Copolymerized PEGlyated Acrylate Hydrogels for Delivery of Dicolofenac Sodium - Pharmaceutical Technology

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Copolymerized PEGlyated Acrylate Hydrogels for Delivery of Dicolofenac Sodium
Hydrogels are biocompatible drug delivery systems by which the physical properties can be controlled by the cross-linking density. Hydrogels were prepared by copolymerization of acrylic acid monomers in the presence of poly(ethylene glycol)(PEG) to form polyethylene diacrylate (PEDGA). Various molecular weights of PEGs were used for the synthesis of PEGDA to study the effect of molecular weight of PEG on the properties of hydrogels. These hydrogels were further characterized for free water, swelling..

Pharmaceutical Technology

All of the properties of the hydrogels, including hydration capacity, diffusion, and drug release, can be correlated to the porosity of the polymer matrix. Porosity of the hydrogels also can be determined by the diffusion studies (24). The diffusion study of the drug from drug-loaded hydrogels and their simple aqueous solutions was carried out using dialysis tubes of pore size 2.4 nm (Himedia, Mumbai, India), and the diffusion coefficients were calculated. The relation between these two diffusion coefficients can be expressed in terms of the Mackie & Meares' equation:

in which d and d o are the diffusion coefficients of the drug from the hydrogel and aqueous solution, respectively, and ε is the porosity of the hydrogel.

Results and discussion

Acrylate hydrogels are generally prepared using N,N'-methylene-bisacrylamide (BIS) as a cross-linker, and N,N,N',N'-tetramethylene-diamine (TEMED)/ 2, 2-azo-bis-isobutyronitrile (AIBN), and ammonium peroxydisulfate as initiators (25). These reagents may be toxic for living cells (26, 27). In addition, they may lead to the formation of brittle structures if used in high concentrations.

Copolymerization can be used to produce hydrogels of desired mechanical properties (8). In the present work, copolymerization of acrylic acid was carried out in the presence of PEGDA to avoid the chances of toxicity and to prepare hydrogels with good mechanical properties. Being a PEG derivative, PEGDA is biocompatible and nontoxic (28). PEGDA is a bifunctional polymer and as such also can act as a cross-linker. PEGDA mainly functions as a cross-linker using comparatively lesser amounts of PEGDA (1%) (20–22). But in this experiment, it was used as a template for polymerization when the polymerization of acrylic acid monomers was carried out in the presence of PEGDA. Hydrogels of PEGDA also were reported, but those are mainly PEG hydrogels. In the present study, only two acrylate groups were there for each PEG molecule, and the aim was to prepare PEG-acrylic acid copolymer-based hydrogels. Such copolymers can improve the physicochemical properties of polymers comprised of only acrylic acid. In the present study, monomeric acrylic acids were polymerized on the terminals of PEG-acrylates using 25–75% PEGDA as the template for acrylic acid copolymerization. This process then modifies some physical properties of only polyacrylic acid hydrogels. PEGDA of various molecular weights were used in different concentrations to study the effect of concentration and molecular weight on the properties of the hydrogels that were formed.

Figure 1
Synthesis of PEG-diacrylates. The cross-linker, PEGDA, was synthesized in the laboratory by the esterification reaction between PEG and acrylic acid monomer in dichloromethane. The esterification reaction is catalyzed by the addition of dicyclohexyl carbodiimide in the reaction mixture. The schematic representation of this reaction is shown in Figure 1.

Because bifunctional PEGs were used, the reaction could take place at both the ends. Stoichiometrically, all of the other reactants were used in amounts twice as much as the amount of PEG used in the reaction. Addition of some excess of reactants, however, always is preferred in reactions involving macromolecules such as PEG to overcome the steric hindrance provided by their bulky structures. Acrylic acid monomer, therefore, was used in a five times molar excess quantity as compared with the stoichiometrically calculated value. The esterification reaction took place in the reaction mixture of PEG and dichloromethane in dicyclohexyl carbodiimide in 5 min after the addition of acrylic acid. The precipitate of dicyclohexyl urea started appearing, and stirring was continued for 4 h to complete the reaction. An ice-cold temperature was maintained to precipitate out dicyclohexyl urea, completely.


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