Objective

The aim of this work was to prepare push-pull osmotic pump capsules using crosslinked hard gelatin capsules as a structural assembly for delivery of four model drugs with different water solubilities including diltiazem hydrochloride, propranolol hydrochloride, ambroxol hydrochloride, and paracetamol.

Methods

A hard gelatin capsule was crosslinked in formaldehyde vapor for 12 h. Then, a push-pull osmotic pump capsule was prepared, and formulation factors were investigated, i.e., the amount and solubility of model drugs, the amount of polyethylene oxide in pull layer, and size of the capsule. Drug release was evaluated to clarify the release characteristic in several release mediums.

Results

Results showed that drug release was independent of drug solubility, drug amount, and capsule size. Almost all of the drug release approached Higuchi’s release model. However, ambroxol hydrochloride could not deliver via this device because of its rather high-density drug particle. Reduction of the polyethylene oxide amount resulted in less drug release. Increasing osmolality of the medium reduced drug release. Drug release studies using a medium with digestive enzymes did not alter drug release compared to medium without enzymes. Push-pull osmotic pump capsules prepared from stored crosslinked hard gelatin capsule shells provided reproducible drug release characteristic.

Conclusion

This developed push-pull osmotic pump capsule is an alternative osmotic pump device for delivery of drugs with different water solubilities.

Graphical Abstract

中文翻译：

---

使用交联的硬明胶胶囊作为结构组件的推拉式渗透泵，用于输送具有不同水溶性的药物

客观的

这项工作的目的是使用交联的硬明胶胶囊作为结构组件来制备推拉式渗透泵胶囊，以递送四种具有不同水溶性的模型药物，包括盐酸地尔硫卓，盐酸普萘洛尔，盐酸氨溴索和扑热息痛。

方法

将硬明胶胶囊在甲醛蒸气中交联12小时。然后，制备了推拉式渗透泵胶囊，并研究了制剂因素，即模型药物的量和溶解度，牵引层中聚环氧乙烷的量以及胶囊的大小。评价药物释放以阐明在几种释放介质中的释放特性。

结果

结果表明，药物释放与药物溶解度，药物量和胶囊大小无关。几乎所有的药物释放都接近Higuchi的释放模型。然而，盐酸氨溴索由于其相当高的药物颗粒而不能通过该装置递送。聚环氧乙烷量的减少导致较少的药物释放。增加介质的重量克分子渗透压浓度会降低药物的释放。与不含酶的培养基相比，使用含消化酶的培养基进行的药物释放研究不会改变药物的释放。由储存的交联的硬明胶胶囊壳制备的推拉渗透泵胶囊提供了可再现的药物释放特性。

结论

这种开发的推拉式渗透泵胶囊是用于输送具有不同水溶性的药物的另一种渗透泵装置。

图形概要