Lin Ying Ku, Ho Hsiu O
Graduate Institute of Pharmaceutical Sciences, Taipei Medical University, 250 Wu-Hsing Street, 110, ROC, Taipei, Taiwan.
J Control Release. 2003 Apr 14;89(1):57-69. doi: 10.1016/s0168-3659(03)00091-9.
Asymmetric membrane-coated capsules with in situ formation of a delivery orifice were examined for their improved osmotic effects. The release mechanisms were investigated for drugs with both moderate to high water solubility and those with poor water solubility. The capsule wall membrane was produced by a phase-inversion process, in which an asymmetric membrane was formed on stainless steel mold pins by dipping the mold pins into a coating solution containing a polymeric material followed by dipping into a quenching solution. In situ formation of a delivery orifice in the thin membrane was proven by visualization of a jet stream of chlorophyll being released from the capsule. The release mechanism for drugs with moderate to high water solubility was mainly controlled by the osmotic effect, which is a function of the drug's solubility. Permeability across the asymmetric membrane of the capsule was determined to be 4.28 x 10(-6) cm(2)/h-atm at 37 degrees C for drugs with water solubilities in a moderate to high range. Accordingly, the poorly water-soluble drug, nifedipine, was unable to create enough of an osmotic effect to activate drug release. Solubilization either by the addition of the solubility enhancer, SLS, or by a solid dispersion with HPMC could increase the solubility of nifedipine to a sufficient extent to activate drug release. It was found that the suspending ability induced by the viscous nature of HPMC further interacted with SLS to synergistically increase the maximal percent release and the release rate of nifedipine. The osmotic effect of this suspension ability was proposed as the underlying mechanism responsible for the release of poorly water-soluble drugs, i.e. nifedipine, from this system.
对具有原位形成给药孔的不对称膜包衣胶囊的改善渗透效果进行了研究。研究了具有中等到高水溶性的药物以及水溶性差的药物的释放机制。胶囊壁膜通过相转化过程制备，其中通过将不锈钢模具针浸入含有聚合物材料的包衣溶液中，然后浸入淬火溶液中，在模具针上形成不对称膜。通过观察从胶囊中释放的叶绿素喷射流，证明了在薄膜中原位形成给药孔。中等到高水溶性药物的释放机制主要受渗透作用控制，渗透作用是药物溶解度的函数。对于水溶性在中等到高范围内的药物，在37℃下测定其穿过胶囊不对称膜的渗透率为4.28×10(-6) cm(2)/h-atm。因此，水溶性差的药物硝苯地平无法产生足够的渗透作用来激活药物释放。通过添加增溶剂SLS或与HPMC形成固体分散体来增溶，可以将硝苯地平的溶解度提高到足以激活药物释放的程度。发现由HPMC的粘性性质引起的悬浮能力进一步与SLS相互作用，协同增加硝苯地平的最大释放百分比和释放速率。这种悬浮能力的渗透作用被认为是负责从该系统中释放水溶性差的药物（即硝苯地平）的潜在机制。
