Mady Omar Y, Donia Ahmed A, Al-Shoubki Adam A, Qasim Waseem
Department of Pharmaceutical Technology, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
Department of Pharmaceutical Technology, Faculty of Pharmacy, Menoufia University, Menoufia, Egypt.
Front Pharmacol. 2019 Jul 18;10:713. doi: 10.3389/fphar.2019.00713. eCollection 2019.
Surfactants are well known as permeation enhancers. Span 60 microparticles encapsulating different concentrations of metformin HCl were prepared by using rapid congeal melting technique. Electro-scanning microscope showed smooth surface but less round microparticles. The actual drug content was nearly equal in the different particle sizes of the microparticles. Differential scanning calorimetry results indicated the molecular distribution of the drug molecules with no evidence of drug thermal degradation. The drug release profile from the microparticles has, in each case, burst and there was incomplete drug release. The drug partition coefficient is markedly enhanced as a result of its molecular dispersion in Span 60, indicating the increasing of the drug lipophilicity as a result of its encapsulation in the polar part of the surfactant. Non-everted sac was used to study the drug permeability after solving its critical points. Compared to pure drug, the permeability profile of the drug increased from the Span 60-encapsulated drug, with a total permeation of 68% and drug absorption enhancement of 253%. The drug permeation enhancement mechanism was suggested to be molecular dispersion in the matrix, which is emulsified by Tween 80, and this leads to increasing the hydrophilic paracellular pathway of the drug. Considering the emulsification system of the GIT, which emulsifies the Span 60 instead of Tween 80, a huge improvement of the biopharmaceutics classification system class III permeability and consequently bioavailability could be expected. In addition, this study will open the door to the use of the same technique for enhancing the drug absorption mechanisms by the paracellular pathway for rapid and complete pharmacological effect.
表面活性剂作为渗透促进剂广为人知。采用快速凝融技术制备了包封不同浓度盐酸二甲双胍的司盘60微粒。电子扫描显微镜显示微粒表面光滑但不太圆。不同粒径的微粒中实际药物含量几乎相等。差示扫描量热法结果表明药物分子的分子分布，没有药物热降解的迹象。每种情况下，微粒的药物释放曲线都有突释现象，且药物释放不完全。由于药物分子分散在司盘60中，药物分配系数显著提高，这表明药物包封在表面活性剂的极性部分后亲脂性增加。解决临界点后，采用外翻肠囊法研究药物渗透性。与纯药物相比，包封在司盘60中的药物渗透性曲线有所增加，总渗透率为68%，药物吸收增强253%。药物渗透增强机制被认为是分子分散在基质中，由吐温80乳化，这导致药物亲水性细胞旁路增加。考虑到胃肠道的乳化系统乳化司盘60而非吐温80，预计生物药剂学分类系统III类药物的渗透性及生物利用度将有极大改善。此外，本研究将为采用相同技术通过细胞旁路增强药物吸收机制以实现快速和完全的药理作用打开大门。
