Matsumoto Kohei, Kimura Shin-Ichiro, Iwao Yasunori, Itai Shigeru
Department of Pharmaceutical Engineering and Drug Delivery Science, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
Department of Pharmaceutical Engineering and Drug Delivery Science, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
Int J Pharm. 2017 Oct 30;532(1):528-536. doi: 10.1016/j.ijpharm.2017.09.038. Epub 2017 Sep 18.
Low-melting-point substances are widely used to develop temperature-sensitive formulations. In this study, we focused on microcrystalline wax (MCW) as a low-melting-point substance. We evaluated the drug release behavior of wax matrix (WM) particles using various MCW under various temperature conditions. WM particles containing acetaminophen were prepared using a spray congealing technique. In the dissolution test at 37°C, WM particles containing low-melting-point MCWs whose melting was starting at approx. 40°C (Hi-Mic-1045 or 1070) released the drug initially followed by the release of only a small amount. On the other hand, in the dissolution test at 20 and 25°C for WM particles containing Hi-Mic-1045 and at 20, 25, and 30°C for that containing Hi-Mic-1070, both WM particles showed faster drug release than at 37°C. The characteristic drug release suppression of WM particles containing low-melting-point MCWs at 37°C was thought attributable to MCW melting, as evidenced by differential scanning calorimetry analysis and powder X-ray diffraction analysis. Taken together, low-melting-point MCWs may be applicable to develop implantable temperature-sensitive formulations that drug release is accelerated by cooling at administered site.
低熔点物质被广泛用于开发温度敏感型制剂。在本研究中,我们重点关注微晶蜡(MCW)作为一种低熔点物质。我们在各种温度条件下,使用不同的微晶蜡评估了蜡基质(WM)颗粒的药物释放行为。采用喷雾冷凝技术制备了含对乙酰氨基酚的WM颗粒。在37℃的溶出试验中,含熔点约为40℃开始熔化的低熔点微晶蜡(Hi-Mic-1045或1070)的WM颗粒最初释放药物,随后仅释放少量药物。另一方面,在含Hi-Mic-1045的WM颗粒于20℃和25℃的溶出试验以及含Hi-Mic-1070的WM颗粒于20℃、25℃和30℃的溶出试验中,两种WM颗粒的药物释放均比在37℃时更快。差示扫描量热分析和粉末X射线衍射分析表明,含低熔点微晶蜡的WM颗粒在37℃时具有特征性的药物释放抑制作用,这被认为归因于微晶蜡的熔化。综上所述,低熔点微晶蜡可能适用于开发可植入的温度敏感型制剂,即在给药部位通过冷却加速药物释放。