通过基于聚氧乙烯蓖麻油（®）的液固分散体片剂提高盐酸非索非那定的口服生物利用度
Enhancement of the Oral Bioavailability of Fexofenadine Hydrochloride via Cremophor(®) El-Based Liquisolid Tablets.
作者信息
Yehia Soad Ali, El-Ridi Mohamed Shafik, Tadros Mina Ibrahim, El-Sherif Nolwa Gamal
机构信息
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Department of Pharmaceutical Technology, National Research Center, Dokki, Giza, Egypt.
出版信息
Adv Pharm Bull. 2015 Nov;5(4):569-81. doi: 10.15171/apb.2015.077. Epub 2015 Nov 30.
PURPOSE
The current work aimed to develop promising Fexofenadine hydrochloride (FXD) liquisolid tablets able to increase its oral bioavailability and shorten time to reach maximum plasma concentrations (Tmax).
METHODS
Eighteen liquisolid powders were developed based on 3 variables; (i) vehicle type [Propylene glycol (PG) or Cremophor(®) EL (CR)], (ii) carrier [Avicel(®) PH102] to coat [Aerosil(®) 200] ratio (15, 20, 25) and (iii) FXD concentration in vehicle (30, 35, 40 %, w/w). Pre-compression studies involved identification of physicochemical interactions and FXD crystallinity (FT-IR, DSC, XRD), topographic visualization (SEM) and estimation of flow properties (angle of repose, Carr's index, Hausner's ratio). CR-based liquisolid powders were compressed as liquisolid tablets (LST 9 - 18) and evaluated for weight-variation, drug-content, friability-percentage, disintegration-time and drug-release. The pharmacokinetics of LST-18 was evaluated in healthy volunteers relative to Allegra(®) tablets.
RESULTS
Pre-compression studies confirmed FXD dispersion in vehicles, conversion to amorphous form and formation of liquisolid powders. CR-based liquisolid powders showed acceptable-to-good flow properties suitable for compaction. CR-based LSTs had appropriate physicochemical properties and short disintegration times. Release profile of LST-18 showed a complete drug release within 5 min.
CONCLUSION
LST-18 succeeded in increasing oral FXD bioavailability by 62% and reducing Tmax to 2.16 h.
目的
当前研究旨在开发有前景的盐酸非索非那定（FXD）液固分散体片，以提高其口服生物利用度并缩短达最大血药浓度时间（Tmax）。
方法
基于3个变量开发了18种液固分散体粉末；（i）载体类型[丙二醇（PG）或聚氧乙烯蓖麻油（CR）]，（ii）载体[微晶纤维素（PH102）]与包衣材料[气相二氧化硅（200）]的比例（15、20、25），以及（iii）FXD在载体中的浓度（30%、35%、40%，w/w）。压片前研究包括确定物理化学相互作用和FXD结晶度（傅里叶变换红外光谱、差示扫描量热法、X射线衍射）、形貌可视化（扫描电子显微镜）以及流动性评估（休止角、卡尔指数、豪斯纳比）。以CR为基础的液固分散体粉末被压制成液固分散体片（LST 9 - 18），并对其进行重量差异、药物含量、脆碎度百分比、崩解时间和药物释放评估。在健康志愿者中评估LST - 18相对于阿乐格拉片的药代动力学。
结果
压片前研究证实FXD在载体中分散，转变为无定形形式并形成液固分散体粉末。以CR为基础的液固分散体粉末显示出适合压片的可接受至良好的流动性。以CR为基础的LST具有合适的物理化学性质和较短的崩解时间。LST - 18的释放曲线显示在5分钟内药物完全释放。
结论
LST - 18成功将口服FXD生物利用度提高了62%，并将Tmax缩短至2.16小时。
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