Coucke D, Pringels E, Foreman P, Adriaensens P, Carleer R, Remon J P, Vervaet C
Laboratory of Pharmaceutical Technology, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium.
Int J Pharm. 2009 Aug 13;378(1-2):45-50. doi: 10.1016/j.ijpharm.2009.05.041. Epub 2009 May 27.
A mucoadhesive spray-dried starch/poly(acrylic acid) powder underwent different heat treatments in order to induce cross-linking between the functional groups of starch (Amioca) and poly(acrylic acid) (Carbopol 974P). After heat treatment the water-absorbing capacity, viscosity and elasticity of the mucoadhesive powder increased. NMR analysis in combination with FT-IR indicated that heat treatment induced a low degree of cross-linking between the polymers. Nasal administration of Amioca/Carbopol 974P powders without heat treatment resulted in an absolute bioavailability in rabbits of 8.2+/-3.0% for insulin. Due to the difference in water-absorbing capacity (which opened the tight junctions of the nasal mucosa), elasticity and plasticity (which reduced mucociliairy clearance and prolonged residence time) heat treatment at 120 degrees C improved the bioavailability: 26.4+/-21.9, 36.5+/-11.0 and 19.3+/-17.3% after heat treatment during 30 min, 1 h and 4 h, respectively. Heat treatment at 60 degrees C was less efficient. This study demonstrated that the nasal insulin absorption improved via heat treatment of the Amioca/Carbopol 974P powder (prior to the addition of insulin). The bioavailability-enhancing effect of a 1 h heat treatment at 120 degrees C was confirmed using the same polymer matrix in combination with different drugs (salmon calcitonin, human growth hormone and metoprolol tartrate).
对一种粘膜粘附性喷雾干燥淀粉/聚丙烯酸粉末进行了不同的热处理，以促使淀粉（木薯淀粉）和聚丙烯酸（卡波姆974P）的官能团之间发生交联。热处理后，粘膜粘附性粉末的吸水能力、粘度和弹性增加。核磁共振分析结合傅里叶变换红外光谱表明，热处理促使聚合物之间发生了低度交联。对未经热处理的木薯淀粉/卡波姆974P粉末进行鼻腔给药，胰岛素在兔体内的绝对生物利用度为8.2±3.0%。由于吸水能力的差异（打开了鼻黏膜的紧密连接）、弹性和可塑性（降低了黏液纤毛清除率并延长了停留时间），120℃的热处理提高了生物利用度：分别在热处理30分钟、1小时和4小时后，生物利用度为26.4±21.9%、36.5±11.0%和19.3±17.3%。60℃的热处理效果较差。本研究表明，通过对木薯淀粉/卡波姆974P粉末进行热处理（在添加胰岛素之前）可改善鼻腔胰岛素吸收。使用相同的聚合物基质与不同药物（鲑鱼降钙素、人生长激素和酒石酸美托洛尔）组合，证实了120℃ 1小时热处理的生物利用度增强效果。
