Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari, Universita degli Studi di Palermo, Italy.
Curr Pharm Des. 2012;18(34):5405-10. doi: 10.2174/138161212803307563.
The aim of this study was to investigate the potential for systemic administration of Methimazole (MMI) through the buccal mucosa as an alternative route for drug delivery. Considering that the most important restriction in buccal drug delivery could be the low permeability of the mucosa, the ability of MMI to cross the mucosal barrier was assessed. Permeation of MMI through porcine buccal mucosa was investigated ex vivo using Franz type diffusion cells, buffer solution simulating saliva or natural human saliva as donor phase. The collected data suggested that buccal mucosa does not hinder MMI diffusion and the drug crosses the membrane (J(s) = 0.068 mg cm(-2) h(-1) and K(p) = 0.065 cm h(-1)). Matrix tablets, suitable for administration on buccal mucosa, were then designed and prepared by direct compression of MMI loaded matrices (70% w/w) using Eudragit(®) RS 100 as a matrixing, low permeable, pH-independent, mucoadhesive and insoluble agent. The matrix tablets were evaluated in vitro for dissolution; however, the drug was discharged too rapidly from tablets. To obtain drug release rate suitable to maintain constant drug levels in the central compartment the tablets were coated with lipophilic material (glycerol tristearate). In ex vivo permeation experiments, therapeutically MMI plasma levels were obtained when matrix tablets were coated with 0.10 mm thick lipophilic coating film. Coated tablets placed on buccal porcine mucosa provide optimal drug release rate. Coated buccal matrix tablets may represent a potential alternative dosage form for systemic delivery of MMI in hyperthyroidism management.
本研究旨在探索通过颊黏膜系统给药作为药物传递替代途径的可能性。鉴于颊腔给药最重要的限制可能是黏膜的低渗透性，评估了甲巯咪唑（MMI）穿越黏膜屏障的能力。使用 Franz 型扩散池体外研究 MMI 通过猪颊黏膜的渗透，使用模拟唾液或天然人唾液的缓冲液作为供体相。收集的数据表明颊黏膜不会阻碍 MMI 的扩散，药物穿过膜（J（s）= 0.068 mg cm(-2) h(-1)和 K(p) = 0.065 cm h(-1)）。然后通过直接压缩负载 MMI 的基质（70%w/w），使用 Eudragit(®) RS 100 作为基质、低渗透性、pH 无关、黏膜黏附性和不溶性的赋形剂，设计并制备适合颊黏膜给药的基质片。对基质片进行体外溶解评估；然而，药物从片剂中迅速排出。为了获得适合维持中央隔室中药物水平恒定的药物释放率，将片剂用亲脂性材料（三硬脂酸甘油酯）包衣。在体外渗透实验中，当基质片用 0.10 毫米厚的亲脂性包衣膜包衣时，可获得治疗性 MMI 血浆水平。置于颊腔猪黏膜上的包衣片剂可提供最佳的药物释放率。包衣颊腔基质片可能是治疗甲状腺功能亢进症管理中 MMI 全身给药的潜在替代剂型。
