Ibrahim Mohamed Abbas, Alshora Doaa Hasan
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Polymers (Basel). 2021 Nov 21;13(22):4034. doi: 10.3390/polym13224034.
Aceclofenac (AC) is a nonsteroidal anti-inflammatory drug used in the treatment of chronic pain in conditions such as rheumatoid arthritis, with frequent administration during the day. The formulation of sustained release matrix pellets can provide a promising alternative dosage form that controls the release of the drug, with less blood fluctuation and side effects-especially those related to the gastric system. The extrusion/spheronization technique was used to formulate AC matrix pellets. The response surface methodology (version 17.2.02.; Statgraphics Centurion) was used to study the impacts of Eudragit RL 100 and PVP K90 binder solution concentrations on the pellets' wet mass peak torque, pellet size, and the release of the drug. Statistically, a significant synergistic effect of PVP K90 concentration on the peak torque and pellet size was observed ( = 0.0156 and 0.031, respectively), while Eudragit RL 100 showed significant antagonistic effects ( = 0.042 and 0.013, respectively). The peak torque decreased from 0.513 ± 0.022 to 0.41 ± 0.021 when increasing the Eudragit RL 100 from 0 to 20%, and the pellet size decreased from 0.914 ± 0.047 to 0.789 ± 0.074 nm. The tested independent factors did not significantly affect the drug release in the acidic medium within 2 h, but these pellet formulae maintained the drug release at less than 10% in the acidic medium (pH 1.2), which may decrease gastric irritation side effects. In contrast, a highly significant synergistic effect of Eudragit and highly antagonistic effect of the PVP solution on drug release in the alkaline-pH medium were observed ( = 0.002 and 0.007, respectively). The optimized pellet formula derived from the statistical program, composed of 3.21% Eudragit and 5% PVP solution, showed peak torque of 0.861 ± 0.056 Nm and pellet size of 1090 ± 85 µm, and resulted in a significant retardation effect on the release after 8 h compared to the untreated drug.
醋氯芬酸（AC）是一种非甾体抗炎药，用于治疗类风湿性关节炎等病症中的慢性疼痛，需在白天频繁给药。缓释基质微丸制剂可提供一种有前景的替代剂型，能控制药物释放，减少血药波动和副作用，尤其是与胃系统相关的副作用。采用挤出/滚圆技术制备AC基质微丸。运用响应面法（版本17.2.02；Statgraphics Centurion）研究了Eudragit RL 100和聚乙烯吡咯烷酮K90（PVP K90）粘合剂溶液浓度对微丸湿质量峰值扭矩、微丸尺寸和药物释放的影响。从统计学角度看，观察到PVP K90浓度对峰值扭矩和微丸尺寸有显著协同效应（分别为P = 0.0156和0.031），而Eudragit RL 100显示出显著拮抗效应（分别为P = 0.042和0.013）。当Eudragit RL 100从0增加到20%时，峰值扭矩从0.513±0.022降至0.41±0.021，微丸尺寸从0.914±0.047降至0.789±0.074 nm。所测试的独立因素在2小时内对酸性介质中的药物释放无显著影响，但这些微丸配方在酸性介质（pH 1.2）中药物释放维持在10%以下，这可能会降低胃部刺激副作用。相比之下，观察到Eudragit对碱性pH介质中药物释放有高度显著协同效应，而PVP溶液有高度拮抗效应（分别为P = 0.002和0.007）。由统计程序得出的优化微丸配方，由3.21%的Eudragit和5%的PVP溶液组成，峰值扭矩为0.861±0.056 Nm，微丸尺寸为1090±85 µm，与未处理药物相比，在8小时后对释放产生了显著的延迟作用。
