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

Table I: Composition of different hydrogel formulations used in the present study.
Synthesis of polyethylene glycol diacrylate. PEGDA was prepared by using an esterification reaction, involving acrylic acid and PEG of various molecular weights (see Table I). Weighed amounts of PEG were dissolved in dichloromethane and mixed with a twice-molar solution of dicyclohexyl carbodiimide in dichloromethane. Acrylic acid then was added (in five times molar excess) into this solution with stirring. The stirring was continued for 2 h at room temperature followed by 2 h of stirring on an ice bath. The precipitate of dicyclohexyl urea byproduct was filtered out by vacuum filtration, and the volume of the filtrate was reduced using a rotary vacuum evaporator (Superfit, Mumbai, India). The product (PEGDA) was then precipitated by adding this concentrated filtrate to an excess of diethyl ether with continuous stirring. Vacuum filtration again was performed to separate the precipitated product from the solvent. PEGDA then was purified by dissolving in dichloromethane and reprecipitating with diethyl ether. Finally, the purified product was dried under vacuum in a vacuum oven (Jyoti Scientific, Gwalior, India) and then stored in a vacuum desiccator until use. PEGs of various molecular weights were used for the preparation of the copolymers.

IR spectroscopy was performed to confirm the formation of an ester linkage between PEG and acrylic acid. The IR spectra of the reactants (acrylic acid and PEG) and the product (PEGDA) were compared for any change in vital peaks. The samples were compressed with potassium bromide in the form of pellets and analyzed using a Fourier transform IR spectrophotometer (PE 1600, Perkin Elmer, Waltham, MA).

Preparation of hydrogels. Polymerization of an acrylic acid monomer was carried out in the presence of PEGDA by radiation polymerization using a photochemical reactor. Solution polymerization was carried out in double distilled water. In Petri plates, weighed amounts of both PEGDA and acrylic acid up to a concentration range of total polymers of about 50% weight/volume (w/v) were dissolved in water and then exposed to ultraviolet radiations at wavelength (λ) of 365 nm for polymerization using a photochemical reactor (Jain Scientific Glasswares, Ambala, India). The hydrogel wafers then were dried and stored in a well-closed container until further use. To study the effect of concentration of such PEGDA cross-linkers on the properties of the hydrogels, hydrogel formulations were prepared with various ratios of PEGDA to the acrylic acid monomer (Table 1).

The prepared hydrogels were purified by soaking the hydrogels in an excess amount of ethanol or ethanol-and-water mixture 12–24 h to remove the soluble impurities. Spectral analysis of the washing medium confirmed the completion of washing.

For easy handling and storage, the purified hydrogels were dried before drug loading. Drying was performed under a hot-air stream flowing over the hydrogel surface using a hot- air sterilizer oven (YSI-431, Yorco, New Delhi, India) at 60 C for 2 h followed by drying in a vacuum oven (Jyoti Scientific, Gwalior, India) at 45 C for 2 h.

Characterization of hydrogels. The physical appearance and texture of the hydrogels were visually evaluated, and their inner morphology was studied using scanning electron microscopy (SEM). The samples were gold-coated and observed under an electron microscope (Leica, Ernst-Leitz-Strasse, Germany) under various magnifications. Glass-transition temperatures of the hydrogels were measured using a differential transition calorimeter (822E, Mettler Toledo, Columbus, Ohio). An aluminum crucible of 40-L capacity held the samples. The samples were heated from 35 C to 350 C at a rate of 10 C/min. Nitrogen gas was used as cooling (at 200 L/min) as well as the purging medium (at 80 L/min).


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