Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Egypt.
J Adv Res. 2014 May;5(3):347-56. doi: 10.1016/j.jare.2013.05.005. Epub 2013 Jun 11.
The aim of this study was to develop and optimize Trimetazidine dihydrochloride (TM) controlled porosity osmotic pump (CPOP) tablets of directly compressed cores. A 2(3) full factorial design was used to study the influence of three factors namely: PEG400 (10% and 25% based on coating polymer weight), coating level (10% and 20% of tablet core weight) and hole diameter (0 "no hole" and 1 mm). Other variables such as tablet cores, coating mixture of ethylcellulose (4%) and dibutylphthalate (2%) in 95% ethanol and pan coating conditions were kept constant. The responses studied (Yi ) were cumulative percentage released after 2 h (Q%2h), 6 h (Q%6h), 12 h (Q%12h) and regression coefficient of release data fitted to zero order equation (RSQzero), for Y 1, Y 2, Y 3, and Y 4, respectively. Polynomial equations were used to study the influence of different factors on each response individually. Response surface methodology and multiple response optimization were used to search for an optimized formula. Response variables for the optimized formula were restricted to 10% ⩽ Y 1 ⩽ 20%, 40% ⩽ Y 2 ⩽ 60%, 80% ⩽ Y 3 ⩽ 100%, and Y 4 > 0.9. The statistical analysis of the results revealed that PEG400 had positive effects on Q%2h, Q%6h and Q%12h, hole diameter had positive effects on all responses and coating level had positive effect on Q%6h, Q%12h and negative effect on RSQzero. Full three factor interaction (3FI) equations were used for representation of all responses except Q%2h which was represented by reduced (3FI) equation. Upon exploring the experimental space, no formula in the tested range could satisfy the required constraints. Thus, direct compression of TM cores was not suitable for formation of CPOP tablets. Preliminary trials of CPOP tablets with wet granulated cores were promising with an intact membrane for 12 h and high RSQzero. Further improvement of these formulations to optimize TM release will be done in further studies.
本研究旨在开发和优化曲美他嗪二盐酸盐（TM）控释渗透泵（CPOP）直接压片芯。采用 2(3)完全因子设计研究了三个因素的影响：聚乙二醇 400（基于包衣聚合物重量的 10%和 25%）、包衣水平（片剂芯重量的 10%和 20%）和孔径（0“无孔”和 1 毫米）。其他变量，如片剂芯、乙基纤维素（4%）和邻苯二甲酸二丁酯（2%）在 95%乙醇中的包衣混合物和锅包衣条件保持不变。研究的响应（Yi）分别为 2 小时（Q%2h）、6 小时（Q%6h）、12 小时（Q%12h）后的累积释放百分比和拟合零级方程（RSQzero）的释放数据的回归系数（Y1、Y2、Y3 和 Y4）。使用多项式方程研究不同因素对每个响应的单独影响。响应面法和多响应优化用于搜索优化配方。优化配方的响应变量限于 10%≤Y1≤20%、40%≤Y2≤60%、80%≤Y3≤100%和 Y4>0.9。结果的统计分析表明，PEG400 对 Q%2h、Q%6h 和 Q%12h 有积极影响，孔径对所有响应有积极影响，包衣水平对 Q%6h、Q%12h 有积极影响，对 RSQzero 有消极影响。除 Q%2h 外，所有响应均采用完整三因子相互作用（3FI）方程表示，Q%2h 采用简化（3FI）方程表示。在探索实验空间时，在所测试范围内，没有配方能够满足所需的约束。因此，TM 芯的直接压缩不适合形成 CPOP 片剂。用湿法制粒芯制成的 CPOP 片剂的初步试验很有希望，能保持完整的膜 12 小时，RSQzero 高。在进一步的研究中，将对这些制剂进行进一步改进，以优化 TM 的释放。
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