Aqueous coating dispersions

Aqueous dispersions of a water-swellable but water-insoluble polymer formed between a quaternary ammonium monomer and a nonionic monomer; methods for making such dispersions by dispersing said copolymers, in the form of a powder, in water; methods for coating pharmaceutical cores, powders, or granules with such dispersions; and coated pharmaceutical products made by such methods.

The present invention relates to film-forming aqueous dispersions of 
coating and binder agents, to methods for making such dispersions, and to 
the use of such dispersions for coating pharmaceutical dosage forms, for 
the granulation of pharmaceutically active powders, and for the production 
of pharmaceutical films. 
Aqueous coating dispersions for pharmaceutical dosage forms are known from 
published German patent application DOS No. 32 08 791 (corresponding to 
European patent publication No. 88,951). Such dispersions are prepared by 
reemulsifying a powdered emulsion polymer containing acid or basic groups 
in a water phase in which a small portion of the acid or basic groups is 
converted to the salt form by means of a base or an acid. By such a 
process, the original latex particles are isolated and, by salt formation 
on their surface, are hydrated and stably dispersed. Because of the 
content of acid or basic groups of the coating agent, the solubility or 
permeability to digestive fluids of the coatings produced therefrom on 
pharmaceutical dosage forms depends on the pH value of those fluids. This 
pH dependence may be desirable or undesirable, depending on the intended 
mode of action of the drug. 
Coatings for pharmaceutical dosage forms having a permeability for 
dissolved active ingredients that is independent of the pH value of the 
surrounding aqueous medium can be produced from the dragee coating 
compositions described in German patent No. 1,617,751. These compositions 
contain a copolymer having quaternary ammonium salt groups and are 
dissolved in organic solvents such as alcohols, ketones, or esters. 
Because of their content of quaternary ammonium groups, it is not possible 
to produce such polymers by emulsion polymerization and to prepare a 
redispersible powder therefrom. 
The object of the invention is to provide an aqueous coating dispersion for 
pharmaceutical dosage forms which forms a film upon drying and which gives 
water insoluble coatings having a diffusion permeability that is 
independent of the pH value of the surrounding medium. 
It has been found that such a dispersion can be prepared by dispersing a 
powdered coating agent in an aqueous phase with stirring if the powdered 
coating agent being dispersed in the aqueous phase is a copolymer, capable 
of swelling in water but not soluble therein, of a monoethylenically 
unsaturated quaternary ammonium compound capable of free-radical 
polymerization and of at least one nonionic monoethylenically unsaturated 
comonomer capable of free-radical polymerization and forming a water 
insoluble homopolymer. 
Typical dispersions of this type contain from 60 to 85 percent, based on 
their total weight, of an aqueous phase and from 40 to 15 percent by 
weight of a copolymer dispersed therein, said copolymer comprising from 5 
to 20 percent, by weight of the copolymer, of said quaternary ammonium 
compound, from 95 to 70 percent of said nonionic comonomer, and, 
optionally, up to 20 percent of other unsaturated comonomers which are 
copolymerizable with said monomers. 
The new coating dispersions contain no volatile combustible components and 
therefore can be dried without posing a fire or explosion hazard and 
without polluting the exhausted air with impurities, apart from water 
vapor, to form clear films as good as the coatings produced by organic 
solutions of the same copolymers. The films are insoluble in water at all 
pH values in the physiological range but are capable of swelling in water 
to the extent that water and pharmaceutically active substances dissolved 
therein are able to diffuse through them. Like the swelling capacity, the 
diffusion permeability of the films is independent of the pH value unless 
the solubility or diffusibility of the active substance itself varies with 
the pH value. The pH-independent permeability is due both to the 
quaternary ammonium salt groups, which, being salts of a strong base, are 
completely dissociated throughout the physiological pH range, and to the 
absence of other ionic groups whose pH-dependent dissociation would result 
in a pH-dependent diffusion permeability. 
The new dispersions thus are suitable for the production of delayed action 
pharmaceutical preparations which release the enclosed active substance at 
the same diffusion rate, regardless of the prevailing pH value, in each 
region of the digestive tract during passage therethrough and, after 
having been completely extracted, are eliminated without decomposing. Such 
polymer films may form an envelope over a tablet, a dragee, a capsule, a 
particle of an active substance, or the matrix for a granulation, or a 
matrix table compressed therefrom, or may contain the active substance 
embedded in the polymer film. The envelope may have a thickness from 10 to 
50 microns and, if desired, may form one layer of a multilayer coating. 
The production of coating films, coated pharmaceutical dosage forms, or 
granulations may be effected in the same manner as with other known 
aqueous coating dispersions. These are frequently modified prior to use 
with fillers or pigments such as talc or titanium dioxide, with 
plasticizers, and, if indicated, with odor- or taste-making additives. 
A special advantage is that by mixing two dispersions containing different 
amounts of quaternary ammonium groups the processor of the coating 
dispersions is able to obtain any desired permeability, and hence release 
rate, between the limits applicable when the two components are used 
alone. Since even minor differences in the composition of the copolymers 
result in pronounced differences in the release rate, a broad range of 
delayed actions can be obtained just by mixing. For example, a coating 
produced from a copolymer of ethyl acrylate, methyl methacrylate, and 
methacryloxyethyltrimethylammonium chloride in a weight ratio of 60:35:10 
applied to the paper membrane of a diffusion cell for measuring purposes, 
allowed 10.5 parts of phenylpropanolamine hydrochloride to diffuse through 
it over a period of five hours, whereas an otherwise identical coating 
produced from a copolymer with a weight ratio of 65:35:5 of the same 
monomer constituents resulted in the diffusion of only 1.2 parts of said 
active substance under the same conditions. Mixtures of the two 
dispersions, under the same test conditions gave diffusion values lying 
between the two extremes. The accompanying FIGURE shows the diffusion 
pattern over a five hour period. The good controllability of the diffusion 
rate and the substantially linear diffusion rate with each selected 
composition of the diffusion layer are apparent from the drawing. The 
coatings of pharmaceutical dosage forms behave similarly. 
The nature, and particularly the amount, of the quaternary ammonium 
compound present in the copolymeric agent are important factors affecting 
diffusion behavior. N-vinylpyridinium salts are suitable polymerizable 
quaternary ammonium compounds, for example. Quaternary aminoalkyl esters 
or aminoalkylamides of acrylic or methacrylic acid are preferred. These 
correspond to the general formula 
##STR1## 
wherein R is hydrogen or methyl; 
A is oxygen or NH; 
B is a linear or branched alkyl or is an alicyclic hydrocarbon, and more 
particularly has from 2 to 8 carbon atoms; 
R.sub.1, R.sub.2, and R.sub.3, taken alone, are the same or different alkyl 
or aralkyl, and more particularly are lower alkyl having from 1 to 4 
carbon atoms, or are benzyl, or R.sub.1 and R.sub.2, taken together with 
the quaternary nitrogen atom, are piperidinium or morpholinium; and 
X.sup..crclbar. is a cation, preferably of an inorganic acid, particularly 
chloride, sulfate, or methosulfate. 
Examples of this class of compounds are acryl- and 
methacryl-oxyethyltrimethylammonium chloride and methosulfate, 
benzyldimethylammoniumethylmethacrylate chloride, 
diethylmethylammoniumethyl-acrylate and -methacrylate methosulfate, 
N-trimethylammoniumpropylmethacrylamide chloride, and 
N-trimethylammonium-2,2-dimethylpropyl-1-methacrylate chloride. 
As a rule, these monomers are used in an amount from 5 to 20 percent by 
weight of the copolymer. Adequate diffusion permeability cannot be 
obtained with lower amounts. Higher amounts render the copolymer water 
soluble. The preferred content ranges from 5 to 10 weight percent. The 
amount of these monomers is advantageously kept at such a level that the 
finely divided polymer in pure water will take up from 10 to 100, and 
preferably from 20 to 80, percent by weight of water by swelling. For 
mixing, two copolymers, for example, may be used, one of which takes up 
from 10 to 40 weight percent, and the other from 50 to 80 weight percent, 
of water. 
Suitable nonionic comonomers forming water insoluble homopolymers are 
primarily the alkyl esters of acrylic acid and methacrylic acid, styrene 
and its homologs, vinyl esters, and vinyl chloride. For the purposes of 
this application, nonionic monomers include not only monomers which have 
no ionic groups (such as alkali metal carboxylate or sulfonate or 
tertammonium groups) in the molecule, but also monomers, which are unable 
to form such groups with bases or acids. Alkyl esters of acrylic acid and 
methacrylic acid having from 1 to 8 carbon atoms in the alkyl group are 
preferred. 
The hardness and extensibility of the coating film and the lowest 
temperature at which film formation from the dispersion is possible are 
considerably influenced by this monomer component. Esters of acrylic acid 
will reduce the hardness of the film, increase its elasticity and 
extensibility, and lower the film forming temperature. Since acrylic acid 
esters and the higher alkyl esters of methacrylic acid usually result in 
films that are too soft and sticky when they are used as the sole nonionic 
comonomers, they are preferably used in combination with monomers which 
when used alone form harder homopolymers, for example styrene and the 
lower alkyl esters of methacrylic acid. These esters alone usually result 
in films that are too hard or in a film forming temperature that is too 
high. Higher alkyl groups (having more than 4 carbon atoms), or aryl 
groups, have a hydrophobizing effect and thus reduce the swelling capacity 
and diffusion permeability. Comonomers with such groups therefore should 
be used only when such an effect is intended. 
The advantageous properties of the dispersions in accordance with the 
invention or of the coatings produced therefrom can be brought about with 
the two monomer components described above, that is the quaternary 
ammonium monomers and the nonionic monomers, alone. However, in many cases 
the composition of the copolymer may include other monomers without the 
aims of the invention being jeopardized. However, ionic monomers, as 
defined above, should preferably not be used in an amount greater than 
from 1 to 2 percent by weight of the copolymer. Small amounts of ionic 
monomers, such as acrylic acid or methacrylic acid or the amino monomers 
on which the quaternized monomers are based, occasionally are difficult to 
exclude as impurities of the starting monomers. Water soluble nonionic 
monomers such as acrylamide or methacrylamide, vinylpyrrolidone, or 
hydroxyalkyl esters of acrylic acid or methacrylic acid may appreciably 
influence the swelling and diffusion behavior but will not affect the pH 
independence of that behavior. The amount of such monomers should not be 
greater than 20 percent of the copolymer and is preferably less than 10 
percent or even less than 5 percent. Hydroxyalkyl esters frequently prove 
deleterious and are best avoided altogether. Similarly, ethylenically 
polyunsaturated monomers, which would result in crosslinking, should not 
be used even in minor amounts. 
The production of the copolymer is not part of the invention and may be 
carried out by any desired appropriate method. Bulk polymerization in the 
presence of a free radical-forming initiator dissolved in the monomer 
mixture is simplest. Another method is solution or precipitation 
polymerization in an organic solvent, the polymer formed then being 
isolated from the solvent. What is important in all cases is that the 
copolymer be obtained in the form of a fine powder, which in the case of 
bulk polymerization is accomplished by grinding and in the case of 
solution or precipitation polymerization by spray drying. The powder 
particles should be of a size that will pass through a screen having a 
clear mesh opening of 200 microns. Particle sizes ranging from under 20 to 
50 microns are usable but are not very practical because of their tendency 
to dust. 
As a rule, the mere dispersing of the powdered copolymer in water will not 
result in a stable film forming dispersion. Surprisingly, with prolonged 
stirring at elevated temperature, self-emulsifying particles of a size far 
below that of the powder particles used will form. Their average size 
(weight average) may range from 1 to 50 microns and preferably is between 
10 and 20 microns. To obtain a stable dispersion of the copolymer, it will 
suffice to keep the powder particles suspended by stirring and to prevent 
the formation of a sediment. This can be accomplished by low to moderate 
stirring rates in the usual agitated vessels. Stirring should be continued 
until no sediment forms when the dispersion is allowed to stand. To obtain 
complete emulsification, a stirring time of at least 15 minutes, and 
preferably more than 20 minutes, for examples from 30 to 60 minutes, is 
usually required. There is no need to add emulsifiers. A limit is imposed 
on longer stirring times or higher stirring rates only by gradually 
increasing foaming. 
The formation of the dispersion will be promoted if a plasticizer for the 
copolymer is added at the very beginning. Amounts of plasticizer ranging 
from 10 to 20 percent, based on the weight of the copolymer, will be 
effective during the dispersing process itself and improve the film 
forming capacity in the production of coatings. Nonvolatile additives 
having a molecular weight of generally under 1000 which are compatible 
with the copolymer and are physiologically safe are suitable for use as 
plasticizers. These are predominantly liquid substances or substances 
which solidify amorphously and melt readily, such as polyethylene glycols, 
citrates of lower alcohols, or fatty acid esters of sugar alcohols or 
their ethoxylation products, of which optionally ethoxylated sorbitan 
monooleate is the best known example. 
Dispersions which without the addition of a plasticizer form films only at 
40.degree. C. or 50.degree. C. will give clear and homogeneous coatings 
even from 0.degree. C. to 20.degree. C. when they incorporate a 
plasticizer. 
The temperature required to form the dispersion depends on the hardness of 
the polymer and should be increased with increasing polymer hardness. 
Temperatures ranging from 50.degree. C. to 100.degree. C., and preferably 
from 60.degree. C. to 80.degree. C., will generally be appropriate. The 
ratio between the amount of powder and the amount of aqueous phase should 
be such that a dispersion readily forming a film is obtained. The film 
forming capacity under the conditions of commercial coating methods 
depends on the solids content of the dispersion. When the solids content 
is too low, a uniform film is not obtained or a disproportionately long 
drying time is required. As a rule, good film forming capacity is obtained 
when the copolymer represents from 15 to 40 weight percent and the aqueous 
phase from 85 to 60 weight percent of the dispersion. 
Dispersions with a still higher solids content are difficult to prepare 
because of their increasing viscosity and are difficult to process for the 
same reason. 
While stable dispersions may be produced, stored and marketed in large 
quantities, the processor will find it more advantageous to prepare 
dispersions of the powdered coating composition himself according to his 
short term needs. This makes it possible to use several copolymer powders 
with different swelling capabilities in the required mixing ratio 
depending on the delayed action desired in a given case and, in the same 
operation, to formulate the dispersion with plasticizers and other 
additives as required. 
The application of coatings to pharmaceutical dosage forms by the use of 
the coating dispersions of the invention is conventionally effected by pan 
coating or air suspension methods. Powders or crystals of an active 
material can be granulated conventionally. The preferred use is the 
production of topcoats from 10 to 50 microns thick on pellets or 
granulations, which may be used to fill hard gelatin capsules for example. 
Moreover, the dispersions may be used to manufacture dermal or transdermal 
pharmaceutical dosage forms by embedding active substances in layers of 
film and applying the films to paper sheets or inert plastic foils, or by 
producing unsupported layers of film. 
The dispersions should be processed at temperatures under 80.degree. C. and 
generally not over 60.degree. C. Temperatures under 40.degree. C., for 
example between 20.degree. C. and 30.degree. C. are preferred. During 
manufacture, it should be endeavored to produce coatings or films which do 
not become tacky at temperatures up to 30.degree. C. to 35.degree. C.

A better understanding of the present invention and of its many advantages 
will be had by referring to the following specific examples, given by way 
of illustration. 
EXAMPLE 1 
350 g of water were heated to 65.degree. C. in a flask with stirring and 
150 g of a finely ground bulk polymer comprising 60 parts by weight of 
methyl methacrylate, 30 parts of ethyl acrylate and 10 parts of 
trimethylammoniumethylmethacrylate chloride were introduced into it over a 
period of about 10 minutes. The polymer powder has previously been passed 
through a screen with a clear mesh opening of 0.2 mm. The stirring rate 
was controlled so that the particles were unable to settle on the bottom 
or walls of the flask. The temperature ranged from 65.degree. C. to 
75.degree. C. By the end of 2 hours, a milky, slightly viscous dispersion 
had formed, which was passed through a screen with a clear mesh opening of 
0.1 mm. The oversize was less than 3 g, so that more than 98% of the 
polymer had been dispersed. The solids content of the dispersion was 
30.1%. 
100 g of the dispersion were mixed with 3 g of triethyl citrate as a 
plasticizer. Above a minimum film forming temperature of 17.degree. C., 
clear, readily stripped films formed when the dispersion was brush coated 
onto a PVC plate. 
EXAMPLE 2 
300 g of an aqueous dispersion prepared as described in Example 1 and 
having a solids content of 30% were mixed with 800 g of a pigment 
suspension of 125 g of talc, 55 g of titanium dioxide, 25 g of yellow 
lacquer E 104, 25 g of polyethylene glycol 6000, and 570 g of water and 
were then diluted with a further 500 g of water so that a total solids 
content of 20% was obtained in the lacquer pigment suspension. 10 kg of 
tablets (diameter, 7 mm; height, 3.5 mm; weight, 140 mg each) were 
preheated to about 30.degree. C. in a steel coating cylinder having a 
diameter of 50 cm by blowing in warm air, and a fine jet from an air 
pressure spray gun having a nozzle 1.5 mm in diameter was directed at an 
air pressure of about 1 bar onto the cores rotating in the coating 
cylinder. The spraying rate was held at 25-30 g/minute while drying air of 
a temperature between 40.degree. C. and 60.degree. C. was being 
continuously blown in. Under these operating conditions, the tablet cores 
had a surface temperature of about 25.degree. C. On completion of spray 
coating after 90 minutes, warm air was blown in for another 5 minutes 
while the cylinder was slowly rotated. The coated tablets were then spread 
out on filter paper and allowed to dry further in air overnight. A 
uniformly colored, glossy coating was so obtained. The coated tablets are 
dust-free and easy to swallow. In water, artificial gastric fluid, and 
aqueous buffer solutions, rapid swelling and lifting of the coating film 
occurs within 10 minutes, so that the ingredients of the tablet are 
released quickly. 
EXAMPLE 3 
350 g of water were mixed in a 500 ml round-bottomed flask with 45 g of 
"Tween" (sorbitan monooleate ethoxylate) and heated to 80.degree. C. to 
give a clear solution. Then 50 g of a copolymer comprising 65 parts of 
methyl methacrylate, 30 parts of ethyl acrylate, and 5 parts of 
trimethylammoniumethylmethacrylate chloride, in the form of a coarse 
granulation with a particle size of about 1 to 2 mm, were introduced into 
the solution. The stirring rate was controlled so that no particles were 
able to deposit on the walls. After one hour's stirring, another 50 g of 
the polymer were added, and this addition was repeated after still another 
hour's stirring at 80.degree. C. The mixture was then stirred for another 
5 hours at 80.degree. C. and allowed to cool gradually overnight. The 
milky dispersion was passed through an 0.1 mm screen. The oversize was 
less than 5 g. The solids content of the dispersion was 29%. 
100 g of this dispersion were mixed with 3 g of triethyl citrate and, upon 
drying of a layer formed therefrom, gave a clear but still brittle film. 
When another 3 g of the citrate ester were added, a flexible film was 
obtained, the minimum film forming temperature being 2.degree. C. 
Determination of the particle size distribution by means of an 
ultracentrifuge showed that the average particle size ranged from 150 to 
200 nm. A few particles in the one micron size range were also visible. 
EXAMPLE 4 
350 g of water were heated to 60.degree. C. and 5 g of triethyl citrate was 
dissolved therein with stirring. Then 50 g of a spray dried polymer 
comprising 60 parts by weight of methyl methacrylate, 30 parts of ethyl 
acrylate, and 10 parts of trimethylammoniumethylmethacrylate chloride were 
stirred into the solution. Within 90 minutes a milky dispersion formed and 
was cooled to room temperature with stirring. 
EXAMPLE 5 
400 g of a theophylline powder having a particle size under 0.2 mm, 
together with 160 g of secondary calcium phosphate, were uniformly wetted 
in a kneader with 400 g of a dispersion prepared as described in Example 3 
and then diluted to 15% solids content. This mixture was granulated on a 
granulator having a screen with a clear mesh opening of 1.5 mm. The 
resulting granulation was dried in a hot air oven at 100.degree. C. to a 
residual moisture of less than 2 percent, then again passed through a 1.5 
mm screen, and mixed in a double cone mixer with 6.6 g of talc and 3.6 g 
of magnesium stearate as a lubricant. This granulation was compressed into 
tablets each having a diameter of 12 mm and a total weight of 500 mg, so 
that the content of active ingredient was 400 mg per tablet. In a release 
test run in a paddle apparatus conforming to USP XX (Apparatus No. 2), 
these tablets showed a release of active ingredient delayed for 6 hours. 
EXAMPLE 6 
1.5 kg of microdragees having a particle diameter from 0.5 to 1.2 mm and 
containing 8 percent of chlorophenamine maleate as an active ingredient 
were fluidized in an air suspension apparatus ("Uniglatt", made by Glatt 
of Binzen, West Germany) in a stream of hot air at 50.degree. C. and then 
spray coated over a period of 80 minutes by means of an air pressure spray 
gun having a nozzle diameter of 1 mm at a spraying pressure of 1.8 bar 
with a mixture of 500 g of a dispersion prepared as described in Example 3 
and having a solids content of 30 percent, 30 g of triethyl citrate, 75 g 
of talc, and 700 g of water as a diluent. After 80% of the above 
formulation, which corresponds to a coating which is 8 percent of the 
initial weight of the pellets, had been deposited, samples were taken and 
analyzed in a paddle apparatus conforming to USP XX, Apparatus 2. The same 
was done after the amount of coating was 10 percent of the initial weight 
of the pellets. The test showed a delayed sustained release of the active 
ingredient with the following values: 
______________________________________ 
8% coating deposit 
1 hour.sup. 7.5% pH 1.5 
2 hours 28.5% pH 2.1 
3 hours 55% pH 5.5 
4 hours 73% pH 6.5 
5 hours 84% pH 6.7 
6 hours 92% pH 6.8 
10% coating deposit 
1 hour.sup. 1.5% pH 1.5 
2 hours 8.0% pH 2.1 
3 hours 19.5% pH 5.5 
4 hours 39.5% pH 6.5 
5 hours 59% pH 6.7 
6 hours 71% pH 6.8 
______________________________________ 
Mixtures of artificial gastric fluid and artificial intestinal fluid 
conforming to the British Pharmacopoeia were used as solvents, whereby the 
pH values indicated, which increase from one hour to the next, resulted. 
EXAMPLE 7 
Mixtures of the dispersions prepared as described in Example 1 and 3, each 
having a solids content of 30%, were prepared in the ratios 8:2, 6:4, 5:5, 
4:6, and 2:8. The unmixed dispersions were also analyzed. A sheet of paper 
about 15 microns thick was first wetted with water and excess liquid was 
removed with a rubber roller. Sufficient dispersion was then deposited on 
the paper so pretreated that a film layer 20 microns thick formed. After 
complete drying, the coated paper was inserted in a 12 cm.sup.2 diffusion 
cell of a Sartorius resorption apparatus, model SM 16750, and flushed from 
the coated side with a 36% solution of phenylpropanolamine hydrochloride 
in water and from the other side with an isotonic phosphate buffer 
(according to Hagers Handbuck II, Suppl. Vol. I, p. 125) having a pH of 
6.0. The amount of active substance diffusing through the coating film was 
then monitored spectrophotometrically at 262 nm with respect to time and 
the points of measurement were entered in the diagram of FIG. 1 after 1, 
2, 3 4 and 5 hours as a function of the mixing ratio of the two 
dispersions. It was found that the dispersion prepared as described in 
Example 3 yields films of very low permeability while the films produced 
from the dispersion prepared as described in Example 1 exhibit very high 
permeability. The results obtained with the various mixtures fall between 
these two extremes so that such a diagram can be used to determine the 
optimum mixing ratio for a given active substance in order to match the 
release rate to therapeutic requirements. 
EXAMPLE 8 
10 g of a 10% solution of chlorophenamine maleate in water were mixed with 
100 g of a dispersion prepared as described in Example 3 and having a 27 
percent solids content. 6 g of triethyl citrate were added to the mixture 
as a plasticizer. Sufficient dispersion was then spread coated onto paper, 
as described in Example 7, to form a film about 115 microns thick. This 
film was tested for release of the active substance in a Sartorius 
resorption apparatus as described in Example 7, except that only the film 
side was rinsed with buffer. It was found that there was a delayed release 
of the active ingredient from the film over a period of more than 72 
hours. 
In following Examples 9-16, in each case 350 g of water were warmed to 
60.degree. C. and, in each case, 50 g of finely divided polymer powder 
were added with stirring and further heating. Stirring was continued until 
the formation of a uniform dispersion. The polymer composition (in parts 
by weight) and the conditions of dispersion are given below for each 
example. 
EXAMPLE 9 
The following ground bulk polymer was dispersed over a period of two hours 
at 90.degree. C.: 
60 parts of methyl methacrylate, 
30 parts of ethyl acrylate, and 
8 parts of 2-trimethylammoniumethyl-methacrylate methosulfate. 
EXAMPLE 10 
The following spray dried solution polymer was dispersed over a period of 
two hours at 80.degree. C.: 
60 parts of methyl methacrylate, 
35 parts of ethyl acrylate, and 
5 parts of diethylmethylammonium-ethyl-methacrylate methosulfate. 
EXAMPLE 11 
The following ground bulk polymer was dispersed over a period of three 
hours at 85.degree. C.: 
70 parts of methyl methacrylate, 
20 parts of ethyl acrylate, and 
10 parts of trimethylammoniumethyl-acrylate chloride. 
EXAMPLE 12 
The following ground bulk polymer was dispersed over a period of three 
hours at 85.degree. C.: 
50 parts of methyl methacrylate, 
35 parts of ethyl acrylate, and 
15 parts of trimethylammoniumpropylmethacrylamide chloride. 
EXAMPLE 13 
The following spray dried emulsion polymer was dispersed over a period of 
three hours at 80.degree. C.: 
50 parts of methyl methacrylate, 
38 parts of ethyl acrylate, and 
12 parts of trimethylammonium-2-dimethylpropyl-1-methacrylate chloride. 
EXAMPLE 14 
The following ground bulk polymer was dispersed over a period of three 
hours at 70.degree.-85.degree. C.: 
40 parts of methyl methacrylate, 
40 parts of ethyl acrylate, and 
20 parts of 2-benzyldimethylammoniumethylmethacrylate chloride. 
EXAMPLE 15 
The following spray dried emulsion polymer was dispersed over a period of 
three hours at 85.degree. C.: 
40 parts of methyl methacrylate, 
30 parts of butyl acrylate, 
10 parts of octadecylmethacrylate, and 
20 parts of trimethylammonium-2,2-dimethylpropyl-1-methacrylate chloride. 
EXAMPLE 16 
The following ground bulk polymer was dispersed over a period of two hours 
at 90.degree. C.": 
40 parts of methyl methacrylate, 
40 parts of ethyl acrylate, and 
18 parts of trimethylammoniumcyclohexylmethacrylate chloride.