Strongly swellable, moderately crosslinked copolymers of vinylpyrrolidone and vinyl acetate

Strongly swellable, moderately crosslinked poly(vinyl pyrrolidone/vinyl acetate) copolymer (XL-PVP/VA) in the form of fine, white powders characterized by (a) an aqueous gel volume of about 15 to 150 ml/g of polymer, (b) a Brookfield viscosity in 5% aqueous solution of at least about 10,000 cps, and (c) being prepared directly by precipitation polymerization of VP and VA monomers in the presence of a crosslinking agent in the amount of about 0.1 to about 2% by weight of VP and VA.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
This invention relates to crosslinked copolymers of vinylpyrrolidone (VP) 
and vinyl acetate (VA), referred to herein as "XL-PVP/VA", and more 
particularly, to strongly swellable, moderately crosslinked PVP/VA 
copolymers which are prepared directly as fine, white powders by 
precipitation polymerization of vinylpyrrolidone and vinyl acetate in an 
organic solvent. 
2. Description of the Prior Art 
Strongly swellable, moderately crosslinked polyvinylpyrrolidone (XL-PVP) 
was made by Shih, J., et al. in U.S. Pat. No. 5,073,614 by precipitation 
homopolymerization of VP in an organic solvent such as cyclohexane or 
heptane. However, it is desired to provide new and improved crosslinked 
polymers which are less hygroscopic and which exhibit enhanced mechanical 
properties, as compared to XL-PVP itself. 
Accordingly, it is an object of this invention to provide a suitable 
process for making strongly swellable, moderately crosslinked copolymers 
of vinylpyrrolidone and vinyl acetate which are substantially 
non-hygroscopic and which have advantageous mechanical properties. 
These and other objects of the invention will be made apparent from the 
following description of the invention. 
SUMMARY OF THE INVENTION 
What is provided herein is a process for making strongly swellable, 
moderately crosslinked copolymers of VP and VA, in a defined weight ratio, 
preferably about 90/10 to about 60/40, in the form of fine, white powders 
having (a) an aqueous gel volume of about 15 to 150 ml/g of copolymer, 
preferably about 50 ml/g, (b) a Brookfield viscosity in 5% aqueous 
solution of at least about 10,000 cps, preferably about 20,000 to about 
50,000 cps, and (c) being prepared by precipitation polymerization of VP 
and VA monomers in an organic solvent, preferably heptane, hexane or 
cyclohexane, with a free radical polymerization initiator, suitably about 
0.2-5%, in the presence of a crosslinker, in an amount of about 0.1 to 
about 2% by weight of the monomers, while maintaining the overall monomer 
concentration at less than about 15% by weight, and feeding the monomers 
at a feeding rate of less than about 0.2 ml/min for 0.5 l of solvent, 
preferably 0.1-0.15 ml/min, and while agitating the reaction mixture at 
greater than about 300 rpm, preferably 400-500 rpm. 
In the preferred embodiment of the invention, (a) is 25 to 75 ml/g of 
copolymer, (b) is at least 15,000 cps, and (c) provides a terpolymer 
having a T.sub.g of at least 150.degree. C., preferably 150.degree. to 
about 180.degree. C. The initiator level preferably is about 0.25 to 0.8%. 
In an optimum form of the invention, (a) is 30 to 60 ml/g, (b) is about 
20,000 to 50,000 cps, and (c) T.sub.g is 150.degree. C. to 160.degree. C., 
and the initiator level is about 0.35 to 0.6%. 
Gel volume is a measure of the swelling property of the crosslinked polymer 
and is defined as the equilibrium aqueous swelling volume of polymer per 
unit weight, and is expressed in the units of ml/g. Gel volume is 
determined by first adding 1 g. of the polymer to a suitable graduated 
cylinder filled with water. This mixture then is shaken and allowed to 
stand at room temperature for 3 days. The volume of the gel which is 
produced in water is measured and taken as the gel volume. Similarly, the 
gel volume concept can be applied to non-aqueous systems. 
The fine, white powder polymers of the invention are prepared directly by a 
precipitation polymerization process in an organic solvent, such as an 
aliphatic hydrocarbon solvent, preferably cyclohexane or heptane, or an 
aromatic hydrocarbon, such as toluene, in the presence of about 0.1 to 2% 
by weight of monomers of a crosslinking agent, suitably 
N,N'-divinylimidazolidone, 1-vinyl-3(E)-ethylidene pyrrolidone, 
triallyl-1,3,5-triazine-2,4,6(1H,3H,5H)-trione, 
2,4,6-triallyloxy-1,3,5-triazine, and pentaerythritol triallyl ether, at 
about 5 to 25% solids.

DETAILED DESCRIPTION OF THE INVENTION 
In accordance with the invention, strongly swellable, moderately 
crosslinked PVP/VA copolymers are prepared directly in the form of fine, 
white powders by precipitation polymerization of vinyl pyrrolidone and 
vinyl acetate in the presence of a predetermined amount of a crosslinking 
agent and a free radical polymerization initiator in an organic solvent, 
preferably an aliphatic hydrocarbon, e.g. a C.sub.3 -C.sub.10 saturated, 
branched or unbranched, cyclic or acyclic aliphatic hydrocarbon, and most 
preferably cyclohexane or heptane, or mixtures thereof. 
The amount of solvent used in the process of the invention should be 
sufficient to dissolve an appreciable amount of the reactants and to 
maintain the copolymer precipitate in a stirrable state at the end of the 
polymerization. Generally, about 5 to 25% solids, preferably 10-20%, is 
maintained in the reaction mixture. 
The precipitation polymerization process of the invention is carried out in 
the presence of a suitable free radical polymerization initiator. Suitable 
initiators include acyl peroxides such as diacetyl peroxide, dibenzoyl 
peroxide and dilauryl peroxide; peresters such as t-butylperoxy pivalate, 
tert-butyl peroxy-2-ethylhexanoate; peroxides such as di-tert-butyl 
peroxide; percarbonates such as dicyclohexyl peroxydicarbonate; and azo 
compounds such as 2,2'-azobis(isobutyronitrile), 
2,2'-azobis(2,4-dimethylvaleronitrile), 1,1'-azobis(cyanocyclohexane), and 
2,2'-azobis(methylbutyronitrile). Other initiators known in the art also 
may be used. A preferred initiator is the following: 
______________________________________ 
Preferred 
Initiator 
______________________________________ 
t-Butyl peroxy- 
Atochem N.A. Liquid; 
75% active 
pivalate (Lupersol 11) in mineral 
spirits 
______________________________________ 
The amount of such initiator may vary widely; generally about 0.2-5.0% is 
used, based on the weight of total monomers charged. 
The reaction temperature may vary widely; generally the reaction mixture is 
maintained at about 40.degree.-150.degree. C., preferably 
60.degree.-70.degree. C., during the polymerization. Pressure usually is 
kept at atmospheric pressure, although higher and lower pressures may be 
used as well. 
In order to make a highly purified crosslinked copolymer, the introduction 
of another initiator at a higher operational temperature is desirable 
since it effectively reduces the amount of residual VP and VA monomer 
content to below 100 ppm in the product. The hihger temperature initiator 
can be added to the system separately or in admixture with the low 
temperature initiator. The preferred higher temperature initiator is 
2,5-dimethyl-2,5-di(tert-butylperoxy) hexane (Lupersol.RTM. 101). The 
amount of such initiator may be about 0.2-5.0%, based on the weight of 
total monomers charged. The higher temperature reaction is usually at 
between about 110.degree. C. and 150.degree. C., preferably at between 
120.degree. C. and about 135.degree. C. 
The reaction mixture should be stirred vigorously under an inert 
atmosphere, e.g. nitrogen, during the polymerization. A stirring rate of 
about 300-600 rpm in 1-liter lab reactor is sufficient to effect the 
desired polymerization and to keep the precipitate in a stirrable state 
during the polymerization. 
Suitable crosslinking agents for use in the invention include such 
multifunctional compounds as the divinyl ethers of an aliphatic diol, e.g. 
the divinyl ethers of 1,3-propanediol, 1,4-butanediol, 1,5-pentanediol, 
1,6-hexanediol, 1,7-heptanediol, 1,8-octanediol, 1,9-nonanediol, 
1,10-decanediol, 1,11-unidecanediol, and 1,12-dodecanediol; as well as the 
divinyl ethers of diethylene glycol, triethylene glycol, tetraethylene 
glycol, pentaethylene glycol, hexaethylene glycol, heptaethylene glycol, 
octaethylene glycol, nonaethylene glycol, decaethylene glycol and further 
polyalkylene glycols up to a molecular weight of about 6000. Other 
suitable crosslinking agents include 1,7-octadiene, 1,9-decadiene, 
1,13-tetradecadiene, divinylbenzene, N-N'-divinylimidazolidone, 
1-vinyl-3(E)-ethylidene pyrrolidone and methylene bisacrylamide; acrylates 
such as polyethylene glycol diacrylate, trimethylolpropane triacrylate, 
propylene glycol diacrylate; allyl ether derivatives of polyhydric 
alcohols such as pentaerythritol triallyl ether; or polyhydric alcohols 
esterified once or twice with acrylic acid; triallylamine, 
tetraallylethylenediamine, diallyl phthalate, and the like. Preferred 
crosslinking agents are the following: N,N'-divinylimidazolidone, 
pentaerythritol triallyl ether, 1-vinyl-3(E)-ethylidene pyrrolidone, 
triallyl-1,3,5-triazine-2,4,6(1H,3H,5H)-trione, and 
2,4,6-triallyloxy-1,3,5-triazine. 
The precipitation polymerization process of the invention may be carried 
out by first precharging a suitable reactor with a predetermined amount of 
the organic solvent, for example, an aliphatic hydrocarbon solvent, and 
heating the solvent to a desired reaction temperature while stirring 
vigorously under an inert gas atmosphere. The initiator is then charged 
into the reactor. 
Then the vinylpyrrolidone and vinyl acetate monomers, and the crosslinker 
material are admitted into the reactor continuously through syringe pumps. 
The amounts and ratios of monomers and crosslinker can be adjusted based 
on a predetermined vinylpyrrolidone and vinyl acetate ratio in the 
copolymer and the extent of crosslinking desired in the final product. 
Since vinylpyrrolidone is much more reactive than vinyl acetate during the 
copolymerization, and it is desired to provide substantially uniform 
copolymer relative to the distribution of monomer units on the 
macromolecular backbone, the vinyl acetate addition time is made shorter, 
usually 3-5 hours, and the vinylpyrrolidone and crosslinker material 
addition time is made longer, usually 5-7 hours. Preferably, the reactants 
are admitted into the reactor below the surface of the solvent. The 
reaction mixture is held for an additional period of time, usually 6-8 
hours, at a higher temperature, with the addition of a high temperature 
initiator, e.g. 2,5-dimethyl-2,5-di(tert-butylperoxy) hexane 
(Lupersol.RTM. 101), to complete the polymerization. 
Finally, the mixture is cooled to room temperature. Filtering, washing with 
solvent, and drying provides the desired polymer in yields approaching 
quantitative. Alternatively, the reaction product may be dried directly to 
provide the polymer powders. 
The polymerization process of the invention in cyclohexane or heptane 
solvent provides the desired PVP/VA polymer product as a fine, white 
powder, which precipitates readily, in quantitative yield, with 
substantially the same degree of crosslinking as the charge of VP and VA 
monomers and crosslinking agent, in a smooth polymerization without 
excessive swelling of polymer during the course of the process. More 
particularly, the solvents of the invention are non-solvents for PVP and 
VA monomers, which enable the polymerization to proceed in the presence of 
the crosslinking agent without excessive build-up of viscosity of the 
reaction mixture during polymerization. 
In order to provide for easy removability from the reactor, the PVP/VA 
copolymer product of the invention preferably should not swell in the 
hydrocarbon solvent during preparation. To determine the maximum allowable 
monomer concentration in the solvent without causing the polymer to swell, 
a series of solubility tests were carried out as follows. PVP/VA copolymer 
powders were added to heptane in the presence of a certain amount of VP 
and VA. The results are shown below: 
Solubility Test of PVP/VA in Heptane in the presence of VP and VA 
Sample: Non-XL PVP/VA (VP/VA=60/40 by weight). 
1 g. of sample in 10 g heptane was set at room temperature overnight. 
______________________________________ 
Amt of VP and 
VA (1:1 by wt) 
% VP and VA Observation 
______________________________________ 
0 0% All powders settled down, 
none swollen. 
0.2 g 2% Some of the powders were 
swollen. 
0.3 g 3% All of the powders were 
swollen. 
0.4 g 4% All of the powders were 
swollen. 
0.5 g 5% All of the powders were 
swollen. 
1.0 g 10% Some of the polyner 
dissolved, some swollen. 
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The above results indicated that when the VP and VA concentration in the 
PVP/VA copolymer is 2% or higher, PVP/VA was swollen in heptane. 
Therefore, during the preparation of crosslinked PVP/VA, the monomer 
concentration should be maintained at a very low level (preferably below 
3%) to keep the product from swelling in the solvent or forming a gum. 
Several measures were taken to achieve the desired low monomer level during 
the polymerization process: (1) maintaining a low overall monomer 
concentration (no higher than 15% by weight), (2) providing a low monomer 
feeding rate (no higher than 0.2 ml per minute for 500 g of solvent), 
and/or (3) very rapid agitation of the reactants (no lower than 300 rpm). 
The invention will be illustrated by reference to the following examples, 
which are given in parts by weight unless otherwise specified. 
EXAMPLE 1 
A 1-l, 4-necked glass reaction vessel was equipped with two syringe pumps, 
controlled by computer, for continuous addition of monomers (VP and VA), 
and crosslinker, a constant speed mechanical stirrer set at 300 rpm, an 
adaptor for admitting nitrogen, and a thermocouple connected to a 
temperature controller. The vessel was charged with 500 g of heptane. 
Nitrogen was started to purge through the reactor. The temperature was 
raised to 65.degree. C. and held for 30 minutes. Then 220 microliter (190 
micrograms) of t-butylperoxy pivalate (Lupersol 11) was added through the 
syringe. Thereafter Feeds 1 and 2 were introduced through the syringe 
pumps simultaneously. Feed 1 was a mixture of 67.5 g of vinylpyrrolidone 
and 0.34 g (0.45% of VP and VA comonomers by weight) of 
triallyl-1,3,5-triazine-2,4,6(1H,3H,5H)-trione (TATT), and it was 
introduced into the reactor over a period of 6 hours. Feed 2 contained 
7.50 g of vinyl acetate and it was added over 4 hours. Then the reaction 
mixture was held at 65.degree. C. for another hour. 
Thereafter the mixture was cooled and transferred to a 1-l, high pressure 
Buchi reactor and 0.375 g of 2,5-dimethyl-2,6-di-(t-butylperoxy) hexane 
(Lupersol 101) was added through a syringe pump. Then the reactor was 
sealed, heated to 130.degree. C. and held for 7 hours. 
The mixture was cooled to room temperature, discharged and dried in a 
vacuum oven at 70.degree. C. for 1 day and 100.degree. C. for a second 
day. A blender was used to break the product into fine powders. 
A quantitative yield of crosslinked PVP/VA copolymer having a VP to VA 
ratio (w/w) of 90/10 and containing about 0.45% of the crosslinking agent 
was obtained. 
EXAMPLES 2-5 
The procedure of Example 1 was followed in Examples 2-5 using various 
amounts of VP and VA and different crosslinkers. 
A summary of the reaction mixtures used in Examples 1-5 is given in Table 1 
below. 
TABLE I 
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Ex. No. 
VP (g) VA (g) VP/VA (w/w) 
Crosslinker (g) 
______________________________________ 
1 67.5 7.5 90/10 TATT 0.34 
2 67.5 7.5 90/10 PTE 0.34 
3 60 15 80/20 PTE 0.34 
4 52.5 22.5 70/30 PTE 0.34 
5 45 30 60/40 PTE 0.34 
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PTE = Pentaerythritoltriallylether 
Properties of Copolymer of Invention 
The strongly swellable, moderately crosslinked PVP/VA copolymer powders of 
the invention are characterized by its unique gel volume and viscosity, 
which properties enable the polymer to thicken aqueous and non-aqueous 
solutions effectively. 
The viscosity of the polymer is defined by its Brookfield viscosity in cps, 
which is determined upon a 5% aqueous solution of the polymer at 
25.degree. C. by a standard analytical procedure using Model LTV and 
Spindle No. 4. 
For maximum utility, it is desirable that the hydrated polymer exhibit a 
high gel volume and a high viscosity. With increasing crosslinking density 
in the polymer, the gel volume decreases and viscosity increases and then 
decreases, passing through a maximum. In the crosslinked polymer system of 
this invention, an effective thickener product is provided by including 
crosslinker in the reaction mixture at a suitable concentration of about 
0.2 to 1.0% by weight, based upon VP and VA monomers, preferably about 
0.25 to 0.8%, and optimally, at about 0.35 to 0.6%. At this suitable 
amount of crosslinker loading, the crosslinked polymer product exhibits a 
gel volume of about 15 to 150 ml/g of polymer and a Brookfield viscosity 
of at least 10,000 cps. At the preferred crosslinker concentration, the 
gel volume is about 25 to 75 ml/g of polymer and its Brookfield viscosity 
is at least 15,000 cps. At the optimal amount crosslinker present in the 
reaction mixture, the polymer exhibits a gel volume of about 30 to 60 ml/g 
of polymer and a Brookfield viscosity of about 20,000 to 50,000 cps. 
Glass Transition Temperature (T.sub.g) 
The glass transition temperature, Tg, is an indicator of the extent of 
crosslinking in the copolymer. Above this temperature, the polymer is in 
viscous or rubbery state; below this temperature, it is in a hard or 
glassy state. T.sub.g is related to the amount of free ends in the 
polymer. If a polymer is completely crosslinked, it will be decomposed at 
an elevated temperature and no T.sub.g exists. If a polymer is moderately 
crosslinked, the T.sub.g can be determined and it should be higher than a 
non-crosslinked polymer with the same VP and VA composition. The XL-PVP/VA 
products of Examples 1-5 gave T.sub.g 's higher than corresponding non-XL 
PVP/VA which indicates a moderate crosslinking state in these copolymers. 
At an optimal amount of crosslinker in the reaction mixture, the T.sub.g 
of the crosslinked copolymer obtained is at least 150.degree. C., 
preferably in the range of 150.degree. C. to 180.degree. C., and 
optimally, at about 150.degree. C. to about 170.degree. C. 
The properties of the crosslinked PVP/VA copolymers herein with different 
VP to VA ratios, (Examples 1 to 5) including swell volume, Brookfield 
viscosity and glass transition temperature, are given in Table 2 below, in 
favorable comparison to non-crosslinked copolymers of the same 
composition. 
TABLE 2 
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Swell Brookfield 
T.sub.g, .degree.C. 
T.sub.g, .degree.C. 
Ex. No. 
VP/VA 
Volume, ml 
Viscosity, cps 
XL Copolymer 
non-XL Copolymer 
__________________________________________________________________________ 
1 90/10 
52 62,800 cps 
159 137 
2 90/10 
53 11,000 cps 
159 137 
3 80/20 
50 48,200 cps 
151 122 
4 70/30 
42 12,100 cps 
169 110 
5 60/40 
85 150,000 cps 
154 100 
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As an added feature of the invention, the residual VP and VA monomer 
content of the polymers obtained herein is less than about 0.1% by weight. 
In aqueous based processes, in contrast, the formation of a gel mass 
during polymerization may trap considerable amounts of VP and VA monomer 
in the polymeric gel network. 
The strongly swellable, moderately crosslinked PVP/VA copolymers of the 
invention are useful in pharmaceutical applications, such as in controlled 
release tablets, binders, coatings, nasal spray delivery systems, and 
tablet disintegrating agents; in personal care compositions, as for 
example, in hair conditioners and as a gelling agent in a gelled acidizer 
compositions. In these and other formulations and compositions, the 
substantially non-hygroscopic and predetermined hydrophilic/hydrophobic 
properties of the copolymer are useful in providing an improved swelling 
and thickening agent therein. 
The copolymers of the invention also find use as a disposable and extended 
wear soft and hard contact lenses by providing a material which has a high 
water content, excellent tensile strength, tear resistance and low 
affinity for lachrymal proteins and other contaminants. Other monomers 
such as methyl methacrylate and hydroxyethyl methacrylate may be included 
therein. 
While the invention has been described with particular reference to certain 
embodiments thereof, it will be understood that changes and modifications 
may be made which are within the skill of the art. Accordingly, it is 
intended to be bound only by the following claims, in which: