid inelegant contraction holes in the suppositories; the rate of release of water-soluble medications decreases with the increasing molecular weight of the polyethylene glycol; polyethylene glycols tend to be more irritating to mucous membranes than fats.
Aqueous polyethylene glycol solutions can be used either as suspending agents or to adjust the viscosity and consistency of other suspending vehicles. When used in conjunction with other emulsifiers, polyethylene glycols can act as emulsion stabilizers.
Liquid polyethylene glycols are used as water-miscible solvents for the contents of soft gelatin capsules. However, they may cause hardening of the capsule shell by preferential absorption of moisture from gelatin in the shell.
In concentrations up to approximately 30% v/v, PEG 300 and PEG 400 have been used as the vehicle for parenteral dosage forms.
In solid dosage formulations, higher molecular weight polyethylene glycols can enhance the effectiveness of tablet binders and impart plasticity to granules. However, they have only limited binding action when used alone, and can prolong disintegration if present in concentrations greater than 5% w/w. When used for thermoplastic granulations, a mixture of the powdered constituents with 10-15% w/w/ PEG 6000 is heated to 70-75 oC. The mass becomes paste-like and forms granules if stirred while cooling. This technique is useful for the preparation of dosage forms such as lozenges when prolonged disintegration is required.
Polytheylene 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.
In film coatings, solid grades of polyethylene glycol can be used alone for the film coating of tablets or can be useful as hydrophilic polishing materials. Solid grades are also widely used as plasticizers in conjunction with film forming polymers. The presence of polyethylene glycols, especially liquid grades, in film coats tends to increase their water permeability and may reduce protection against low pH in enteric coating films. Polyethylene glycols are useful as plasticizers in micro-encapsulated products to avoid rupture of the coating film when the microcapsules are compressed into tablets.
Polyethylene glycol grades with molecular weights of 6000 and above can be used as lubricants, particularly for soluble tablets. The lubricant action is not as good as that of magnesium stearate, and stickiness may develop if the material becomes too warm during compression. An antiadherent effect is also exerted, again subject to the avoidance of over-heating.
In addition, polyethylene glycols have been used in the preparation of urethane hydrogels which are used as controlled release agents.
STABILITY AND STORAGE CONDITIONS
Polyethylene glycols are chemically stable in air and in solution although grades with a molecular weight less than 2000 are hygroscopic. Polyethylene glycols do not support microbial growth, nor do they become rancid.
Polyethylene glycols and aqueous polyethylene glycol solutions can be sterilized by autoclaving, filtration or gamma irradiation. Sterilization of solid grades by dry heat at 150oC for one hour may induce oxidation, darkening and the formation of acidic degradation products. Ideally, sterilization should be carried out in an inert atmosphere. Oxidation of polyethylene glycols may also be inhibited by the inclusion of a suitable antioxidant.
If heated tanks are used to maintain solid polyethylene glycols in a molten state, care must be taken to avoid contamination with iron, which can lead to discoloration. The temperature must be kept to the minimum necessary to ensure fluidity; oxidation may occur if polyethylene glycols are exposed for long periods to temperatures exceeding 50oC. However, storage under nitrogen reduces the possibility of oxidation.
Polyethylene glycols should be stored in well-closed containers in a cool, dry place. Stainless steel, aluminum, glass or lined steel containers are preferred for the storage of liquid grades.
The chemical reactivity of polyethylene glycols is mainly confined to the two terminal hydroxyl groups, which can be either esterified or etherified. However, all grades can exhibit some oxidizing activity due to the presence of peroxide impurities and secondary products formed by autoxidation.
Liquid and solid polyethylene glycol grades may be incompatible with some colors.
The anitbacterial activity of certain antibiotics, particularly penicillin and bacitracin, is reduced in polyethylene glycol bases. The preservative efficacy of the parabens may also be impaired due to binding with polyethylene glycols.
Physical effects caused by polyethylene glycol bases include softening and liquefaction in mixtures with phenol, tannic acid and salicylic acid. Discoloration of sulfonamides and dithranol can also occur and sorbitol may be precipitated from mixtures. Plastics, such as polyethylene, phenol form aldehyde, polyvinyl chloride and cellulose-ester membranes (in filters) may be softened or dissolved by polyethylene glycols. Migration of polyethylene glycol can occur from tablet film coating, leading to interaction with core components.
Polyethylene glycols are widely used in a variety of pharmaceutical formulations. Generally, they are regarded as nontoxic and nonirritant materials. However, adverse reactions to polyethylene glycols have been reported and although of relatively low toxicity, any toxicity appears to be greatest with polyethylene glycols of low molecular weight.
Observe normal precautions appropriate to the circumstances and quantity of material handled. Eye protection is recommended.