Ethylene oxide Specifications

Measurement of the humidity in the chamber and in the load has the least satisfactory technology of all the critical parameters of ethylene oxide sterilization. Direct measurement with gas chromatography or infrared analysis may not be reliable in the presence of ethylene oxide. Specification of the pressure increase obtained from steam injection is normally thought to be a satisfactory means of controlHng humidity, but it does not offer a monitoring option. 

Simplest examples are prepared by the cyclic oligomerization of ethylene oxide. They act as complexing agents which solubilize alkali metal ions in non-polar solvents, complex alkaline earth cations, transition metal cations and ammonium cations, e.g. 12—crown —4 is specific for the lithium cation. Used in phase-transfer chemistry. ... 

The various fumigants often exhibit considerable specificity toward insect pests, as shown in Table 8. The proper choice for any control operation is determined not only by the effectiveness of the gas but by cost safety to humans, animals, and plants flammabdity penetratabdity effect on seed germination and reactivity with furnishings. The fumigants may be used individually or in combination. Carbon tetrachloride has been incorporated with carbon disulfide, ethylene dichloride, or ethylene dibromide to decrease flammability, and carbon dioxide is used with ethylene oxide for the same purpose. 

Of the three worldwide manufacturers of poly(ethylene oxide) resins. Union Carbide Corp. offers the broadest range of products. The primary quaUty control measure for these resins is the concentrated aqueous solution viscosity, which is related to molecular weight. Specifications for Polyox are summarized in Table 4. Additional product specifications frequendy include moisture content, particle size distribution, and residual catalyst by-product level. 

Considerable interest has been shown ia poly(ethylene oxide) for diverse appHcations ia food, drug, and cosmetic products. Such uses fall within the scope of the Federal Food, Dmg, and Cosmetic Act. The U.S. FDA has recognized and approved the use of poly(ethylene oxide) for specific food and food packaging uses. USP/NF-grades of Polyox water-soluble resins (Union Carbide Corp.) are available for pharmaceutical appHcations. 

General recommendations for instmmentation include monitoring gas concentration, temperature, time, and the moisture content of the chamber. Hospital sterilizers are not usually equipped with instmmentation providing direct display of gas concentration and moisture content. These rely instead on a specific sequence of steps performed automatically and the recording of pressure which when 100% ethylene oxide is used is a perfect measure for the concentration of this gas. 

Ethoxylation of alkyl amine ethoxylates is an economical route to obtain the variety of properties required by numerous and sometimes smaH-volume industrial uses of cationic surfactants. Commercial amine ethoxylates shown in Tables 27 and 28 are derived from linear alkyl amines, ahphatic /-alkyl amines, and rosin (dehydroabietyl) amines. Despite the variety of chemical stmctures, the amine ethoxylates tend to have similar properties. In general, they are yellow or amber Hquids or yellowish low melting soHds. Specific gravity at room temperature ranges from 0.9 to 1.15, and they are soluble in acidic media. Higher ethoxylation promotes solubiUty in neutral and alkaline media. The lower ethoxylates form insoluble salts with fatty acids and other anionic surfactants. Salts of higher ethoxylates are soluble, however. Oil solubiUty decreases with increasing ethylene oxide content but many ethoxylates with a fairly even hydrophilic—hydrophobic balance show appreciable oil solubiUty and are used as solutes in the oil phase. 

Emulsion polymerizations of vinyl acetate in the presence of ethylene oxide- or propylene oxide-based surfactants and protective coUoids also are characterized by the formation of graft copolymers of vinyl acetate on these materials. This was also observed in mixed systems of hydroxyethyl cellulose and nonylphenol ethoxylates. The oxyethylene chain groups supply the specific site of transfer (111). The concentration of insoluble (grafted) polymer decreases with increase in surfactant ratio, and (max) is observed at an ethoxylation degree of 8 (112). 

Several cleaning formulations for specific uses contain unreacted polyamines. Examples include mixtures of ammonium alkylbenzenesulfonate, solvents, and PIP which give good cleaning and shine performance on mirrors and other hard surfaces without rinsing (305), and a hard-surface cleaner composed of a water-soluble vinyl acetate—vinyl alcohol copolymer, EDA, cyclohexanone [108-94-1] dimethyl sulfoxide [67-68-5] a surfactant, and water (306). TEPA, to which an average of 17 moles of ethylene oxide are added, improves the clay sod removal and sod antiredeposition properties of certain hquid laundry detergents (307). 

Elastomer ECH, % Chlorine, % Ethylene oxide, % CAS Registry Number Specific gravity ml T,°C... 

Ethylene oxide is sold as a high purity chemical, with typical specifications shown ia Table 14. This purity is so high that only impurities are specified. There is normally no assay specification. Proper sampling techniques are critical to avoid personal exposure and prevent contamination of the sample with trace levels of water. A complete review and description of analytical methods for pure ethylene oxide is given ia Reference 228. 

Specific Volume of Gases Formed on Explosion. 723ml/g (NG 712ml) (Ref 46) Stabilization. Chromatographically pure Mannitol Hexanitrate was mixed with varying percentages of 22 stabilizers and the mixts tested for stability in the 100° heat test best results were obtained with a mixt of 96% MHN, 2% Amm oxalate, and 2% dicyandiamide (4.07% wt loss after 48 hours, 5.74% after 96 hours) (Ref 56). The use of ethylene oxide as a stabilizer is reported in Ref 27 Thermal Decomposition. Slow heating causes decompn at 150° with evolution of red fumes (Ref 20, p 249)... 

A useful way of classifying chemicals is shown in Fig. 2.1. Chemicals are divided on the basis of volume and character. Bulk chemicals, or commodities, are produced in large quantities and sold on the basis of an industry specification. There is essentially no difference in the product from different suppliers. Typical examples would be acetone, ethylene oxide, and phenol. Pseudo commodities are also made in large quantities but are sold on the basis of their performance. In many cases the product is formulated and properties can differ from one supplier to another. Examples include large volume polymers, surfactants, paints, etc. 

The sterilization processes described in the Ph Eur are preferred, especially terminal sterilization in the final container alternative processes have to be justified. All sterilization processes will need to be described and appropriate in-process controls and limits included. Where Ph Eur prescriptions are followed, there should be a statement to this effect in the application. Most of this information should be discussed in the development pharmaceutics section. Reference is made to the specific guidelines on ethylene oxide sterilization and irradiation sterilization, which are discussed further below. The possibility of parametric release for terminal processes such as saturated steam and irradiation is mentioned (see below). For all sterile products there should be a sterility requirement included in the finished product specification regardless of the outcome of validation studies. 

Where toxic gases or solvents have been used in the manufacturing process, validation data on their removal and relevant release and shelf life specifications and acceptance limits should be included in the dossier (taking into account the ICH guidelines on residual solvents and the CPMP guideline on ethylene oxide usage). These can be discussed in the development pharmaceutics section or elsewhere. 

In addition to the general guidelines on sterilization issues, there are two specific guidelines on the use of ethylene oxide sterilization (3AQ3a, adopted in 1994)... 

The catalyst consists of silver supported on alumina and, while it is reasonably specific, appreciable amounts of C02 and H20 are also formed. Over the range of interest, the yield of ethylene oxide is relatively constant so that for present purposes, we may regard the reaction stoichiometry as... 

Gerin M, Tardif R, Brodeur J. 1988. Determination of specific urinary thioethers derived from acrylonitrile and ethylene oxide. IARC Sci Pub 275-278. 

Specific design considerations for a few substances including acrylic acid, styrene, organic peroxides, ethylene oxide, and 1,3-butadiene are given in CCPS (1995) on the basis of an industiy-practice survey. Detailed information for other substances is distributed by industry... 

The starting solution contained 1.0 mol/liter of ethylene oxide, 55 mol/liter of water and 0.9 wt% of acid. Neglect any changes in water concentration and find the pseudo first order specific rate. 

Ethoxylated alkyl amines in pesticide formulations were separated using two different columns a cyano-modified silica column to determine the alkyl distribution and an amino-modified column to determine the ethylene oxide distribution [88]. The detection, specific for ethoxylated amine, was performed with a post-column ion-pair extraction system and fluorescence detection. 

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