tolfenamic acid

Abstract

The present study deals with the preparation of polyurethane (PU) films impregnated with a nonsteroidal anti-inflammatory drug, tolfenamic acid (TA). Solvent evaporation technique has been employed for the preparation of TA-PU films in two different ratios of 1 : 2 and 1 : 5 in Tetrahydrofuran (THF) or THF-ethanol mixtures. The prepared films were characterized using X-Ray Diffraction (XRD), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and release studies. The results indicate transformation of crystalline TA to its amorphous form. The degree of crystallinity changes both by increasing the polymer concentration and solvent used for the film preparations. The release profiles of TA were also found to be affected, showing a decrease from approximately 50% to 25% from 1 : 2 to 1 : 5 ratios, respectively.

3.1. Appearance of TA-PU Films

Equal volumes of the solutions were used in the preparation of all films. However, TA-PU films prepared by two different methods showed some differences in their appearance. The films prepared by method I (both drug and polymer in THF) were found to be more transparent with smooth surface whereas the films prepared by method II (drug in ethanol and polymer in THF) appeared opaque with slightly rough surface. No signs of recrystallization or changes in appearance took place in all the films during storage for up to 3 months in a desiccator.

3.2.1. XRD Studies

The pure crystalline TA shows characteristic diffraction peaks at 2θ values of 5.21°, 11.58°, 15.72°, 18.70°, 19.77°, 24.90°, 25.32°, 25.90°, and 26.81°, respectively (). In case of PU, a hallow diffraction pattern with no sharp peaks has been observed in the pure as well as in the control films thus indicating its amorphous nature. A typical diffraction pattern has been presented in . The diffraction patterns of the 1 : 2 TA-PU films prepared by method I indicated a marked decrease in the peaks intensity of the crystalline TA and show very small peaks at around 15.72–18.70° and 24.90–26.81° whereas the remaining peaks of the drug have not been detected (). The diffraction pattern of 1 : 5 TA-PU films also shows similar type of result with comparatively less intense peaks in the same region (). This decrease in peak intensity clearly indicates that majority of drug has been transformed to the amorphous form.

3.2.1. XRD Studies

The films prepared using ethanol for drug solubilisation (method II) showed similar type of diffraction patterns for 1 : 2 and 1 : 5 ratios, respectively, but the intensity of the peaks is comparatively higher to the films prepared in THF only (method I) (Figures and ). Therefore, method I could be considered as more effective comparatively in converting crystalline TA to its amorphous form. Similarly, the difference in the diffraction pattern of the films indicates that the solvent also plays an important role in modifying the solid state properties of the drug in addition to the technique used and the nature of the polymer. THF evaporates more rapidly as compared to ethanol-THF mixture [] and therefore the use of THF alone has resulted in greater amorphicity of the drug. The samples were further subjected to analysis by DSC, FTIR, and SEM techniques in order to confirm the results obtained by XRD.