Department of Materials Science and Engineering, The Kroto Research Institute, University of Sheffield, North Campus, Broad Lane, Sheffield, S3 7HQ, UK.
AAPS PharmSciTech. 2013 Jun;14(2):870-9. doi: 10.1208/s12249-013-9974-9. Epub 2013 Apr 27.
Solid-state properties of tolfenamic acid (TA) and its complexes with chitosan (CT) have been studied. Effect of medium pH, molecular weight of polymer and its different concentrations on these TA-CT complexes were studied in detail. Low and medium molecular weight CT have been used in different ratios at pH ranging from 4 to 6 and freeze-drying technique has been employed to modify the appearance of crystalline TA. Physical properties of the formed complexes have been studied by employing X-ray diffraction, differential scanning calorimetry and scanning electron microscopy; chemical structure has been studied using Fourier transform infrared spectroscopy. The results showed that both forms of the polymer exhibited complete conversion in 1:8 ratio at pH 4, 1:4 at pH 5 and 1:1 at pH 6 indicating a marked effect of pH on drug-polymer complexation. The percent crystallinity calculations indicated low molecular weight CT slightly more effective than the other form. No changes in the complexes have been observed during the 12 week storage under controlled conditions. Both forms of CT at different pH values indicated retardation of recrystallization in TA during cooling of the melt from 1:1 ratios exhibiting formation of strong intermolecular hydrogen bonding between the drug and the polymer.
已研究了托芬那酸（TA）及其与壳聚糖（CT）复合物的固态性质。详细研究了介质 pH 值、聚合物分子量及其不同浓度对这些 TA-CT 复合物的影响。在 pH 值为 4 至 6 范围内，使用了不同比例的低分子量和中等分子量 CT，并采用冷冻干燥技术来改变结晶 TA 的外观。通过 X 射线衍射、差示扫描量热法和扫描电子显微镜研究了形成的复合物的物理性质；使用傅里叶变换红外光谱研究了化学结构。结果表明，在 pH 值为 4 时，两种形式的聚合物在 1:8 的比例下完全转化，在 pH 值为 5 时为 1:4，在 pH 值为 6 时为 1:1，表明 pH 值对药物-聚合物络合有明显影响。结晶度计算表明，低分子量 CT 比另一种形式稍微有效。在控制条件下储存 12 周期间，复合物没有发生变化。在冷却熔融物从 1:1 比例时，两种形式的 CT 在不同 pH 值下均表明 TA 中再结晶的延迟，表现为药物和聚合物之间形成强的分子间氢键。
