Characterisation of the interactive properties of microcrystalline cellulose–carboxymethyl cellulose hydrogels
Graphical abstract
The process of the hydrogel broken down under the shear.
Introduction
Microcrystalline cellulose (MCC) is used in the pharmaceutical industries because of its interactive behaviour nature and its biodegradability. Its crystalline nature and its involvements in hydrogen bonding processes make significant contributions to the physical properties and to the chemical properties of compositions, in a variety of environments (Kennedy, 1995). In its chemistry, cellulose can be viewed as behaving as an acid (when in the presence of a base), as a base (when in the presence of an acid) and as an ampholytic species, under appropriate circumstances. The appropriate chemical reactivity then follows. Physically, cellulose swells considerably in a number of fluid systems but does not dissolve in these (Hebeish and Guthrie, 1981). Exceptions are claimed to be the cellulose-NMMO system and solutions of cellulose in ionic liquids (Manning, 1985, Zhu et al., 2006).
Microcrystalline cellulose is a product of the wet granulation of cellulose that has been partially de-polymerised via hydrolysis in hydrochloric acid. The process helps to remove the disordered regions of the cellulose, only the highly ordered regions remaining (Biopolymer, 2008). The general compatibility of MCC changes during the granulation process. The reasons for such changes are not fully understood (Suzuki et al., 2001, Badawy et al., 2006). However, it is clear that microcrystalline cellulose has significantly different physical properties relative to those of the parent cellulose system. The mechanical disintegration of microcrystalline cellulose (MCC) in an aqueous dispersion, whereby at least 1% of the dispersed cellulose is broken down to sub-micron cellulose crystallites, gives thixotropic gels (Barrista, 1961). Drying these gels at elevated temperatures, at atmospheric pressure, gives a hornifiedproduct in which the gel-forming, sub-micron crystallites are hydrogen-bonded together and can no longer be liberated on subsequent redispersion in water, without the substantial input of energy. Such gels are also sensitive to flocculation by the addition of an electrolyte (Durand, 1970).
The addition of sodium carboxymethylcellulose (Na-CMC) during the mechanical disintegration of MCC reduces hornification. Hence, the pharmacopoeial description of the co-processed product concerns a “co-attrited, colloid-forming mixture” (USP-NF, 2008a). The co-processed product is also known as Dispersible Cellulose (BP) and Cellulose Gum (European Pharmacopoeia, 2008b), in addition to the National Formulary titles of microcrystalline cellulose and sodium carboxymethylcellulose (USP-NF, 2008a). Pharmacopoeial grades of MCC/Na-CMC are marketed by FMC BioPolymer under the trade names Avicel® RC and Avicel® CL. The primary pharmaceutical application of MCC/Na-CMC is to provide structured media for the suspension of active pharmaceutical ingredients. The stabilising system is a mixture containing 8–13% of Na-CMC within the commercial Avicel RC 591 (1995).
Hydrogels formed from MCC/Na-CMC are commonly used in formulations of orally taken products and nasally dosed products (Sharpe et al., 2003, Zietsman et al., 2007). This type of hydrogel gives the required rheological characteristics because it forms a thixotropic system at a low loading, in aqueous media. The yield stress of the gel is relatively high, providing good stability with respect to maintaining the suspension of suspended particles. For applications such as in intranasal spray delivery, the viscosity needs to be low at high shear rates due to the requirements of the spraying action. The rheological properties of compositions that contain hydrogels of MCC and Na-CMC have been studied (Walkling and Shangraw, 1968, Rowe and Sadeghnejad, 1987). However, characterisation studies have not been extensive because of limitations in the sensitivity of the available instrumentation. Recently, the rheological properties of the hydrogels have been evaluated using controlled stress rheometry (Rudraraju and Wyandt, 2005a, Rudraraju and Wyandt, 2005b, Mihranyan et al., 2007). However, interpretation of the data relating to the microstructure of hydrogels, with respect to the influence of intermolecular forces, has not been undertaken to any great extent.
Section snippets
Materials
The microcrystalline cellulose (MCC), sodium carboxylmethyl cellulose (Na-CMC), and Avicel RC 591 were supplied by FMC Biopolymer, Cork, Ireland. MCC and Na-CMC are the components of commercial Avicel RC 591. Deionised water was used to make up the appropriate solutions and dispersions.
Sample preparation
Following a detailed study, Rudraraju concluded the optimal gel formation loading for Avicel RC 591 to be around 1.5% (Rudraraju and Wyandt, 2005a). Thus, for the current work, three appropriate loadings of
Molecular mass determination
The weight average molar mass and the polydispersity of Na-CMC used in the experiments were 4.5 × 105 g/mol and 3.55, respectively. The relatively high weight average molecular mass provides the Na-CMC with the physical properties that are needed to ensure structure in the aqueous fluids that contain the Na-CMC. This structure provides a basis for the controlled flow behaviour that is so important to the delivery of the fluid in a specific application: that of dispensation onto nasal cavities, the
Conclusions
MCC is widely used in pharmaceutical formulations as a suspending agent. The physical interactions that occurred during hydrogel formation, breakup, and recovery have been studied rheologically. Intermolecular interactions, including hydrogen bonding and ionic interactions play an important role in these processes. Dispersing Avicel RC 591, a commercial mixture of MCC and Na-CMC in water gives rise to hydrogels, having a 3D network structure. The network structure has been visualised by SEM and
Acknowledgment
The authors acknowledge the valued contributions made by the EPSRC (Dorothy Hodgkin award for G.H.Z).
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