Copolymers of methyl vinyl ether and maleic anhydride

2 COPOLYMERS OF METHYL VINYL ETHER AND MALEIC ANHYDRIDE 

To provide better control of polymer matrix erosion, a more orderly degradation and erosion process is needed. In an effort to achieve this goal, materials that erode heterogeneously have been produced. In particular, for materials that erode from the surface only, the kinetics of dissolution and the release of incorporated drugs can be precisely controlled. The first surface-eroding bio-erodible polymer formulation was produced at Alza Corp. in the 1970s it was a copolymer of methyl vinyl ether and maleic anhydride [20]  

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Because the urea-urease interaction leads to a pH increase, a polymer that increases erosion rate with increasing pH is needed. A useful polymer for this application is a partially esterified copolymer of methyl vinyl ether and maleic anhydride. This copolymer undergoes surface erosion with an erosion rate that is extraordinarily pH-dependent (J). The polymer dissolves by ionization of the carboxylic acid groups as shown below ... 

Figure 2. Hydrocortisone release rate at 35°C from a n-hexyl half-ester of a copolymer of methyl vinyl ether and maleic anhydride at pH 6.25 in the absence and presence of external urea. No external urea IC M external urea s10 M external urea. (Reproduced with permission from Ref. 2. Copyright 1979, American Pharmaceutical Association.)...

The first example of a surface eroding polymer was a partially esterified copolymer of methyl vinyl ether and maleic anhydride, published in 1978 [1], These polymers solubilize by ionization of carboxylic acid groups as shown in Scheme 1 and because at low pH the carboxyl groups are unionized and hence the polymer is insoluble, these materials are useful as enteric coatings to protect oral dosage forms from dissolution in the stomach [4-6]. 

The previous two sections reviewed characteristics of polymers that, in general, are not soluble in water and, therefore, are typically used as solid materials fibers, matrices, microspheres, or foams. Water-soluble polymers are also useful as biomaterials. Water-soluble polymers can be used in their molecular, water-soluble form as agents to modify other materials or as solid, dissolvable matrices (see the example of copolymers of methyl vinyl ether and maleic anhydride in Section A.2.2). Alternatively, water-soluble polymers may be cross-linked, by chemical or physical means, into solid materials (gels) that swell in water but do not dissolve. 

Synonyms 2,5-Furandione, polymerwith methoxyethene 2,5-Furandione, polymer with methoxyethylene Methyl vinyl ether/maleic anhydride copolymer Poly (maleic anhydride-methyl vinyl ether) Poly (methyl vinyl ether-alt-maleic anhydride) Poly(methyl vinyl ether/maleic anhydride) Polyvinyl methyl ether-maleic anhydride PVM/MA Definition Copolymer of methyl vinyl ether and maleic anhydride Empirical (C4H2O3 CsHsO),... 

Definition Copolymer of methyl vinyl ether and maleic anhydride Empirical (C4H2O3 C3HsO)x Formula [-CHzCHOCHaCHCOOCOCH-Jn Properties Wh. powd. sol. in water, oxygenated soivs. m.w. 20,000-67,000 anionic Toxicology Toxic cancer suspect agent TSCA iisted... 

Chem. Descrip. Copolymer of methyl vinyl ether and maleic anhydride Ionic Nature Anionic CAS 9011-16-9... 

Uses. Union Carbide consumes its vinyl ether production in the manufacture of glutaraldehyde [111-30-8J. BASF and GAF consume most of their production as monomers (see Vinyl polymers). In addition to the homopolymers, the copolymer of methyl vinyl ether with maleic anhydride is of particular interest. 

Several polymers were found to fit all or most of the above criteria and were used to prepare the carrier films. Many polymers have been used for this purpose, viz., ethyl cellulose, poly(y-benzyl glutamate), poly(vinyl acetate), cellulose acetate phthalate, and the copolymer of methyl vinyl ether with maleic anhydride. In addition to the base polymers, plasticizers were often needed to impart a suitable degree of flexibility. Plasticizers, which are found to be compatible with polymeric materials include, acetylated monoglycerides, esters of phthalic acid such as dibutyl tartarate, etc. An excipient was usually incorporated into the matrix of the carrier films. The excipients used were water-soluble materials, which are capable of creating channels in the polymer matrix and facilitate diffusion of the drug. PEGs of different molecular weights were used for this purpose. 

In a very recent publication, Bergbreiter, and co-workers studied the extension of this concept using the pH value as a regulatory variable [20 b]. A phosphine-modified polyacid (a copolymer from methyl vinyl ether and maleic acid anhydride, Gantrez ) was taken as a ligand for rhodium. The rate of hydrogenation of various unsaturated substrates was reversibly modified by tuning the pH value. 

An interesting example is the partial esters of a methyl vinyl ether and maleic anhydride copolymer (9., 11). 

In fact, the copolymers of methacrylic acid with maleic anhydride (14) and the copolymers of vinyl alcohol with maleic anhydride (127) obtained respectively from optically active (l-methyl-benzyl)-methacrylate or (l-methyl-benzyl)-vinyl-ether and maleic anhydride, were optically active, but their rotatory power was rather small. 

Poly(methyl vinyl ether-co-maleic anhydride) and their monoalkyl ester derivatives have been shown on rabbits to be neither primary irritants nor primary sensitizers to skin and eyes The acute oral toxicities on white rats of the two copolymers are, respectively, 29 g/kg and 25 g/kg body weight. 

MVE/MAN Copolymers. Various mol wt grades of poly(methyl vinyl ether-fo-maleic anhydride) (PMVEMA) are available from International Specialty Products, Inc. (formerly GAF Corp.), under the trade name of Gantrez. Table 6 illustrates the M. and MWD found for commercially available polymers. As can be seen, high molecular weights are readily achieved. 

Even though partially esterified copolymers of methyl vinyl ether-maleic anhydride copolymers were orignally designed to dissolve abruptly with an increase in external pH, in a constant pH environment they undergo a controlled dissolution process and are therefore useful materials for the controlled release of therapeutic agents dispersed within them (12),... 

Neutral and acidic polymers such as polyvinyl pyrrolidone, copolymers of polyvinyl pyrrolidone with vinyl acetate, and copolymers of methyl vinyl ether with half esters of maleic anhydride, are all used in hair styling and hair setting products. 

E. Moreno, J. Schwartz, E. Larraneta, P.A. Nguewa, C. Sanmartin, M. Agiieros, J.M. Irache, and S. Espuelas, Thermosensitive hydrogels of poly(methyl vinyl ether-co-maleic anhydride) - Pluronic F127 copolymers for controlled protein release, Int. J. Pharm., 459,1-9,2014. 

Copolymer of methyl vinyl ether Microencapsulation and maleic anhydride... 

As pointed out by Heller (2), polymer erosion can be controlled by the following three types of mechanisms (1) water-soluble polymers insolubilized by hydrolytically unstable cross-links (2) water-insoluble polymers solubilized by hydrolysis, ionization, or protonation of pendant groups (3) hydrophobic polymers solubilized by backbone cleavage to small water soluble molecules. These mechanisms represent extreme cases the actual erosion may occur by a combination of mechanisms. In addition to poly (lactic acid), poly (glycolic acid), and lactic/glycolic acid copolymers, other commonly used bioerodible/biodegradable polymers include polyorthoesters, polycaprolactone, polyaminoacids, polyanhydrides, and half esters of methyl vinyl ether-maleic anhydride copolymers (3). 

Figure 9 Relationship between pH of dissolution and size of ester group in half-esters of methyl vinyl ether-maleic anhydride copolymers. (Reproduced with permission from Ref.

Figure 10. Release of naltrexone from the n-hexyl half-ester of methyl vinyl ether-maleic anhydride copolymer at pH 7.4 and 37°C. Disks 5.5 x 0.75 mm naltrexone loading 10 wtj.

Fig. 5.3 The IR spectrum of methyl vinyl ether-maleic anhydride copolymer represented by different number of FCs and HCs. The original consists of 512 intensity values. After the transformation, the coefficients are truncated step by step as shown in Fig. 5.2 the number of the remaining coefficients is shown beside respective steps. The reduced representations are then transformed back to 512 intensity values and plotted.

TWO organometallic polymers previously developed, tributyl-tin methaczylate/methyl methacrylate copolymer (TBTM/MeM) and the tributyltin ester of methyl vinyl ether/maleic anhydride (TBT-MVEt-MAn), were selected for use as wood impregnants. Full Cell and Enpty Cell Methods were used to treat wood with TBTCVMeM in "Rule 66" mineral spirits and in combination with P13 creosote. Although the polymers seem to be miscible with the creosote, this combination results in only surface penetration of wood when... 

Figure 4, Rate of polymer dissolution and hydrocortisone release from n-butyl half-ester of methyl vinyl ether-maleic anhydride copolymer containing 10 wt% drug, (Reprinted with permission from Ref. 12. Copyright 1980, John Wiley ...

Neutral or negatively charged polymeric resins are commonly employed to provide styling benefits in products such as mousses, gels, hairsprays, and setting lotions. Typical examples in use today are the copolymer of vinyl acetate and cro-tonic acid, the copolymer of polyvinyl pyrrolidone and vinyl acetate (PVP/VA), the ethyl ester of the copolymer of polyvinyl methyl ether and maleic anhydride (PVM/MA), and the copolymer of octylacrylamide/acrylates/butylaminoethyl methacrylate (Amphomer). 

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