Abstract

DEVELOPMENT AND IN-VITRO EVALUATION OF HYDROGEL POLYSACCHARIDE BEAD CONTAINING ATENOLOL FOR CONTROLLED DELIVERY

Umesh Kumar Chaurasiya*, Ishak Khan and Vijay Nigam

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Abstract

Atenolol, a β-blocker, is prescribed widely in diverse cardiovascular diseases, eg, hypertension, angina pectoris, arrhythmias, and myocardial infarction. The drug is also frequently indicated in the prophylactic treatment of migraine. Atenolol is a polar cardioselective β-blocker, widely used alone or in combination with other drugs for treatment of various cardiovascular conditions. It is slightly soluble in water with reported half-life of 6-7 hours. It is considered a drug with low jejunal permeability and a low extent of absorption, therefore it has an oral bioavailability of about 46-62%. Administration of conventional tablets of atenolol has been reported to exhibit fluctuations in the plasma drug levels, resulting either in manifestation of side effects or reduction in drug concentration at the receptor site. Accordingly, studies have been reported on regulation of drug release by formulating its diverse CR systems such as hydrophilic matrices,9 osmotic pumps, and transdermal drug delivery systems. In the recent times, polysaccharide based bead for controlled delivery are gaining importance in the design of oral controlled drug delivery systems. Carrageenan has been used increasingly in pharmaceutical formulation studies, for example, microcapsules for sustained delivery, crosslinked spheres for controlled release. Carrageenans are naturally occurring high molecular weight polysaccharides extracted from red seaweed. They are made up of alternating copolymers of 1,3- linked ß-d-galactose and 1,4-linked 3,6-anhydro-α-dgalactose. Carrageenan forms a gel with potassium ions, but also shows gelation under saltfree conditions. However, gels prepared in the presence of metallic ions were substantially stronger than those obtained under salt-free conditions. The gelling and melting temperatures of kapp-carrageenan are dependent almost solely on the concentration of potassium ions. When a polyelectrolyte (like carrageenan) is combined with a uni/multivalent ion of the opposite charge, it may form a physical hydrogel known as an „ionotropic‟ hydrogel. Ionotropic hydrogel, which may degrade and eventually disintegrate and dissolve, are held together by molecular entanglements, and/or secondary forces including ionic, H-bonding or hydrophobic forces. All of these interactions are reversible, and can be disrupted by changes in physical conditions such as ionic strength, pH, temperature, application of stress, or addition of specific solutes that compete with the polymeric ligand for the affinity site on the protein. From these characteristics, kappa-carrageenan is used as an entrapment matrix for drug and enzymes as well as for pharmaceuticals and food adjuvants. In the past, conventional crosslinked potassium- kappa-carrageenan beads have been investigated for the development of a multiple unit drug delivery system. The purpose of this study was to prepare and evaluate the carrageenan gel beads as a new controlled drug release system for atenolol. Another purpose is to investigate the conditions in which the polymer bead is formed, and hence the dependence of the drug release on bead formation.

Keywords: Controlled, hydrogel, polysaccharide, crosslinking, microspheres.