Modification and Characterization of Gellan Gum

The authors modified gellan gum using microwave technology and showed it can be used as an excipient in tablet formulations.
Jul 02, 2009
Volume 33, Issue 7

Carbohydrate polymers have been widely used in the formulations of pharmaceutical solid dosage forms becasuse of their biodegradability and lack of oral toxicity. Gellan gum (commercially available as Gelrite or Kelcogel) is a gel-forming polysaccharide produced by the microbe Sphingomonas elodea (formerly Pseudomonas elodea) and approved for food use by the US Food and Drug Administration in 1992 (1, 2). The gellan polymer consists of monosaccharide α-L-rhamnose, β-D-glucuronic acid, and β-D-glucose in a molar ratio of 1:1:2 linked to form a linear primary structure (3).

The native polymer is a high acyl gellan containing O-5-acetyl and O-2-glyceryl groups on the (1-3)-linked glucose residue. When exposed to alkali at high temperatures, both acyl groups are hydrolyzed, and the deacylated form of low acyl gellan is obtained. Low acyl gellan dissolves in water at temperatures >90 °C. The low acyl solution forms gels in the presence of cations when cooled to gelling temperature (4). High acyl gellan solutions gel at much higher temperatures than do low acyl gellan solutions. High acyl gellan gels are very weak because the bulky acetyl and glyceryl groups prevent close association between gellan polymer chains in a double-helix formation and hinder compact packing of the cross-linked double helix. Aqueous solutions of gellan gum form gels on warming to body temperature and in the presence of cations (5). The mechanism of gelation involves the formation of double helical junction zones followed by aggregation of the double helical segments to form a three-dimensional network by complexation with cations and hydrogen bonding with water (6–8).

Gellan gum has been widely accepted for various pharmaceutical applications, although it has not been explored as a disintegrant in a tablet formulation. Gellan gels have been studied for application in ophthalmic drug delivery (9–11), oral sustained delivery (12, 13), beads (14), sustained delivery beads (15), controlled-release hydrogel with scleroglucan (16), and floating in situ gelling (17).

Since the implementation of polymeric materials in the field of pharmaceutical technology, numerous attempts have been undertaken to modify their physical and chemical properties and apply them in drug formulations. These approaches include cross-link polymers through covalent bonds using chemical and physical means. Formaldehyde, gluteraldehyde, and epichlorohydrin are among the most commonly used chemical means of cross-linking. Ultraviolet (18, 19) and gamma radiations (20) and temperature variations represent physical methods of cross-linking. Modifying temperature is one of the most favorable approaches because it avoids both the application of harsh chemical materials suitable for large-scale production and does not require a diversity of equipment and methods in the application (21).

Microwave technology is a growing interest in the pharmaceutical industry. Various applications include drying pharmaceutical excipients (22), granules (23-26), film coats (27), sterilization of ampules (28), and formulation of controlled-release beads (29).

Microwaves consist of thermal and nonthermal components. Microwave is a high-frequency radiation (300 MHz to 30 GHz) that possesses both electrical and magnetic properties. Transmitting microwave radiation results in the vibration of molecules by induced or permanent dipoles, thereby rapidly creating heat within the molecule. The intensity of vibration is a function of the quantity of microwave energy absorbed by the molecule. This value depends on the size, shape, and polarizability of the molecule as well as the extent of intermolecular bonding. Practically, the amount of energy absorbed by a molecule, P, is defined as:

in which f is the frequency of microwave, E is the electric field, E 0 is the dielectric constant of free space, Er is the dielectric constant of molecule, and tanδ is the loss tangent. The dielectric constant of a molecule is related to the polarizability of its constituent material, and the loss tangent is regarded as a measure of molecular interaction. Polar materials with a high level of molecular interaction are expected to absorb more energy, giving rise to a more intense molecular vibration and heat. The state of molecular interaction of an object may change its physicochemical properties over time (30, 31). Microwave heating offers rapid heat transfer, high speed, energy penetration, selective energy absorption, and instantaneous electronic control. It also requires compact equipment, fewer British thermal units (BTUs) and is environmentally clean.

Cross-linking natural macromolecules with microwave energy might solve toxicity problems resulting from remaining traces of chemical cross-linking agents and in vivo biodegradation products of chemically cross-linked macromolecules. This approach may help identify new uses for an existing excipient, which is relatively inexpensive and simpler than developing a new excipient.

The authors modified gellan gum by microwave technology and compared its various physicochemical properties with those of pure gellan gum. Confirmation of physical modification was carried out with differential scanning calorimetry (DSC) and X-ray diffractomy. Chemical changes in the modified material were analyzed with Fourier transfer infrared (FT-IR) spectroscopy. Optimization of the amount of distilled water and time of exposure in microwave was carried out using a 32 full-factorial design. Tablets of lactose and dibasic calcium phosphate that also contained modified gellan gum were prepared, and the effect on tablet disintegration time, hardness, and friability were measured.