College of Pharmacy, Freie Universität Berlin, Kelchstr. 31, 12169, Berlin, Germany.
Pensatech Pharma GmbH, Kelchstr. 31, 12169, Berlin, Germany.
AAPS PharmSciTech. 2018 Jan;19(1):148-154. doi: 10.1208/s12249-017-0825-y. Epub 2017 Jun 20.
The objective of this work was the preparation of osmotic tablets using polymer blends of cellulose acetate butyrate (CAB) or ethylcellulose with ammonio methacrylate copolymer (Eudragit® RL). The advantage of these coatings in comparison to the traditionally used cellulose acetate is their solubility in safer organic solvents like ethanol. Polymer films were characterized with respect to their water uptake, dry mass loss, and mechanical properties. The effect of the polymer blend ratio on drug release and on the rupture force of the coating was investigated. In addition, the effect of drug solubility and content, pH and agitation rate of the release medium, and coating level and plasticizer content on the release were studied. With increased Eudragit® RL content in the coating blends, higher medium uptake of the film was observed, resulting in shorter lag times and faster drug release from the osmotic tablets. Replacing ethylcellulose with cellulose acetate butyrate as a coating material led to shorter lag times and faster drug release due to increased film permeability. In addition, CAB-based films had a higher strength and flexibility. The drug release was osmotically controlled and decreased with increasing coating level. It increased with increased drug solubility, plasticizer content, change of buffer species (acetate > phosphate), and decreased coating level. Agitation rate and drug content had no effect on the drug release. A 20% w/w coating level was sufficient for the tablet to tolerate forces of more than five times of the gastric destructive force reported in literature.
这项工作的目的是制备使用醋酸丁酸纤维素（CAB）或乙基纤维素与氨甲基丙烯酸共聚物（Eudragit® RL）的聚合物共混物的渗透片剂。与传统使用的醋酸纤维素相比，这些涂层的优势在于它们在乙醇等更安全的有机溶剂中的溶解度。对聚合物薄膜的水吸收、干质量损失和机械性能进行了表征。研究了聚合物共混物比例对药物释放和涂层破裂力的影响。此外，还研究了药物溶解度和含量、释放介质的 pH 值和搅拌速度、涂层水平和增塑剂含量对释放的影响。随着涂层共混物中 Eudragit® RL 含量的增加，观察到膜对介质的吸收增加，导致滞后时间缩短，渗透片剂中的药物释放加快。用醋酸丁酸纤维素代替乙基纤维素作为涂层材料，由于膜的渗透性增加，导致滞后时间缩短，药物释放加快。此外，CAB 基薄膜具有更高的强度和柔韧性。药物释放是渗透控制的，随着涂层水平的增加而降低。随着药物溶解度、增塑剂含量、缓冲剂种类（醋酸盐>磷酸盐）的增加和涂层水平的降低而增加。搅拌速度和药物含量对药物释放没有影响。20%w/w 的涂层水平足以使片剂承受文献报道的胃破坏性力的五倍以上的力。
