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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Conclusion

Generally, in case of cross-linking agents such as divinyl glycol, divinyl benzene, or tripropyleneglycol diacrylate, an increase in cross-linking density is known to reduce the equilibrium swelling (35, 36). In this study, where polyethylene diacrylate (PEDGA) was used as cross-linker, an increase in equilibrium swelling was observed with the increase in the amount of PEGDA. This change may be from PEGDA as it is a water-retaining compound. Because it is serving as a copolymer in the present hydrogel system, the properties of PEGDA affects the properties of these copolymeric hydrogels. The diffusion coefficient and drug-release rate, however, followed the general trend: An increase in the amount of PEGDA reduced the diffusion coefficient and release rate because of an increase in cross-linking density. Apart from the cross-linking density, in this study the larger amounts of cross-linker PEGDA, having somewhat higher affinity for water, made the diffusion a little more difficult. In all the experiments, for the similar weight composition, the increase in molecular weight of PEG led to a decrease in the water-imbibing capacity and drug-loading capacity of the hydrogels because of the reduction in hydrophilicity of the system.

The diffusion coefficient and drug-release rate, however, increased with the increase in molecular weight. These results also were related to the porosity of the hydrogels. The porosity of the hydrogels decreased with an increase of the amount of PEGDA and increased with an increase in molecular weight. This change may be from a significant reduction in molecular availability of poly(ethylene glycol) cross-linkers in the polyacrylate hydrogel matrix. The chemical representation of the hydrogels made up of different molecular weight PEGDA (see Figure 4) also supported this assumption of the porosity of hydrogels.

Acknowledgment

The authors acknowledge the University Grants Commission (New Delhi, India) and the Council of Scientific and Industrial Research (New Delhi, India) for funding the research projects as fellowship grants to some of the authors. The authors extend their deep gratitude to Electron Microscopy Division of All India Institute of Medical Sciences (New Delhi, India), Sun Pharmaceuticals (Baroda, India) and SAIF-RSIC, Central Drug Research Institute (CDRI) (Lucknow, India) for extending their instrumentation facilities for the purpose of the sample analysis.

Sulekha Bhadra,PhD, and Dipankar Bhadra, PhD, are research officers in Sun Pharma's Advanced Research Center, Vadodara, India. Govind Prasad Agrawal* is a professor, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar, Madhya Pradesh, India, 470003, tel. + 91 7582 265457,

*To whom all correspondence should be addressed.

Submitted: Feb. 20, 2006. Accepted: Aug. 28, 2006.

Key words: acrylate, copolymer, diclofenac, hydrogels, PEG

References

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2. L.B. Peppas, "Preparation and Characterization of Crosslinked Hydrophilic Networks," in Absorbent Polymer Technology, L.B. Peppas and R.S. Harland, Eds. (Elsevier, Amsterdam, 1990), pp. 45–66.

3. A.S. Hickey and N.A. Peppas, "Mesh Size and Diffusive Characteristics of Semicrystalline Polyvinyl Alcohol Membranes Preparation by Freezing/Thawing Technology," J. Membrane Sc. 107 (3), 229–237 (1995).

4. N.A. Peppas and N.K. Mongia, "Ultrapure Polyvinyl Alcohol Hydrogels with Mucoadhesive Drug Delivery Characteristics," Eur. J. Pharm. Biopharm. 43 (1), 51–58 (1997).

5. W.E. Hennink and C.E. von Nustrum, "Novel Crosslinking Methods in Design of Hydrogels," Adv Drug Del. Rev, 54 (1), 13–36 (2002).

6. H. Park and K. Park, in Hydrogels and Biodegradable Polymers for Bioapplications, R.M. Ottenbrite, S.J. Huang and K. Park, Eds. (American Chemical Society, Washington, D.C., 1996), pp. 1–10.

7. N.A. Peppas, "Hydrogels and Drug Delivery," Curr. Opin. Coll. Int. Sci. 2, 531–537 (1997).


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