Ramanathan Surash, Parthasarathy Suhanya, Murugaiyah Vikneswaran, Magosso Enrico, Tan Soo Choon, Mansor Sharif Mahsufi
Centre for Drug Research, Universiti Sains Malaysia, Penang 11800, Malaysia.
School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia.
Molecules. 2015 Mar 18;20(3):4915-27. doi: 10.3390/molecules20034915.
Varied pharmacological responses have been reported for mitragynine in the literature, but no supportive scientific explanations have been given for this. These studies have been undertaken without a sufficient understanding of the physicochemical properties of mitragynine. In this work a UV spectrophotometer approach and HPLC-UV method were employed to ascertain the physicochemical properties of mitragynine. The pKa of mitragynine measured by conventional UV (8.11 ± 0.11) was in agreement with the microplate reader determination (8.08 ± 0.04). Mitragynine is a lipophilic alkaloid, as indicated by a logP value of 1.73. Mitragynine had poor solubility in water and basic media, and conversely in acidic environments, but it is acid labile. In an in vitro dissolution the total drug release was higher for the simulated gastric fluid but was prolonged and incomplete for the simulated intestinal fluid. The hydrophobicity, poor water solubility, high variability of drug release in simulated biological fluids and acid degradable characteristics of mitragynine probably explain the large variability of its pharmacological responses reported in the literature. The determined physicochemical properties of mitragynine will provide a basis for developing a suitable formulation to further improve its solubility, stability and oral absorption for better assessment of this compound in preclinical studies.
文献中已报道了美他加宁的多种药理反应，但对此尚无支持性的科学解释。这些研究是在对美他加宁的物理化学性质缺乏充分了解的情况下进行的。在这项工作中，采用紫外分光光度计法和高效液相色谱 - 紫外法来确定美他加宁的物理化学性质。通过常规紫外法测得的美他加宁的pKa值为(8.11 ± 0.11)，与酶标仪测定值(8.08 ± 0.04)一致。美他加宁是一种亲脂性生物碱，其logP值为1.73表明了这一点。美他加宁在水和碱性介质中的溶解度较差，相反在酸性环境中溶解度较好，但它对酸不稳定。在体外溶出试验中，模拟胃液中的总药物释放较高，但模拟肠液中的释放时间延长且不完全。美他加宁的疏水性、水溶性差、在模拟生物流体中药物释放的高度变异性以及酸可降解特性可能解释了文献中报道的其药理反应的巨大变异性。所确定的美他加宁的物理化学性质将为开发合适的制剂提供依据，以进一步提高其溶解度、稳定性和口服吸收，从而在临床前研究中更好地评估该化合物。
