a Department of Pharmaceutics , National Organization of Drug Control and Research (NODCAR) , Giza , Egypt.
b Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy , MTI University , Cairo , Egypt.
Drug Deliv. 2019 Dec;26(1):689-699. doi: 10.1080/10717544.2019.1618419.
Enhancement of zolmitriptan bioavailability through development of micronized zolmitriptan pressurized metered dose inhaler (MDI) as an alternative to its traditional drug delivery systems. A reversed phase HPLC method for zolmitriptan determination was developed and evaluated. Micronized zolmitriptan MDI formulations were prepared using two different propellants. The prepared formulations were evaluated for mean shot weight, drug content, and leakage rate in addition to in-vitro deposition using next generation impactor where mass median aerodynamic diameter (MMAD), geometric standard deviation (GSD), fine particle dose, fine particle fraction (FPF), emitted dose (ED), and dispersibility were determined. The selected formulation was evaluated for in-vivo bronchial absorption in rats. The physicochemical characters of the prepared formulations were found to be dependent mainly on the vapor pressure of the used propellant. MDI formulation prepared with HFA 134a propellant was found to have the lowest MMAD (3.47 ± 0.65) with GSD of 2.3 ± 0.4. It also had the highest FPF (41.9), ED (89.26 ± 2.35) with dispersibility of 46.9%. This formulation, when applied to rats, resulted in faster (27 ± 5 min) with higher (1236 ± 116 ng/mL) and AUC (3375 ± 482 ng/mL·h) over the oral tablet. Its relative bioavailability was 72.7% which was 1.25 times higher than the oral tablet relative bioavailability. Zolmitriptan MDI formulation was developed using micronized zolmitriptan powder without further modification or particle engineering. The developed formulation using HFA 134a propellant could be favorable alternative, with enhanced bioavailability, to zolmitriptan oral tablet for acute migraine treatment.
通过开发米氮平微粉化的压力定量吸入器（MDI）作为其传统药物输送系统的替代品来提高佐米曲坦的生物利用度。建立并评价了一种反相高效液相色谱法来测定佐米曲坦的含量。使用两种不同的推进剂制备了米氮平微粉化 MDI 制剂。对所制备的制剂进行了平均喷雾重量、药物含量和泄漏率的评价，以及使用下一代撞击器进行了体外沉积评价，其中测定了质量中值空气动力学直径（MMAD）、几何标准偏差（GSD）、细颗粒剂量、细颗粒分数（FPF）、发射剂量（ED）和分散性。对选定的制剂进行了在体支气管吸收的大鼠试验。所制备的制剂的理化性质主要取决于所使用推进剂的蒸气压。使用 HFA 134a 推进剂制备的 MDI 制剂具有最低的 MMAD（3.47±0.65），GSD 为 2.3±0.4。它还具有最高的 FPF（41.9）、ED（89.26±2.35）和分散度（46.9%）。当将该制剂应用于大鼠时，其达到峰浓度的时间更快（27±5min），其 AUC（3375±482ng/mL·h）更高（1236±116ng/mL）。其相对生物利用度为 72.7%，是口服片剂的相对生物利用度的 1.25 倍。使用米氮平微粉化粉末开发了佐米曲坦 MDI 制剂，无需进一步的修饰或颗粒工程。使用 HFA 134a 推进剂开发的制剂可以作为佐米曲坦口服片剂的一种有利替代品，用于急性偏头痛的治疗，具有增强的生物利用度。
