Improvement of the Dissolution Rate of Indomethacin by a Cogrinding Technique using Polyethylene Glycols of Various Molecular Weights

Shokri, Javad and Hanaee, J. and Barzegar-Jalali, Mohammad and Changizi, R. and Rahbar, M. and Nokhodchi, Ali (2006) Improvement of the Dissolution Rate of Indomethacin by a Cogrinding Technique using Polyethylene Glycols of Various Molecular Weights. Journal of Drug Delivery Science and Technology, 16 (3). pp. 203-209. ISSN 1773-2247 (ISSN). (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Indomethacin is an anti inflammatory drug which is used to relieve pain and inflammatory conditions. For poorly soluble drugs and highly permeable drugs such as indomethacin, the rate of oral absorption is often controlled by the dissolution rate in the gastrointestinal tract. Therefore together with the permeability, the solubility and dissolution behaviour of a drug are key determinants of its oral bioavailability. In this study, an attempt was made to enhance the dissolution rate of indomethacin using various molecular weights of polyethylene glycol (PEG2000, 6000 and 20000) by a cogrinding technique. The cogrinds containing different drug:PEG ratios (1:1, 1:2, 1:5, 1:10) were made and the dissolution rate of the drug from each of the formulations was studied at different pHs (1.2, 4.6 and 6.8). The results showed a significant increase in the dissolution rate of indomethacin at various pHs from cogrinds formulations, obtained by this cogrinding technique, in comparison to that of the pure drug powder, treated pure drug, or physical mixtures at all studied pHs. The dissolution results did not show significant differences between the dissolution rates of indomethacin from cogrinds containing PEG2000 with various drug:carrier ratios, whereas these differences were considerably significant for the cogrinds samples containing PEG20000. These results confirm that the dominant mechanism of low molecular weights of PEGs in increasing the indomethacin dissolution rate from cogrinds is the formation of a thin film of the PEG around the poorly soluble drug particles. In the case of high molecular weight PEGs, such as PEG20000, since the indomethacin:carrier ratios significantly affected the dissolution rate of indomethacin from the cogrinds, therefore, it seems that the increase in dissolution of indomethacin from these cogrinds was mainly caused by an improved solubility of the drug by the presence of these carriers. The particle size analysis showed small changes in the particle size diameter and powder surface area of indomethacin after grinding (16.3% reduction in median particle diameter and 18.8% increase in the total powder surface area). The XRD and FTIR spectra rejected any polymorphic changes or the production of amorphous indomethacin due to the cogrinding process. These spectra showed only slight changes in the crystal orientation after milling.

Item Type: Article
Subjects: Q Science
Divisions: Faculties > Science Technology and Medical Studies > Medway School of Pharmacy
Depositing User: Ali Nokhodchi
Date Deposited: 10 Sep 2008 14:02
Last Modified: 17 Jul 2014 14:09
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