Department of Pharmaceutics, University of Veterinary and Pharmaceutical Sciences, Palackeho tr. 1946/1, 612 42 Brno, Czech Republic.
Department of Pharmaceutics, University of Veterinary and Pharmaceutical Sciences, Palackeho tr. 1946/1, 612 42 Brno, Czech Republic.
Eur J Pharm Sci. 2019 Apr 30;132:86-95. doi: 10.1016/j.ejps.2019.02.034. Epub 2019 Feb 28.
Due to the additional particle coalescence in the coating, changes in the dissolution profile occur over time in the formulations coated by aqueous ethylcellulose latex. Dry thermal treatment (DT) of the coating can be used as a prevention of this process. Alternatively, it is advisable to take advantage of the synergistic effect of high humidity during wet treatment (WT), which substantially accelerates the film formation. This can be a problem for time-controlled systems, which are based on the coating rupture due to the penetration of water into the core causing the increase in the system volume. This process can begin already during the WT, which may affect the coating adversely. The submitted work was focused on the stability testing of two pellet core compositions: pellets containing swelling superdisintegrant sodium carboxymethyl starch (CMS) and pellets containing osmotically active polyethylene glycol (PEG). Another objective was to identify the treatment/storage condition effects on the pellet dissolution profiles. These pellets are intended to prevent hypoglycemia for patients with diabetes mellitus and therefore, besides the excipients, pellet cores contain 75% or 80% of glucose. The pellet coating is formed by ethylcellulose-based latex, which provides the required lag time (120-360 min). The sample stability was evaluated depending on the pellet core composition (PEG, CMS) for two types of final pellet coating treatment (DT or WT). Scanning electron microscopy and Raman microspectroscopy revealed the penetration of glucose and polyethylene glycol from the core to the PEG pellet surface after WT. For the CMS sample, significant pellet swelling after WT (under the conditions of elevated humidity) was statistically confirmed by the means of stereomicroscopic data evaluation. Therefore, the acceleration of dissolution rate during the stress tests is caused by the soluble substance penetration through the coating in the case of PEG pellets or by dosage form volume increase in the case of CMS pellets. The observed mechanisms can be generally anticipated during the stability testing of the ethylcellulose coated dosage forms. The aforementioned processes do not occur after DT and the pellets are stable in the environment without increased humidity.
由于涂层中的额外颗粒聚集，用水性乙基纤维素乳液涂覆的制剂的溶解曲线会随时间发生变化。涂层的干燥热处理 (DT) 可用作防止此过程的方法。或者，建议利用湿处理 (WT) 期间高湿度的协同作用，这可以大大加速成膜过程。对于基于涂层破裂的时间控制体系来说，这可能是一个问题，因为水的渗透会导致核心进入核心，从而增加系统体积。这个过程可能在 WT 期间就开始了，这可能会对涂层产生不利影响。提交的工作主要集中在两种丸芯成分的稳定性测试上：含有溶胀超级崩解剂羧甲基淀粉钠 (CMS) 的丸芯和含有渗透活性聚乙二醇 (PEG) 的丸芯。另一个目标是确定处理/储存条件对丸芯溶解曲线的影响。这些丸芯旨在预防糖尿病患者的低血糖症，因此除了赋形剂外，丸芯还含有 75%或 80%的葡萄糖。丸芯涂层由基于乙基纤维素的乳液形成，该乳液提供所需的滞后时间（120-360 分钟）。根据丸芯成分（PEG、CMS），评估了两种最终丸芯涂层处理（DT 或 WT）的样品稳定性。扫描电子显微镜和拉曼微光谱显示，WT 后葡萄糖和聚乙二醇从核心渗透到 PEG 丸芯表面。对于 CMS 样品，WT 后（在高湿度条件下）丸芯的明显膨胀通过立体显微镜数据评估得到了统计学上的证实。因此，在应力测试中，PEG 丸芯的溶解速率的加速是由于可溶性物质通过涂层渗透，而 CMS 丸芯的溶解速率的加速是由于制剂体积的增加。在乙基纤维素包衣制剂的稳定性测试中，可以普遍预测到观察到的机制。在 DT 后不会发生上述过程，并且在没有增加湿度的环境中丸芯是稳定的。
