Note: Descriptions are shown in the official language in which they were submitted.
~ r
J~783
This invcnlion concerns an improved proccss for thc enc~lpsula-
tlon of products by inter~aci~l polymcrization of one or more polymer
formincJ int~ a~es whcrein a stabllizccl disperslon of droplets oE the
substance to b~ encapsulatcd is formed, ancl polymerization (polycon- ;
densation or poly-addition) occurs at the interface`o~ the droplets and
the continuou.s liquid phase in which they are dispersed.
Prior methods of forming droplets of suitable size in int~rfacial
polymerization procedures generally require that a droplet stabilizer
first be dissolved in the continuous phase usually in a separate mixing
l tank employing special agitation equipment. Frequently, the required
stabilizers are such poor emulsifiers tha t the formation of droplets of
suitable size required the use of hlgh shear equipment whlch is expen-
sive, mechanically tr a~ilesome, requires accurate flow-control and li-
mits the rate of production.
The above described prior method of forming dispersed droplets as
the discontinuous phase within a dissimilar continuous liquid phase has
.
been practiced in the past, for example, as disclosed in USP 3, 577, 515.
This patent describes a procedure for encapsulation by in~erfacial con-
densatlon polymerization wherein it is required that a dispersion of one
liquid phase in another be Eormed as an lnitial step, and then in sub~
sequent steps, a polymer walL is farme~ ~ound each drop1et to provide
the desired encapsulated sukstance. It is noted in said patent that,
when the organic phase is the one tobe dispersed, polyvinyl alcohol,
gelatin, and methyl cellulose are effective droplet stabilizers. These
are, by choice, poor emulsifiers that serve only to stabilize the drop-
. :~
: .
~ --2-- !
:
. , . ~ ~
. . ' ' ' ~ . '.
c )
1(?89L'7l~3
lets durincJ polyrneri~ation; an officiell~ emulsifie~r would disperse the
droplets too ~inely.
Likewlse, in 13ritish 1, 371,179, there is described a process for
preparin~7 polyurea capsules by an interfacial p~lymerization technique
5 and, in this process similar stabilizers are employed. Other prior dis-
closures of the preparatisn of encapsulated products by related inter-
facial polymerization techniques include, for example, U. S. Patenl:s
No. 3, 429J 827; 3, 575, 882 and 3, 886, 085; Belgian Patent No.
832, 897; and British Patent No. 1, 416, 294. Such processes have in
common, the dispersion of a substance to be encapsu~ ted as a dis-
continuous phase within a continuous liquid phase. The present inven-
tion will be advantageously employed in any such processes wherein
stabilizers are employed to provide for the formation of droplets of
suitable size in the dispersion.
It is a primary object of this invention toprovidea more efficient
.
method cf prep3ring encapsulat~dsubstances employing an interfacial
polymerlzation procedure wherein the substance to be encapsulated
is more rapidly and easily iormed into dispersed, stabilized droplets
Oe suitable size in a continuous liquid phase.
It is a further object Oe this invention to provide a more ePicient
method of preparing microencapsulated liquids employing an interfacial
polycondensation procedure wherein the formation and size of droplets
o said liquids within a continuous fluid phase is facilitated.
These and other objects are accomplished in accordance with
thls invention which ls a prooess for encapsulatlng products wlthln ~¦
`- "_3_ ~ I
I .
. ~ I .
it4'7~3
a capsulc polymcr wall by an in-L~rfacial p~lymeriz~tion procedur~
wherein a sta~ cd dispersion of droplets of a first liquid to be encap-
sulated is forrrlcd withill a continuous phase of a second liquid, including
the improvement which comprisè.s incorporating a precursor of an emul-
slfying agent for said dlspersion in said first liquid, and then mixlng
said first liquid illtO said second liquid to form said droplets within a
continuous liquid phase, said second liquid having incorporated
therein a component reactive with sàid precursor for forming said emul-
sifying agent whereby said emulsifying agent is Eorrned in situ, said
precursor and component reactive therewith being incorporated in said
first and second liquids in amounts sufficient to provide an amount o
emulsifying agent sufficient to improve the stability o sald dispersion.
The emulsifier which is formed in situ, as disclosed herein, may
be anionic, cationic or non-ionic depending on the liquid system em-
:
: 15 ployed inthe lnterEacial polymerization technique.
In a preferred embodiment of this invention, the liquid of the dis-
persed droplet phase is an organic liquid, more preferably, an organic
liquid whlch is to be encapsulated by interfacial polycondensation
:~ while the continuous phase or second liquid is an aqueous medium more
preferably containing at least one ingredlent that will ultimately react
to become part of the capsule wall.
In the practice of the preerred form o this invé~fnion, a controlbd
amount of one reactive component of an anionic emulsifier is dissolved
ln one of the liquid phases, and the remaining reactive component or
compon~ts dissolvedin the other liquid phase. When the phases are
~ ~ . , .
~ ~4~
; 4~83
are brought together w~th only mild a~itation, sufficiently stabill~ed
droplets are rapLdly produced. For example, in the preparation of
encapsulated products wherein the contlnuous phase is aqueous, a fatty acid
is dissolved in the organlc phase and a base is diqsolved in the aqueous phase.
Preferably, the base is dissolved in the aqueous phase before the addition of
the organic phase thereto, although the base may be added to the aqueous
phase simultaneously with the organic phase. On conventional reactor mixing,
stabilized droplets are efficiently formed because the stabilizer is produced
where it is needed, i.e., at the interface.
The amount of emulsifier to be formed varies with the system and the
particle size desired, but for systems employing aqueous media as the
continuous phase, it is typically in the range of 0.05~ based on the weight
of the dispersed phase. Thus, sufficient amounts of each of the emulsifier
precursors are employed to provide the desired amount of in situ ~ormed
emulsifying agent.
This new process eliminates the need for special mixing equipment and
lengthy mixing times for preparing stabilizer solutions, and also eliminates
the need to employ high shear mixing devices for dispersing the droplets. In
actual practice several hours can be saved per batch of encapsulated material,
the process control requirements are greatly simplified, and frequently,
much higher-solids dispersions can be prepared. The eEEicient technique of
this invention lends itself especially well to continous production.
In the preferred practice of this invention any oE a wide variety of
surfactants or emulsifiers can be formed at thè phase interface, for example,
carboxylates, sulfonates, sulfates, and phosphates in which the cation is
either a metal or an amine. Obviously, the choice will depend on the
particular overall system and will be made so as not to adversely interfere
with the capsule-wall forming reaction. Most commonly, the cation precursor
component for the emulslfier will be a metal. Particularly useful are the
- 5 - ;
'
~0~ 83
alkali metals including Na ~3, K ~and Li , wlth Na6~being especially
preferred.
A wlde variety of anions are applicable and are well kno~l to those
famillar with dispers:Lon technology.
The choice of anion or catlon or mixtures thereof, will depend on the
particular system oE interest. C16-C18 aliphatic fatty acids, for example,
oleic, stearic and palmitic acids, have been found to be generally useful as
the anionic precusors component for the emulsifier, and oleic acid is
.
preferred for the preferred embodiment.
A good review of anionic, cationic and non-ionic surfactants is -~
presented in the Kirk-Othmer "Encyclopedia of Chemical Technology", 2nd Ed.,
Vol. 19, pp. 512-566. `
As more specific preferred examples of polymerization reactions to
which the present encapsulation process is applicable, the following may be
mentioned: Diamines or polyamines in the aqueous phase and diacid or polyacid
chlorides in the organic phase are reacted to yield capsule walls consisting
oE p~y rides. Di~mLnes or polya-ine~ in
'.
~; ~ ''; ~ . "
'~ ' ' ~;'''
- 6 -
-, f~
783
the aqucous liquid and l~lsc~lloroforlrlatos or polychloroEormates in the
organlc liquid afford a polyuretll~ne capsule skin. Agaln, diamines
or polyamines in l:he aqlleous medium antl disulfonyl or polysulfonyl
chlorides in the ~rganic solv~nt pr~uce a pc>lysulfonamide skin. Like-
wise, with diamines or polyamines in the aqueous phase, a polyurea
capsule wall is obtainable when the organic phase contains phosgene
(chloroformyl chloride) which, for convenience oE classification herein,
may be considered to have the properties of a difunctional acid chloride,
i. e., in some correspondence with diacid chlorides such as sebacoyl
chloride. Also, diamines or polyamine s in the aqueous media and
diisocyanates or polyisocyanates in the organic solvents produce a
polyurea sl~in.
With diols or polyols in the aqueous liquid, various other con-
densate resins are achieved. Thus with diacid or polyacid chlorides
in the organic phase, polyesters are produced to constitute the capsule
wall. When bischloroformatesJ polychloroformates or phosgene are
used in the organic liquid the capsule skins are polycarbonates. Not
only are there other complementary intermediates which react to orm
polycondensates in a direct manner useful in the interfacial poly-
condensation proaess~ enaapsul~tlon, but various mixtures of inter-
mediates may be employed in either or both liquid phases. For oxampl0,
mixtures of diols and diamines in the aqueous liquid and also or alter-
natively, mixtures oE acid chlorides and chloroformates in the organic
solvent are useful to achieve corresponding condensation copolymers.
A primary example of a condensation copolymer is one formed with a
. , "
7l~3
difunctional acid chlorlde, e. g. sebacoyl dichloride; a multifunctional amine,
e.g. ethylene diamine/diethylene triamine mixture; and a polyeunctional
isocyanate, e.g. polymethylene polyphenyllsocyanate. This copolymer has been
referred to as a crosslinked polyamide-polyurea (amide-urea copolymer). Also,
diols or polyols in the aqueous liquid and diisocyanates or polyisocyanates in
the organic liquid produce a polyurethane skin. ;?
In the system for interfacial polymerization wherein a stabilized ;~
dispersion of droplets of a first liquic1 to be encapsulated is ~ormed within a
continuous phase of a second liquid, the two liquids should be immiscible, at
least one of them being an organic liquid, and the other preferably an aqueous
medium. A wide variety of organic solvents may be employed, e.g., as will be
recognized to be appropriate for the selected intermediate or intermediates.
Some examples, are mineral oil, xylene, benzene, carbon disulfide, carbon
tetrachloride, pentane, and the like, as well as liquids which may not only
serve the function of a solvent for the polymer-forming reactant but may also
have a reactant function to be availed of after formation of the capsules.
Instances of such reactant liquids which in the encapsulation steps of the
invention serve simply the function of an organic solvent are styrene and
di-t-butyl peroxide.
,~.
Examples of difunctional acid-derived compounds are sebacoyl
chloride, ethylene bischloroformate, phosgene, terephthaloyl chloride,
adipoyl chloride, azelaoyl chloride (azelaic acid chloride)S dodecanedioic
acld chloride, dimer acid chloride, and l,3-benzenesulfonyl dichloride.
. . .
; ' ' ' ' ' '
....
, .
~'~
- 8 - i;
,
. '; '.
'' ' ' ' '~
.... .. , , . . ,. . . , . , .: . . . .
Polyf~lnctlonal compl~unds o~ tllis type are exempllfied by trlmcsoyl
chloricle; 1, 2, ~, 5 benzene tcl:raacid chloride; l, 3, 5-~_nzene l:risulfonyl
chlc>ride; trlmer acid chloride; citrlc acid chloride; and l, 3, 5-benæene
trischloroformate. Intermediates similarly useful in the organic phase
also include diisocyanates and polyisocyanates,for example,toluene
diisocyanate, hexamethylene diisocyanaie and polymethylene
polyphenylisocyanate, e. ~., P~lPI~The Upj ohn Co. ) .
As examples of suitable diols for use as intermediates in an
aqueous phase, there may be named bisphenol A[2, 2bis (p, p'dihydrox~
diphenyl) propane], hydroquinone, resorcinol, catechol, and various
glycols such as ethylene glycol, pentanediol, hexanediol, dodecanediol
:
and the like. Polyfunctional alcohols e. g. triols, are exernplified by
pyrogallol (l, 2, 3-benzenetriol) phloroglucinol dihydrate, pentaerythritol,
trimethylolpropane, 1, 4, 9,10-tetrahydroxyanthracene, 3, 4-dihydroxyan-
thranol, diresorcinol, tetrahydroxyquinone and antralin.
Suitable diami.as and polyamlnes, usually selected as water
soluble per se or in water soluble salt form, where such reactant is to
be included in an a~ueous phase, are: substances eEfective as difunc-
tional reactants (contributing no significant cross~linking effect of
themselves~, namely ethylene diamine, phenylene dlamine, toluene
diamine, hexamethylene diamine, cliçthYlere triiamine. pipera~in~^ an~J
substances effecti~e as polyfunctional reactants (contributing cross-
linking effect, and usèful alone or at least in combination with another
amine of at least dif~ctional character), namelyl, 3, 5-benzene triamine
trihydrochloride, 2, 4, 6-triamino toluene trihydrochloride, tetraethylene
': `
? ~ &~ 9
. .
, . ' ,,,,'.
4t~83
pentamine, pentaethylene hexamine, polyethylene-imine, 1,3,6-triaminonaph-
thalene, 3S4,5-triamino-1,2,4-trla~ole, melamine, and 1,4,5,8-tetraminosnthra-
quinone. To t~e extent that the reactant to be used in the aqueous phase may
be insoluble or have limited solubil~ty in water per se, it may be used in a
form or with appropriate cooperating substances to render it, in effect,
soluble. Thus, certain amines may be used in hydrochloride or other salt
form, while a compound of little or no water solubility (by itself), such as
bisphenol A, may be used in a composition appropriately ad~usted as with
alkali, to afford such solubility.
Interfacial polycondensation to form the capsule wall as shown in
British Patent No. 1,371~179 provides a reac~ant amine by the hydrolysis of
an isocyanate which reactant amine in turn reacts with a free isocyanate to
form the polyurea enclosure (capsule wall). After the dispersion establishing
droplets of the organic phase within a continuous liquid phase has been
accompllshed, and preferably with moderate agitation of the dispersion~ the
formation of the polyurea capsule wall around the dispersed droplets i9
brought about by heating thecontinuous liquid phase or by introducing a
catalytic amount of a basic amine or other agent capable of increasing the
rate of isocyanate hydrolysis, and optionally in addition, ad~usting the pH
of the dispersion, thereby effecting the desired condensation reaction at ~:
the interface between the droplets and the continous phase.
~ The organic polyisocyanates contemplated in the above described
process are those members of the aromatic polyisocyanate class which
~'~ '','
-- 10 --
,
, ................................. . . . . . .
7~
includes the aron~atic diisocyanates, the aliphatic diisocyanate class, high
moiecular weigllt linear aliphatic diisocyanates and the isocyanate prepolymers.
Representative of the aromatic diisocyanates and other polyisocyanates are the
following:
l-Chloro - 2,4 - phenylene diisocyanate
m-Phenylene diisocyanate
p-Phenylene diisocyanate
4,4'-Methylene bis (phenyl isocyanate)
2,4 - Tolylene diisocyanate
2,6-Tolylene diisocyanate
60% 2,4 Tolylene diisocyanate and 40% 2,6 isomer of Tolylene diisocyanate
80% 2,4 Tolylene diisocyanate and 20% 2,6 isomer of Tolylene diisocyanate
3,3' - Dimethyl - 4,4'-biphenylene diisocyanate
4,4' - Methylene bis (2-methylphenyl isocyanate)
3,3' - Dimethoxy - 4,4' - biphenylene diisocyanate
2,2', 5,5' - Tetramethyl - 4,4' biphenylene diisocyanate
Polymethylene polyphenylisocyanate (PAPI)
By forming a stabilizing agent in situ at the interface of the
discontinuous and continuous phases, the production of encapsulated
products by the interfacial polymerization process, as exemplified by USP's
3,429,827, 3,575,882, 3,577,515 and British 1,371,179, is greatly simplified.
Surprisingly, the addition of the same amount of the preEormed stabllizer
to either phase gives totally unsatisfactory results, usually
- 11 -
. .' , , , ' , ',,
re~Ult~ J lna co~r5c slurry of capc;ule wall polymer.
.~ 1
The capsulcs formed using the techniqucs of th~ invcntion have
the same utility as those produced by thc prior art methods.
The following examples serve to Illustrate the method of this
invention.
EXAMPLE I
To a 250 mL Erlenmeyer flask equipped with a magnetic stirrer is
charged 90 g. deionized wa~er, 0. 95 g. sodium carbonate, 0. 93 g,
ethylene diamine, and 1. 07 g. diethylene triamine. Then, with rapid,
agitation, a premixed blend of 10 g. xylene, 1. 5 g, sebacoyl chloride,
0. 5 g. polymethylene polyphenylisocyanate, and 0.1 g. oleic acid
is added. Capsule formation ls observed almost immediately; however,
stirring to complete polymerization, is continued for two hours. Micro-
.
scopic examination of the resultant slurry shows xylene-containing
.
, capsules having an average diameter of ca, 25 microns.
EXAMPLE II
Using the procedure of Example I, the iolloY~ing reaction is per-
formed. ~ mix oi:
90 g. delonized water
1. Sg. sodium hydroxide (50% aqueous)
0. 93g. ethylene diamine, and
1. 0 7g . diethylene triamine
is prepared and to it the follo~ng pre-mix i9 added with agitation:
~: . ' .
~ 10 g. xylene
:
~ 1. 5g, sebacoyl chloride
. ~ , ' .
12
-- o
~OB4783
O. 5~. pol~7methylone polyphenol isbcyanate, and
0.1 g. palmitic acid,
~fter stirring for two hours~ the run is shut down and the product
is examined. Complete encapsulation is observed microscopically;
S spheroids of (a, 50-microns average size are found. No xylene sepa-
ration is evident. The slurry contains ca. 9. 5% encapsulated xylene
by weight.
EXAMPLES III - XVIII
To a one liter resin flask iitted with stainless steel baffles and
an agitator,is charged the ingredients of Part A. Then, with fairly
i
vigorous agitation, a pre-mix of the ingredients oE Part B is added to
form a dispersion. A pre-mix of the ingredients o~ Part C is added,
and the reactor c~ntents are stirred for two hours to aomplete the poly-
merization. Finally, Part D is added for post-stabilization and pH
adjustment.
The individual recipes are given in Table I, and results and
comments are presented in Table II
....
.
' .,
. ' , ' .
I3
: ~ : :
. ~ ~, .
.~ . , .
:' . ' , ' . :'
'7~3
.
~,
_ _ _
o~a p ~ o IJ- ~ ~D I O ~ , o (D ~ ~ O a~ o P
~ ~ ~ It ~ rr ~ O ~ ~ ~Pl ~ ~ O ~
P' ~ ~ p J P ~ P ~ p~~ rt 3 ~ ~ .Q I' P.
î~ o (D p ~D ~D ~ O O , ID p ~
~_ ~ ~ ~Po g ~ ~ ~ 'C C UC~ ~E; ~ `;
P ~ p t~ ~ ~ h g ~ O- P ~ p o~
fD P o p~ o 1'- 1~ (D ~ ~ O ~I) O~
O 1- n n P~ p ~ ~ ~ ~ - ~ O ~D ~ o~o ~ ~1 It
~ ~ p~ D o ~ P rt ~ (D Y îT~ ~ ~ ~
O~ P~ ~D 1~ ~ ,u.
~_ I W IDO rh ~ ::~ O 1~ 0~ D P O
o ~ ~ E. ~ ,, tD ~:: P ~, ~q
_ P~O n O ID ~ n C ~ ~n
~ ~ r~ ~ Ep~ 'q p p ph ~
~ I_ o P~ /D p~ ~ i,
. '~ ~* ~ 0~ - '~.', ;'~,
. \ ~ . ~":
. ,'" '
.'
_ . 1_ _ _ ~3
I I ~ I O I I I I I I I ~ I O I I I I I ~ H ~;
1~ o o~ ~o o a~ O . ~ ~ H 1
~_. __ _____. H Pl
1--~ ~11 q~ ~9 $ a~ o o $ ~1~ g C H
. ~_~ ~i- ' ' ~ ~ `
n I~n I III III~n~Ig IIIII~IO C . ' '~.
~ ~ ~Jl I H CO ~n I I O I C
. _ ~ . .
: ~ . I 1~ ~n l l OI I I I ~ I O . ~ C :
~ ~ Ul ~/1 0~ Jl O ~Jl O H
,~___ .. Ul _ ~ IJ . ~ ' C .~ ,
00 Ul l.n I I I I I I i`~ . . O~ ~Jl O H
_ _ ~Vl IJ7, __ . _ H
I ....... t- l I I 'I I I ' I I Ul ~ I I I I I I ~ ~ t~! E
u~ oo ~ 11 . i~ ~11 0 W ~
~C~ . . ___ 11~_ ~ w ~
.----~i;F I I I ~ li --I H
, C~CJ~ ~O C O ~ W ~
I 1_ l l 1 I I I I I . I O I I I I I 1, ~. H
Ul ~ n C O ~J~ ~JI 0 ~n O H
. . l O IJI ~11 1- W
It!~ _. _, C0 ~n ~ C O H
O1--I ~n`~JI g I I I I 1~ ~0 1 O O H
__y_Co -~- ~F _.~- ' ~ ~ C
~ I .; O I I I I 1. 1 1 1 ~n I I I ~ ~ I I I I ~ ~
I I ~ o cr~ ~o o . I ~ c
_I . . C I I I ~ .n I C I ~ I I I l l Ci~ H
_
. I I O I . C I I I I H I I I ~n I ¦ . ~. C I
* ~ ~ ._ __
~. ~ . ._ ~ . ' ' I_ . `. C ~.~
I V, Vl I I II I I I I Vl V~ O I )-- I I I I O H ~ .
: . H
. . _ _
.~ . .
4r~3
X 5~ iC C ~ E! ~
. ~
~ v O ~ ~ m
c~. O O ~ P ~~ ~
, ~ ,.
. ' . ~ .
: I ,L o~ O ~
i~
. . .
~3
. ~i ,.
' ~i .
~ : ~ ~
:: in~' . ~
~w
1 ~
''' 1 .
~'` 1 ` ~ .
~: 1:
.
. .
. ~ 15
: :
,
o
7~33
D ~
~a
.
. 3 . ~ '
o
,H- . t
~i
1 ~ o
~ ~' ~ . ~i, '.
' ~. trJ
. ~L N t
~' . ' ~. ~
q 8
~ h ~ ¦
.
~: ~ ~:
' ~: : ~ ~
~ ~ 1~
