Chapter 5
Plasticized Cellulose Acetate Latex as a Coating for Controlled Release Thermal and Mechanical Properties
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V. L. King and T. A. Wheatley Pharmaceutical and Bioscience Division, F M C Corporation, Princeton, N J 08543
Plasticizers were studied to examine their effects on the thermal and mechanical properties of films cast from a new CA latex. The latex was an aqueous dispersion of cellulose acetate (CA398-10) with a solids content of 29% and mean particle diameter of 310 nm. Plasticized films were studied by thermal mechanical analysis (TMA) and tensile testing. Plasticizers selected included glyceryl diacetate (GDA), glyceryl triacetate (GTA), triethyl citrate (TEC), acetyltriethyl citrate (ATEC), and dibutyl sebacate (DBS). They were studied at use levels of 0-160%. GDA, GTA and TEC were clearly the most effective in altering the glass transition temperature (Tg) and elastic modulus of the latex films.
Over the past decade, aqueous coatings have aroused interest in the pharmaceutical industry largely because of the need to avoid problems associated with organic solutions such as air pollution and solvent toxicity. As a result of this interest, latexes of two cellulosic derivatives (ethylcellulose and cellulose acetate phthalate) have been introduced to the market. Previously, these materials were formulated only as organic solvent-based systems. Cellulose acetate (CA) has been used for many years in the development of osmotically controlled drug delivery systems. Typically the CA is in the form of a membrane made by dissolving the CA and plasticizer in a non-aqueous solvent system, followed by deposition onto a solid substrate, i.e., tablet, employing typical film coating techniques. The use of a CA latex dispersion eliminates the need for solvents in the formulation and manufacture of these coated systems. There is now available a cellulose acetate latex (CA398-10) dispersion produced from direct emulsification of the polymer, a tecrmique taught by Vanderhoff et al. and Bindschaedler. Bindschaedler et al. have investigated the mechanical properties of films produced from cellulose acetate latexes containing various plasticizers. They concluded that "Provided that a suitable choice is made of plasticizers and filmforming conditions, cellulose acetate latexes yield strong membranes". The objective of this study was to investigate the mechanical and thermal properties of CA latex films containing other plasticizers that are widely used and accepted in the pharmaceutical industry. 1,2
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0097-6156/93/0520-0080$06.00/0 © 1993 American Chemical Society
In Polymeric Delivery Systems; El-Nokaly, M., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1993.
5. KING AND WHEATLEY
Plasticized Cellulose Acetate Latex as Coating
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Experimental Methods The cellulose acetate ( C A ) aqueous dispersion was manufactured at the F M C Coatings Plant, Newark, Delaware, U $ A . The latex has a solids content of 29 wt% and a median particle diameter of 310 nm as determined by centrifugal sedimentation analysis. Samples of plasticized latex films (0.50-0./0 mm thick) were studied by thermal mechanical analysis ( T M A ) utilizing a Perkin-Elmer T M A - 7 instrument. Probe penetration into the sample was measured at 5°C/min heating with an applied force of 1 m N . The films were prepared by adding the C A latex to a dispersion of plasticizer in water, and mixing for J 0 minutes to yield a final total solids content of 2 0 % . Films were cast onto an aluminum substrate and dried for 18 hours at 60°C. Theplasticizers studied were glyceryl diacetate ( G D A ) , C P . H a l l C o . ; triethyl citrate (TEC) and acetyltriethyl citrate ( A T E C ) , Morflex; glyceryl triacetate ( G T A ) , Eastman; and dibutyl sebacate (DBS), U n i o n Camp. Thin films (80-100 μπι thick) for tensile testing were prepared in a similar manner, but were cast onto a glass substrate, dried at 60°C for 18 hours and stored for 5 days in dessicators prior to testing. A n Instron model 1011 instrument was used for the stress/strain measurements, and was equipped with a 5-kg load transducer and adjusted to test the films at 1.0 mm/min strain rate with a 50-mm gauge length. The tested films were of rectangular shape (80 χ 19.3 mm) and were cut precisely to size using a fresh razor blade and steel template. Thicknesses were measured as an average of ten micrometer measurements across the gauge length of each film. Results a n d Discussion The effectiveness of the five plasticizers for C A latex have been established under the conditions of this study. These plasticizers have G R A S status or at least some degree of approval for use in foods or food packaging as defined i n their specific Title 21 C F R listings. Their chemical structures and physical properties, such as bp > 250°C, qualify them as suitable candidates as plasticizers for cellulose esters, particularly the cellulose acetate (CA398-10) used in the latex. Thermal mechanical analysis ( T M A ) was used to investigate the effectiveness of the plasticizers in lowering the glass transition temperature (Tg) of C A latex films. W i t h T M A the glass transition is often associated with the first mechanically detected softening point of a polymer. For this study the plasticizer content was varied from 0-loO% of the latex solids. Plasticization plays an important role i n the application of pharmaceutical latex coating formulations and is usually critical for the formation of good polymer films. Plasticizers, i n general, w i l l greatly reduce the critical film forming temperature of a polymer. They soften ana swell latex spheres, which aids the particles in overcoming their resistance to deformation and facilitates film coalescence. This is best achieved by adjusting the glass transition toward reasonable coating processing temperatures. A properly plasticized f i l m , once formed and dried, w i l l also exhibit the desired physical strength and flexibility for its application as well as the desired permeability. T M A data shows the effects of the fiveplasticizers on the onset glass transition temperature of C A latex and is presented in Table I and Figure 1. W i t h respect to lowering the glass transition or softening temperature of the latex it is readily apparent that the rank order ofplasticizer effectiveness, from best to worst is: G D A > T E C > G T A > A T E C > D B S . Glyceryl diacetate and triethyl citrate are the most similar in terms of polarity and general chemical structure to C A 3 9 8 - 1 0 , the polymer in C A latex. Both of these plasticizers have a hydroxyl group present along with ester functional groups. The cellulose acetate polymer has a degree of substitution of approximately 2.6 for acetate groups and Ô.4 for hydroxyl groups. It is, therefore, reasonable and consistent for G D A and T E C to be the best plasticizers of the group studied in terms of lowering the glass transition temperature. Both of these plasticizers are able to lower the T g of the latex films below room temperature as indicated by T M A . A clearly poor plasticizer is D B S , which is capable o f depressing the T g only a few degrees across the 0-160% range of plasticizer levels studied. The three best plasticizers, which were capable of forming very good free films, were also examined for their effect on the mechanical properties of latex
In Polymeric Delivery Systems; El-Nokaly, M., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1993.
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POLYMERIC DELIVERY SYSTEMS
Table I.
T h e r m a l M e c h a n i c a l Analysis of C A Latex F i l m s Plasticizer E f f e c t on Onset of Glass T r a n s i t i o n , T g
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Plasticizer Level (% of Solids)
GDA Tg ( ° C )
TEC Tg ( ° C )
GTA Tg C C )
ATEC Tg C O
0%
164
164
164
164
20%
114
40%
99
107
109
131
60%
65
80%
31
62
86
109
120%
26
37
79
103
160%
