Biomacromolecules 2001, 2, 886-893
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Rheological Evaluation of the Interactions between Cationic Celluloses and Carbopol 974P in Water Rosalı´a Rodrı´guez, Carmen Alvarez-Lorenzo, and Angel Concheiro* Departamento de Farmacia y Tecnologı´a Farmace´ utica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15706 Santiago de Compostela, Spain Received March 6, 2001; Revised Manuscript Received April 25, 2001
This paper reports on the influence of the structural properties of two cationic hydroxyethylcelluloses, polyquaternium-4 (PQ-4; 1.13-1.27% N) and polyquaternium-10 (PQ-10; 1.88-1.95% N), on the rheological behavior of their dispersions and of the dispersions of their blends with Carbopol 974P (60.9% COOH) in water. Dynamic shear oscillation measurements showed that the rheological behavior of 1 and 2%(w/w) cellulose polymers was mainly viscous. Flow curves of PQ-10 dispersions presented a higher consistency and pseudoplasticity than PQ-4 dispersions, in which the thixotropy was higher. Structural features, such as type and distribution of substituents and molecular weight, explain why they behave different. The presence of 0.00125-0.02% Carbopol in diluted cationic cellulose (0.01-0.08%) dispersions produced an important decrease in viscosity, due to a strong associative process via an electrostatic interaction phenomenon. Similar results were obtained when sodium acetate was added instead of Carbopol. In contrast, in the concentrated range (1% cellulose polymer), the viscous (G′′) and especially the elastic (G′) moduli of the dispersions increased monotonically with Carbopol concentration (0.010-0.125%) and became physical gels, except in the proximity of the neutralization of the ammonium groups (0.07% Carbopol for PQ-4, and 0.1% Carbopol for PQ-10) in which G′′ and G′ decreased. The concentrated dispersions showed pH-sensitivity when the Carbopol added was around or above the neutralization point. In dispersions with this composition, consistency increased dramatically when pH changed from 4.5 to 7.4. This property can open a wide range of applications, especially in the pharmaceutical field to prepare gelling in situ systems. 1. Introduction Cationic polysaccharides (i.e., cationic celluloses, cationic guar, amino-modified starches, chitosan, and chitosan derivatives) are large-scale commercial products that have many useful characteristics such as hydrophilicity, biodegradability, and antibacterial properties. This group of polymers, just like anionic and nonionic polysaccharides, can interact effectively with water, causing the medium to thicken. After drying, they can easily form biodegradable films and membranes with good mechanical properties. These features make them very interesting substitutes for synthetic polymers.1 In addition, owing to their amino/ammonium groups, cationic polysaccharides can adsorb contaminating metals2 or bentonites3 from aqueous streams, and show a natural attraction for some components of the skin and the hair (sustantivity).4 This attraction increases the time that the dispersions remain on a biological substrate, and if a drug were incorporated, the absorption process would be more efficient. This makes them particularly useful as bases for cosmetic preparations or topical drug delivery systems.4 The ability of cationic celluloses to thicken is usually not as greater than that of other cellulosic polymers but can be enhanced extraordinarily by the presence of oppositely charged surfactants.5-7 The changes in viscosity and the * Corresponding author. Telephone: 34-981-594627. Fax: 34-981547148. E-mail:
[email protected].
formation of aggregates or polyelectrolyte complexes have been attributed either to electrostatic interactions between the charged groups, or to hydrophobic interactions of the nonpolar tail of the surfactant and the backbone and alkyl substituents of polysaccharides, or both.7,8 However, surfactants may also have undesirable physiological effects on the components of human skin.9 In consequence, the development of stable surfactant-free pharmaceutical formulations with appropriate thickening and suspending properties is being studied.10,11 Recently, polyelectrolyte complexes of chitosan with anionic polymers such as dextran sulfate,12 polygalaturonic acid,13 or poly(acrylic acid)14 have been characterized. These hydrogels exhibit pH responsiveness, which is especially important for developing “rheologically smart” fluids or carriers for the release of pharmacologically active compounds.15,16 In the 60s, Michaels et al.17 reported the formation, properties, and applications of polyelectrolyte complexes. The formation of polyelectrolyte complexes is governed by the characteristics of the individual components (e.g., properties and position of ionic sites, charge density, rigidity of macromolecular chains) and the chemical environment (e.g., solvent, ionic strength, pH, and temperature).18,19 Usually, the formation of the complex is possible in a narrow pH range, especially when weak polyelectrolytes are used, and in a way similar to the cooperative binding process of biomacromolecules. The process does not occur with low
10.1021/bm010049c CCC: $20.00 © 2001 American Chemical Society Published on Web 06/09/2001
Rheological Evaluation of Interactions
Figure 1. Schematic molecular structures of polyquaternium-4 (PQ-4) and polyquaternium-10 (PQ-10).
molecular weight substances. This suggests that the cause of exchange reactions between oppositely charged polymers is the cooperative interaction of sufficiently long sequences of functional groups attached to a chain. The initial contact between two complementary macromolecules takes place accidentally at some point along the polymer chains. Further interaction proceeds between ionic groups adjacent to the recently formed links, since these groups are sufficiently close to each other. As a result of such a process, a zipped or double-stranded structure is formed. Polyelectrolyte complexes have a huge potential for many practical applications, such as thickener additives, to form membranes with selective retention ability or as a model to study complex living systems in which biomacromolecules are ionically associated.18,19 The aim of this study was to characterize two cationic celluloses, polyquaternium-4 and polyquaternium-10 (Figure 1) (a backbone of anhydroglucose units with pendant aminoalkyl groups), and compare their rheological behavior in order to evaluate the influence of the structural properties on their interaction in aqueous solution with an oppositely charged polymer, Carbopol 974P. The influence of temperature and pH in the biological range was also considered with the aim of preparing in situ gelling pharmaceutical systems, i.e., liquid systems with rheological properties that are sensitive to the physicochemical conditions of the application area. The information obtained could provide a deeper insight into the potential of cationic celluloses for biomedical applications, given their reduced acute and chronic toxicity.20 2. Materials and Methods 2.1. Materials. The materials used were as follows: Polyquaternium-4 (PQ-4) (Celquat H-100, FGS 1014, National Starch and Chemical Ltd., UK); polyquaternium-10 (PQ-10) (Celquat SC-230M, batch GFS 1139, National Starch and Chemical Ltd.); Carbopol 974P (60.91% carboxylic content, batch AB17796, BFGoodrich Europe);
Biomacromolecules, Vol. 2, No. 3, 2001 887
purified water by reverse osmosis (MilliQ, Millipore Spain) with resistivity
