Mady Omar Y, Abulmeaty Mahmoud M A, Donia Ahmed A, Al-Khureif Abdulaziz A, Al-Shoubki Adam A, Abudawood Manal, Abdel Moety Doaa A
Department of Pharmaceutical Technology, Faculty of Pharmacy, Tanta University, Tanta 31511, Egypt.
Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia.
Membranes (Basel). 2021 Aug 26;11(9):659. doi: 10.3390/membranes11090659.
Candesartan cilexetil (CC) is an antihypertensive drug. It has low solubility and faces hepatic first-pass metabolism after oral ingestion. We formulated bioadhesive buccal films and studied the respective drug pharmacokinetics. Different bioadhesive films were prepared (40, 80, 120, 160, 200, and 240 mg CC per film) by using the solvent casting method. The drug concentrations used affect the drug entrapment mechanism, which was reflected in the film physicochemical properties like thickness, weight, drug content, bioadhesion, and drug release. Low drug concentration (F2, 40 mg per film) led to minute drug crystal dispersion while increasing the drug concentration (F7, 240 mg per film) showed drug crystal encapsulation, which affects the drug release. The drug pharmacokinetic from the prepared films was studied compared to the oral form by serial blood sampling via an inserted catheter in the carotid of rats. High-Performance Liquid Chromatography assay was used to measure the plasma concentration of CC in different forms. Compared to other films, the F2 showed the highest maximal concentration (Cmax) and the lowest elimination half-life (t). Bioadhesion buccal film of CC has better bioavailability, especially at low concentrations. The ease, robustness, and ruggedness of the preparation suggests the same procedure for drugs like CC.
坎地沙坦酯（CC）是一种抗高血压药物。它的溶解度低，口服后会面临肝脏首过代谢。我们制备了生物黏附性口腔膜并研究了相应的药物药代动力学。采用溶剂浇铸法制备了不同的生物黏附膜（每片含CC 40、80、120、160、200和240 mg）。所使用的药物浓度会影响药物包封机制，这反映在膜的物理化学性质上，如厚度、重量、药物含量、生物黏附性和药物释放。低药物浓度（F2，每片40 mg）导致药物微晶分散，而增加药物浓度（F7，每片240 mg）则显示药物晶体包封，这会影响药物释放。通过在大鼠颈动脉插入导管进行连续采血，研究了所制备膜剂与口服剂型相比的药物药代动力学。采用高效液相色谱法测定不同剂型CC的血浆浓度。与其他膜相比，F2显示出最高的最大浓度（Cmax）和最低的消除半衰期（t）。CC生物黏附性口腔膜具有更好的生物利用度，尤其是在低浓度时。该制剂的简便性、稳健性和耐用性表明CC等药物可采用相同的制备方法。
