Mazurek-Wadołkowska Edyta, Winnicka Katarzyna, Czyzewska Urszula, Miltyk Wojciech
Acta Pol Pharm. 2016 Jul;73(4):1029-1036.
High profitability and simplicity of direct compression, encourages pharmaceutical industry to create universal excipients to improve technology process. Prosolv® SMCC - silicified microcrystalline cellulose and Starch 1500® - pregelatinized starch, are the example of multifunctional excipients. The aim of the present study was to evaluate the stability of theophylline (API) in the mixtures with excipients with various physico-chemical properties (Prosolv® SMCC 90, Prosolv® SMCC HD 90, Prosolv* SMCC 50®, Starch 1500® and magnesium stearate). The study presents results of thermal analysis of the mixtures with theophylline before and after 6 months storage of the tablets at various temperatures and relative humidity conditions (25 ± 2°C/40 ± 5% RH, 40 ± 2°C/75 ± 5% RH). It was shown that high concentration of Starch 1500® (49%) affects the stability of the theophylline tablets with Prosolv® SMCC. Prosolv® SMCC had no effect on API stability as confirmed by the differential scanning calorimetry (DSC). Changes in peak placements were observed just after tabletting process, which might indicate that compression accelerated the incompatibilities between theophylline and Starch 1500. TGA analysis showed loss in tablets mass equal to water content in starch. GC-MS study established no chemical decomposition of theophylline. We demonstrated that high content of Starch 1500® (49%) in the tablet mass, affects stability on tablets containing theophylline and Prosolv® SMCC.
直接压片的高利润率和简便性，促使制药行业研发通用辅料以改进工艺流程。Prosolv® SMCC（硅化微晶纤维素）和Starch 1500®（预胶化淀粉）就是多功能辅料的例子。本研究的目的是评估茶碱（活性药物成分）与具有不同物理化学性质的辅料（Prosolv® SMCC 90、Prosolv® SMCC HD 90、Prosolv* SMCC 50®、Starch 1500®和硬脂酸镁）混合物的稳定性。该研究展示了在不同温度和相对湿度条件（25 ± 2°C/40 ± 5% RH、40 ± 2°C/75 ± 5% RH）下，片剂储存6个月前后，茶碱混合物的热分析结果。结果表明，高浓度（49%）的Starch 1500®会影响含Prosolv® SMCC的茶碱片剂的稳定性。差示扫描量热法（DSC）证实Prosolv® SMCC对活性药物成分的稳定性没有影响。在压片过程刚结束后就观察到峰位置的变化，这可能表明压片加速了茶碱与Starch 1500之间的不相容性。热重分析（TGA）显示片剂质量损失等于淀粉中的水分含量。气相色谱 - 质谱联用（GC - MS）研究表明茶碱没有化学分解。我们证明了片剂中高含量（49%）的Starch 1500®会影响含茶碱和Prosolv® SMCC片剂的稳定性。
