Interactions of gelatin—acacia microcapsules with surfactants

%llotds und Surfaces, 4 (1982) 163-1'71 Blscviet Scientific Pubtishing Company, Amsterdam -Printed

INTERAtX’IONS SURFACI’ANTS SHIRO SUZUKI

OF GELATIN-ACACIA

and TAMOTSU

163 in The Netherlands

MICROCAPSULES

WITH

KONDO

PerriP Women’s College, Naka-ku. Yokohama 231 .zad Faeufly o/Pharmaceutical SGettces. ScCence Uni&wrsilyo.CTokyo. Shinjrrku-ku, Tokyo (JaPanl (Received January 27,1981;

162

accepted in final form November 26, 1981)

ABSTRACT Gelatin--acacia mkcocapsuks containing water were prepared from those containing olive oil by extracting the oii with acetone and replacing the sotvent by ethanol and then by water. Their interactIons with ~taolcyeQyleneglycaI-l*d~~ecyl ether (ODE), sodium L-dodecyt suffate (SDS). and l-dodecylpyridinium chloride (DPyCl) were studied at different pH and tank strengths of themedium. The nunionlc surFactant was found to cause disintegration ot Ihecap&s at very high concentrations if pH was low, irrespective of the ionic strength of the medium. On the other hand, ODE did not break down the capsules at high pH. In media of low pH, the cape&s were disrntegrated by 9DS at relativety law concentrations white the solubWzed potymers were precipitated by high concenkatkns of the anlontc aurfactant. The degree of disintegratkn decre,lsed as pH of the medium rw_ An increase in the tank strength of the medium brought about an increase in the amount of the precSpiCatedpolymers at high surfactant concentrattons. I’ery tow cancentratfons of DPyCl produced agcegation of the capsules at all pH values studled. As theaurfactant concentration increased, the capsules underwent diainCegration and then the sotubilized potymers were salted out with Further fncreae of the autfactant concentration. Adsorption erperhnenk Indicatedthat the ohserv+d disintegration phenomenon of the capsuks b due to monolayer and/or bilayer aurfackmt adsorption on the constituent potymecs,

INTRODUCTION

The procedure of preparation of gelatin--acacia microcapsules is now well established [I-41. Coacervate drops formed in the geIatinacacia system under strictly controlled conditions are used to coat the core material, either solid or liquid, dispersed as fine particles in the sol&on. MicrocapsuIes are obtained by cooling the solution down to room temperature or below and treating the gelatineacacia wall on the core material with giutaraldehyde or formaldehyde. Recent papers [S,6] have dealt with disintegration of uncrosslinked, negatively charged polyamide microcapsuIes by high concentrations of cationic surfactants. This phenomenon was interpreted as showing that the negatively charged polyamide molecules con&ituting the microcapsules are sotubilized

164 by surfactant cations to disperse into the soIution .as positively charged polyions. As gelatin is well known to form precipitation complexes with opposi+ ly charged surfactants, which can he completely resotubilized by excess surfactant [?-101 f it will be interesting to see what will h:\ppen if geIatinucacia microcapsules interact with surfactants. The understanding of this sort of interaction is also important for evaruating the stabiSity of microcapsules. This paper describes the interaction of gelatin--acacia microcapsules with nonionic, anionic, and cationic surfactants at different pH and ionic strengths of the medium, EXFERRUENTAL Swfudants The surfac~=~ts used were octaoxyethyleneglycol f-dodccyt ether (GDE], sodium ldodecyl sulfate (SDS), and I-dadecylpyridinium cbloridc [DFyCI). Their purities were claimed to be 99.9,99.0, and 98.5%, respectively.

Gelatinqcacia micracapsutes were prepared by a method quite sirnib to that used by Luzzi and Gerraughty C3]. Seventy ml of olive oil was dispersed into 50 ml of 10% aqueous gelatin (pH 6.0) solution at 4WC. To this O/W emulsion was added 50 ml of 10% aqueous acacia solution at 40”C, followed by addition to the mixture ot 230 ml of &&Ned water pr&ous~y kept at 40°C, When the pH of the mixture was adjusted to 4.0 with cc&c acid* coacervation was brought about, the coacervates gathered around the oil drops and enclosed them. The system was cooled down to 5OC to cause gefation of the coacervats protein. One ml OPformaIin (35%) was then added, and, while stirring, sodium hydiulxide was ad&d to the system to raise the pH to 9.0. After stirring had continued for 30 min, the temper&we was elevated at a rate of l°Clmin. When the temperature reached SO%, curing of coacerrates was compteted and microcapsule walls were formed. The microcapsules thus obtained were separated by centrifugation and washed several times with warm distilled water. The washed microcapsules were treated successively with acetone, ethanol, and distilled water. This way, olive oil ~&asextracted and eventually replaced by water, and water-baded geIatin-acac ia microcapsules dispersed in water were obtained [ll]. Their diameters ranged from 60 to 200 cun with a mean value of about iaopm. 06serwtion

of

the state of microcapsules

The state of gefatinqcacia microcapsules in the presence of surfactant was observed as follows, To the suspension of geIatinacacia microcapsules in test

tubes was added an equal volume of a series of various concentrations of aqueous surfactant solution. The pH and ionic strength of the medium were adjusted by the addition of HCl or NaOH and NaCI, respectively, The mixtures were ailowed to stand for 1 h with occasional shaking in a thermostatted bath at 3OOC. At the end of this period, a smalt portion of each of the mixtures was withdrawn by a capillary tube and placed on a slide glass to observe the state of gelatin-cacia microcapsules under an optical microscope. In addition, the sedimented state of the microcapsules in test tubes was observed visually after the capsules settled in the tube bottom to see the effect of surfactant concentration on the degree of capsule disintegration in terms of sedimentation voIume.

Measurement of stirfuctuntadsorption Surfactunt adsorption onto gelatin--acacia microcapsuQs was measured by an equilibrium dialysis technique in the same manner as that empbyed before [S,61. The amount of adsorption was calcuIated from the difference between the surfactant concentrations before and after adsorption. A madtiication of the Grcff-Setzkorn-Leslie method was adopted to determine the concentration of ODE [12]. The concentrations of SDS and DPyCl were determined by the Weatherburn method [!31 and the FewOttewill rrkethod (141, respectively. These methods gave an accuracy within 6% in the adsorption mcasurcment,

AWcroetectrop)roresis Microelcctrophoresis of gelatin--acacia microcapsules was carried out at using a microelectraphoresis apparatus (Rank Brothers Co., Ltd., England) in the absence and presence of surfactant.

3WC

RESULTS

AND

DISCUSSION

Qc&uuxyethyteneglycol-r-dodecyl ether ODE caused partial disintegration of gelatin--acacia microcapsules at high concentrations (lo-’ M or above) at low pH while the cnpsures were not broken down by the nonionic surfactant at high pH. There wss no appreciable effect’ of ionic strength. Capsule disintegration seems to result from sofubilization of the formalin-treated gelatin molecules. The microcapsules treated with higher concentrations of formalin for a longer time than those described in the Experimental Section never underwent disintegration however high the concentration of ODE, SDS, or DPyCl was. This suggests that gehtin-acacia microcapsules highly crosslinked with formalin are hardly soh~bilized by surfadaM just as ;‘n the ease of poly (Na, NE-L-.lysinediylterephthaIoyl micro-

166 capsules sufficiently crossIinked with glutaraldehyde (51. As soIubilization should be preceded by surfactant adsorption, it is important to get information about the adsorption of the nonionic surfactant onto geratinacacia microcapsules. The adsorption of ODE molecules onto gelatin-acacia microcapsules was larger at low pH than at high pH. Adsorption isotherms at 30°C of ODE on gelatin-cacia microcapsules at different pH are shown in Pig. 1, where the number of ODE ntolecuIes adsorbed on a capsule is plotted against the initial concentration of the surfactant to make it easy to compare the data on adsorption with those on disintegration. .

Pig. 1 Adsorp6ion iso the(30-C)*

of OEM3an gdatin~cada

micracapsules at different pH

The shape of the adsorption isotherm and the chemical structure of ODE strongly suggest that molecules of the nonionic surfactant adsorb on gelatinacacia microcapsules to form a monomolecular tayer with their long alkyd chain anchoring on the hydrophobic moieties of the capsules and oxyethylene chains directed towards the aqueous phase. Comparison of the adsorption data with the disintegration data seems to indicate that the number of adsorbed ODE molecubs should exceed a certain value (ca, 2 X 10IS molecules per capsule) to give rise to soIubiIization of capsules. It has been reported that when complexes are formed between nonionic surfactants and polymeric acids, hydrogen bonding of oxygen atoms of polyoxyethylene chains of the former with carboxyl groups of the latter plays an important role and the number of hydrogen bonds formed increases with decreasing ionization 02 the carboxyl groups or pH of the medium [15]. In view of this, the effect of pH on the adsorption of ODE on gdatin~cacia microcapsules could be explained in terms of the number of protonated carboxyl groups on the gelatin and acacia molecules constituting the capsuks,

pH 7.0 Pfg- 2, State of gefatin~cacia SDS at different pH.

mIcrocapsules

in the presevxe of variaus concentrations

of

168

Sodium ldodecyl sulfate gave rise to disintegration of gelatin-cacia and caused preciflitation microcapsules at low concentrations (10 ‘s-lOaAf) of solubilized gelatin molecules at high concentrations (lO%f and above). The degree of disintegration increased as pH of the medium decreased. ionic streng.?hhad practically no effect on the disintegration phenomenon whik

precipitation of the soIubilized polymers was enhanced by increased ionic &err&h to give large sedimentation volumes. This is shown in Fig. 2,

The adsorption of SDS on gehtinacacia microcapsules was considerably affected by pH of the medium whereas it remained unchanged in a range of ionic strength O.Ol--O.L within experimental error at a constant pH. In Fig. 3 adsorption isotherms at 30°C of the allionic surfacratit on the microcapsuIes in the media of different pH are iltustmtcd.

Pig. 3. Adsorption

(30°C).

isothermsof SDS an gehtin-acacia mkrucapsufes

at

differeat PEC

It is quite IikeIy that, at low pH, most of the amino soups which have not reacted with formalin and other basic groups of the gelatin molecules constituting the microcapsules are protonated to produce cationic sites for DS ion adsorption. Hence, DS ions will adsorb not onty on the cationic sites forming ionic bonds but ako on the lyophilic moieties through hydrophobic interaction. This will make DS ion adsorption larger at low pH than at high pH where the number of protonated basic groups of gelatin is smaller than that at iow pEf. Moreover, the increased number of dissociated carboxyl groups on the polymers of the microcapsules at high pH reduces DS ion adsorption due to strong electrostatic repulsion between the anionIc sites and the anions.

169

PH

pH

5.0

7.0

Fig. 4. Statu of gelatin-acacia DPyCl at diffeerent pH,

micracapsules in the presence of various concentrations of

270

At high concentrations of SI1S, a second layer &sorption of IX ions begins

to form onto the catknic sites a&e&y occupied by aS ionk of the

micra-

capsules through hydrophobic bonding, with their ionic h&adsdirected outwards. This type of DS ion auction con~butcs algo to so~ubj~~at~o~ of the gelatin molecules of the micracapsules. The second kzyerackoxption was verified by microelectrophoresis of the n&cmcapsuIesat law pH. Thus, thcr capWes migrated to the anode in an e&&tic field if SDS was present in an amount large enough to cause disintegration while they were positlvety charged in the absence of the su~fac~nt- Ifoweuer, the second fayer adsorption of SDS has no direct relation to its CMC since the capsuks are disintegrated by the enionic surfactant of 110% at an ionic strerrgthof 0.01, which is far betow the CMC. These adsorption data correspond well to the findings on the d~int~t~on phe~~me~o~* increase in ionic strength promotes the s&&g out of the ~o~ubil~z~ and dispersed potymers of the rn~c~o~psu~~-

I-Dod~cylpyridiniu’um chluride

*

I

10-J

10-J

IO“ DIJ&I

-.

IO-

llr

mol &a-’

Pig. 5. Adsorption &otherrtts of IWyCl OILgelatin--peacla m&rocapautes at different pEf (3cPC).

171

M), disintegratbn of the micracapsules and sotubilization of the polymers of the capsufes at moderately high concentrations (UP'-UP2 M), and ptecipitation of the solubilized polymers at high concentrations (LO’* M and above),

irrespectiveof pH of the medium, though the DPyCl concentration range in which each of these phenomena took place shifted upwards gradually with increasing pH (see Fig. 4). Adsorption of DPy ions onto geratinacacia microcapsules exhibited a

feature quite different from that of the ODE or SDS adsorption. The number of DPy ions adsorbed was highest at pH 7.0 and lowest at pH 2.0. Adsorption isotherms at 30°C are given in Fig. 5 at different pH of the medium. As the sites of adsorption of DPy ions are evidently negatively charged

carboxyl groups of gelatin and acacia motecuIes, it is natural to expect that DPy ion adsorption increases with increasing pH since the degree of dissociation of the carboxyl group becomes higher a~ pH rises, thus yielding a larger

number of adsorption sites for DPy ions at higher pEI_ When all adsorption sites are occupied by DPy ions, thus completing a singfe Iayer adsorpt.ion, DPy ions begin adsorbing through hydrophobic interaction on the long alkyl chains of adsorbed DPy ions to form a second layer of the surfactant cation on the polymers constituting the microcapsules, thereby promoting disintegration of the capsutes and solubilization of the polymers. Microelectrophoresis of the capsules in the presence of 1W3M DPyCL is evidence of the daubto layer adsorption of the catiouic surfactzmt. This adsorption behavior of DPy ions is in parallel with their disintegrating action on the microcapsules, REFERENCES 1 B.K. Green and L. Schteiker, U.S. Pat, 2,800,458 (1957). 2 B.K. Green and L. Schleihxr, U.S. Pat. 2,730,466 (2956). 3 LA. Luzzi and R.J. Qerraughty, x Pharm. Sci., ti3(1964) 429. 4 LA. Luzzi and R.J. Cferraught,‘, J. Pfwm. SC&, ~56(19671634. 5 S, Suzuki, T. Nakamura, hf. Arakawa and T. Kando, J. Cultaid Interfuce Sci, 71U9793

141.

6 S. S~tuki, T. Nakainuraand T. Kondo, f?ul#.Chem. Sot. Jpn.. 52(1979)3176. 7 P.W. Putnam and H. Neuraach,J. Am. Chem. SOC.. 66(1944)692.

8 F.W. Putnam and H+ Newath, J. Am. Chem. Sue., 66( 1944)lWZ 9 E.D.GoddardandB.A.Pethtca,J, Chem.Soc..(1951)2659. LO F.Karush andM.Sanenherg.J. Am. Chem.Suc.. 71(1949)1369. 11 1.Jakeniak and T. Kondo, J. Pharm. ScL. 70 (1981) 456 12 A. Nozawa, T. Ohmurr and T. Sekine, Anutyst. 101(1976)643. 13 A.S.lUeatherbum,J.Am. Oil Chem_Soc..28(1951)233. 14 A.V.Fewand R.H.Ottewili,J. CalIbid Sci, 11(1956)34. 16 S. SaitoandT.Tdniguchi,J. Col?o