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..

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The byproduct was separated from the product-solution by vacuum filtration. The filtrate was concentrated, and the product was precipitated out by adding it to five times excess of diethyl ether. The product was separated by vacuum filtration to separate the ether soluble impurities from the product. The product so formed was purified by recrystallizing it from its solution in dichloromethane. The final purified product was dried under vacuum.

Figure 2
IR spectral analysis was performed to ascertain the completion of the reaction. The IR spectrum of the product was compared with those of pure PEG and pure polyacrylic acid (i.e., acrylic acid polymerized without PEG). The vital peaks present in the IR spectrum of PEG were at 3463 cm–1 because of the –OH stretch, 2917 cm–1 for the alkyl–CH stretch, and 1099.3 cm–1 for the ether (–C–O–C–) group. The main peaks in the IR spectrum of plain polyacrylic acid are: –OH stretch at 3386.5 cm–1 , –CH stretch at 2926.8 cm–1 , and –C=O stretch at 1720.6 cm–1 . Whereas in the spectrum of the synthesized-PEGDA (see Figure 2), no peak was observed in the range of 3200–3600 cm–1 (i.e., peak because –OH stretch was absent). These interpretations showed that all the –OH groups of PEG have reacted with the –COOH group of acrylic acid. A shift in peak because of the –C=O stretch was observed, from 1720.6 cm–1 in acrylic acid to 1761.6 cm–1 in the case of the product. The peak at 1761.6 cm–1 is because of the carbonyl stretch in the case of the esters. This shift further confirmed the synthesis of PEGDA. Another characteristic peak because of ester linkage, (i.e., a distinct and sharp peak because of the C(=O)–O– group) also was seen at 1199.3 cm–1 in the spectrum of PEGDA.

Synthesis of hydrogels. Because there are two reactive terminal hydroxyl groups in PEG, these macromers (PEGDA) contain two acrylate groups per molecule. Upon free-radical polymerization, these macromers form a cross-linked three-dimensional gel.

The hydrogels were prepared by the copolymerization of acrylic acid monomers, and the synthesized PEGDA by radiation-induced polymerization. Initially, a heat-initiation technique was adopted for preparing the hydrogels, which was faster compared with the radiation-induced polymerization technique. Because the heating process could not be controlled, preparation of the hydrogels could not be reproduced. For further studies, therefore, the hydrogels were prepared only by radiation polymerization.

Again, both bulk- and solution-polymerization methods were tried for synthesizing the hydrogels. The solution polymerization in aqueous medium was comparatively faster than bulk polymerization. The polymerization of the acrylates was determined by the time presence of –H and –OH radicals in the H2O molecules in the dispersed phase. This condition may be attributed to the release of –H and –OH free radicals from the water molecules, which helps in the initiation and propagation of polymerization. The PEG molecules further are capped with hydrophobic polymerizable units, thereby forming micelle-like structures in water. The effective concentration of the double bonds within the micelles increases, thereby increasing the rate of the propagation reaction in free-radical polymerization. The radical-termination reactions are diffusion-controlled and are retarded with the increase in viscosity of the medium, which restricts the segmental motion of the involved polymer radical. An increase in the propagation rate and a decrease in the termination rate results in a high polymerization rate and rapid gelation (29).


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