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  • Title: pH-sensitive polymer hydrogels derived from morpholine to prevent the crystallization of ibuprofen.
    Author: Velasco D, Danoux ChB, Redondo JA, Elvira C, San Román J, Wray PS, Kazarian SG.
    Journal: J Control Release; 2011 Jan 20; 149(2):140-5. PubMed ID: 20971143.
    Abstract:
    Various pharmaceutical formulations of ibuprofen are available including oral tablets, suspensions, suppositories and transdermal gels and creams. Aqueous ibuprofen solubility is dependent on pH increasing solubility when increasing pH. The very low aqueous solubility of ibuprofen can lead to a segregation of the drug in to microdomains and possible crystallization which will affect the release profile even leading to possible damage of the mucous membrane of the stomach. Therefore, homopolymers and copolymers of N-ethylmorpholine methacrylamide (EMA) and N, N-dimethylacrylamide (DMA) hydrogels have been prepared to be applied as matrices for ibuprofen release as a method for minimizing these issues. The hydrogels were loaded with ibuprofen and the release over time was tested at 37°C and at different pH values: 2, 5 and 7.4. Fourier-transform infrared spectroscopy with attenuated total reflection (FTIR-ATR) was performed in order to identify the stretching vibrations of the carbonyl group for each component. Dissolution of the ibuprofen from the formulations at different pHs was studied using the ATR-FTIR spectroscopic imaging. The results showed that for DMA hydrogels, most of ibuprofen was released as non crystalline ibuprofen at pH 7.4 but it was not able to prevent crystallization at pH 2 and 5. In contrast, the EMA hydrogels were able to prevent crystallization of the ibuprofen at all pHs. Finally, it was demonstrated that there is a minimum concentration at which the polymer becomes ineffective.
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