Impurities vinyl chloride monomer process

Presence of impurities in excipients can have a dramatic influence on the safety, efficacy or stability of the drug product. Monomers or metal catalysts used during a polymerization process are toxic and can also destabilize the drug product if present in trace amounts. Due to safety concerns, the limit of vinyl chloride (monomer) in polyvinyl pyrrolidone is nmt 10 ppm, and for hydrazine (a side product of polymerization reaction) nmt 1 ppm. Monomeric ethylene oxide is highly toxic and can be present in ethoxylated excipients such as PEGs, ethoxylated fatty acids, etc. 

Transfer to monomer is an important process in the radical polymerization of vinyl chloride so that the number of initiator fragment in a polymer chain is less than unity. For example, poly(vinyl chloride)s prepared with AIBN in 1,2-dichloroethane at 40°C were found to contain 0.17 0.34 AIBN fragments per chain from the 13C NMR analysis of the polymer reduced with Bu3SnH. The polymers also contained a CN group in the chain (0.025 0.12 per chain), suggesting the copolymerization of methacrylonitrile which was formed in situ or admitted as an impurity in the starting AIBN.79... 

Polymers contain various elements, metallic and nonmetallic. Some elements are a constituent part of the monomers, such as nitrogen in acrylonitrile or chlorine in poly(vinyl chloride), while other elements occur as impurities or are part of some additives (e.g., zinc stearate). Their concentrations range from a (tg per kg level to several percent. Analysis of the element content is especially important for manufacturing process control. Elements can be determined after chemical or physical destruction of polymer, or directly by nondestructive methods. 

Some peculiarities of the thermal and thermooxidative decomposition of polyvinyl chloride depend on the conditions of its production. Thus, it is known that samples of the polymer produced by initiating the polymerization of vinyl chloride with ultraviolet irradiation possess higher stability in comparison with samples produced in polymerization under the action of chemical agents [26, 27]. Reversibility of the process of dehydrochlorination in the decomposition of samples of polyvinyl chloride produced by the latex method is noted, while in the process of decomposition of suspension polymer, the phenomenon of reversibilily is not observed [21]. It has been shown that the rate of dehydrochlorination of the latex polymer is significantly higher than that of the suspension polymer under the same conditions [21]. It has been established that the polymerization of vinyl chloride in the presence of oxygen leads to the formation of unstable peroxide groups, which can initiate decomposition of the polymer [28, 29]. It is noted that an extremely substantial influence on the stability of polyvinyl chloride is exerted by the purity of the monomer, as well as the presence of impurities of metals of variable valence [28]. 

Copolymersof vinyl chloride with vinylidine chloride, produced by the suspension method, are more stable than the latex copolymers. The rates of thermal decomposition of polyvinyl chloride and the copolymer of vinyl chloride with vinylidine chloride, produced by the latex method, are practically the same for the latex copolymer, just as for the latex homopolymer, reversibility of the process of dehydrochlorination is observed [21]. In an investigation of the stability of copolymers of vinyl chloride with vinyl acetate, vinylidine chloride, and with vinylisobutyl ether in nucleophilic substitution reactions, it was found that the copolymer with vinyl acetate is the least stable to the action of alcoholic alkali the copolymers with vinylidine chloride and vinylisobutyl ether proved more stable [56]. The stability of the copolymer of vinyl chloride witii methyl acrylate is substantially increased when the degree of homogeneity of the copolymer with respect to composition is increased, and when monomers with a smaller content of impurities are used, as well as when the copolymerization is conducted in the presence of chain carriers [57, 58]. 

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