Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, Mississippi, 38677, USA.
Thermo Fisher Scientific, Tewksbury, Massachusetts, 01876, USA.
AAPS PharmSciTech. 2017 Oct;18(7):2639-2647. doi: 10.1208/s12249-017-0728-y. Epub 2017 Feb 28.
As the buccal route of administration has the ability to avoid the GI tract and first-pass effect by directing the absorption toward the cheek area, the bioavailability of BCS class III drugs can be increased through this route. Only a handful of studies have been conducted using oleic acid as a permeation enhancer in any transbuccal drug delivery system. Therefore, the objectives of this novel study were to develop a buccal tablet using two concentrations of oleic acid for a model BCS class III drug via hot-melt extrusion technology and to investigate the effects of oleic acid on the physicochemical properties of the tablet. The model drug selected was ondansetron hydrochloride. Formulations consisting of polymers (hydroxypropyl methylcellulose and polyethylene oxide) and two concentrations of oleic acid were prepared by hot-melt extrusion techniques. A melting point depression of the drug was obtained in the extruded granules as seen by the DSC thermograms. The ex vivo permeation studies showed a greater permeation of the drug in the formulation containing 10% oleic acid (F2) as compared to the formulation containing 20% oleic acid (F1), although not statistically significant. The in vitro bioadhesion studies, swelling studies, and surface pH measurements of the tablets were also conducted. In conclusion, permeation studies exhibited the potential of oleic acid as a buccal permeation enhancer as a significant permeation of the drug was obtained in the formulations. Hot-melt extrusion technology was successfully employed to formulate buccal tablets of ondansetron hydrochloride.
由于口腔给药途径能够通过将吸收导向脸颊区域来避免胃肠道和首过效应，因此可以通过该途径提高 BCS 类 III 药物的生物利用度。只有少数研究已经使用油酸作为任何口腔药物传递系统中的渗透增强剂进行。因此，本新型研究的目的是通过热熔挤出技术为模型 BCS 类 III 药物开发使用两种浓度油酸的口腔片剂，并研究油酸对片剂理化性质的影响。选择的模型药物是盐酸昂丹司琼。由聚合物（羟丙基甲基纤维素和聚氧化乙烯）和两种浓度油酸组成的配方通过热熔挤出技术制备。如 DSC 热谱图所示，挤出颗粒中药物的熔点降低。体外渗透研究表明，与含有 20%油酸的配方（F1）相比，含有 10%油酸的配方（F2）中药物的渗透更大，尽管没有统计学意义。还进行了片剂的体外生物黏附研究、溶胀研究和表面 pH 值测量。总之，渗透研究表明油酸作为口腔渗透增强剂具有潜力，因为在配方中获得了药物的显著渗透。成功地使用热熔挤出技术来配制盐酸昂丹司琼的口腔片剂。
