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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As the prepared hydrogels were washed and dried before characterization, the type of polymerization technique used (bulk or solution polymerization) imparted no significant change in the physical properties of the hydrogels. The faster technique (the solution-polymerization method) was continued for further preparation of the hydrogels.


Figure 3
Radical polymerization was accomplished by exposing the polymerizing mixture (i.e., the aqueous solution containing the monomer and cross-linker) to UV radiation (365 nm) using a photochemical reactor (Jain Scientific Glasswares, Ambala, India) for 36 h. Completion of polymerization was evident from the change in the physical state of the reaction mixture. The reaction mixture initially was in the form of a liquid, which gradually thickened as the polymerization took place. A flexible solid mass was formed upon the completion of polymerization. In this way, the hydrogels were prepared using PEGDA of various molecular weights and in different weight ratios. PEGDA, being a bifunctional agent, can serve as a cross-linker in the present copolymerization reaction (see Figure 3).


Figure 4
As the molecular weight of the cross-linker is increased, the molar percentage will decrease for the same weight percentage. With the increase in the molecular weight of PEGDA, therefore, the cross-link density would decrease. This change follows the prediction made by the chemical representation of the copolymeric PEG-acrylate hydrogels containing PEGDA of different molecular weights (see Figure 4). It is assumed that for the same molar ratio of PEGDA, the size of the pores might increase with the increase in molecular weight.

Purification and drying of hydrogels . The polymerization was done until a solid mass was formed that may contain some unreacted monomers, either entrapped in the matrix or adsorbed on the surface. Purification of the hydrogels that were formed was essential before their further use. The purification was carried out by soaking the prepared hydrogels in a hydroalcoholic mixture for 24 h. The acrylate monomers, being soluble in water, came out in the aqueous system used for washing. The washing medium was tested intermittently for the presence of any extractive by spectral analysis by scanning in the UV range against a suitable blank. Completion of purification was confirmed by the absence of any absorbance in this range.

Swollen hydrogels have lower mechanical strength and further provide surface for microbial growth. The purified hydrogels were dried to help in their further handling and storage. Drying was performed under hot-air stream flowing over the hydrogel surface using a hot-air sterilizer oven for 2 h at 60 C, followed by 2 h of drying in a vacuum oven at 45 C. The two steps for drying were followed because fast drying in a vacuum oven can create a dried, glassy shell around the hydrogel's surface, which can considerably slow down the drying process. Air-drying, therefore, is done because it can uniformly remove the moisture without creating a dried, glassy shell around the hydrogel's surface. A major portion (approximately 70–80%) of the moisture can be removed by air-drying. After this initial drying, the residual moisture (i.e., the remaining 20–30%) can be removed effectively with a vacuum oven (30).


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