Pearnchob Nantharat, Dashevsky Andrei, Bodmeier Roland
College of Pharmacy, Freie Universität Berlin, Kelchstr. 31, 12169 Berlin, Germany.
J Control Release. 2004 Feb 10;94(2-3):313-21. doi: 10.1016/j.jconrel.2003.10.004.
Shellac is a natural enteric polymer, which results in good gastric resistance; however, it often dissolves too slowly in intestinal fluids. The objective of this study was to improve the disintegration of shellac-coated soft gelatin capsules in simulated intestinal fluids (phosphate buffer pH 6.8) through the addition of pore-formers, such as organic acids and hydrophilic polymers, while retaining gastric resistance. The mechanical properties (% elongation at rupture, puncture strength at break and modulus at puncture), media uptake and weight loss of shellac films were determined upon exposure in 0.1 N HCl and/or phosphate buffer pH 6.8. Organic acids (e.g., sorbic acid) acted as plasticizers, they reduced the glass transition temperature of ethanol-cast shellac films. The addition of additives effectively decreased the disintegration times in phosphate buffer pH 6.8, while the behavior in 0.1 N HCl remained unchanged. In addition, the hardness and disintegration of shellac-coated soft gelatin capsules were monitored through the whole disintegration experiments. The best disintegration was achieved with sorbic acid as pore-former. Sorbic acid remained in the shellac coating at low pH, but leached in pH 6.8 buffer, thus resulting in good gastric resistance and rapid disintegration in simulated intestinal fluids. The disintegration time of ethanolic shellac-coated soft gelatin capsules decreased with increasing amount of pore-former. The slow disintegration of aqueous shellac-coated soft gelatin capsules could be also improved by the addition of hydrophilic polymers, such as hydroxypropyl methylcellulose (HPMC). However, higher HPMC concentrations were required when compared to sorbic acid.
虫胶是一种天然肠溶聚合物，具有良好的抗胃酸能力；然而，它在肠液中的溶解速度通常过慢。本研究的目的是通过添加成孔剂（如有机酸和亲水性聚合物）来提高虫胶包衣软胶囊在模拟肠液（pH 6.8的磷酸盐缓冲液）中的崩解度，同时保持抗胃酸能力。将虫胶膜暴露于0.1 N盐酸和/或pH 6.8的磷酸盐缓冲液中后，测定其机械性能（断裂伸长率、断裂穿刺强度和穿刺模量）、介质吸收和重量损失。有机酸（如山梨酸）起到增塑剂的作用，它们降低了乙醇浇铸虫胶膜的玻璃化转变温度。添加剂的添加有效缩短了在pH 6.8磷酸盐缓冲液中的崩解时间，而在0.1 N盐酸中的行为保持不变。此外，在整个崩解实验过程中监测了虫胶包衣软胶囊的硬度和崩解情况。以山梨酸作为成孔剂时崩解效果最佳。山梨酸在低pH值下保留在虫胶包衣中，但在pH 6.8的缓冲液中溶出，从而在模拟肠液中实现了良好的抗胃酸能力和快速崩解。乙醇溶液包衣的软胶囊的崩解时间随着成孔剂用量的增加而缩短。水性虫胶包衣软胶囊的缓慢崩解也可通过添加亲水性聚合物（如羟丙基甲基纤维素（HPMC））来改善。然而，与山梨酸相比，需要更高的HPMC浓度。
