Al-Ghananeem Abeer M, Sandefer Erik P, Doll Walter J, Page Richard C, Chang Yunik, Digenis George A
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 927 Rose Street, Lexington, KY 40536, USA.
Int J Pharm. 2008 Jun 5;357(1-2):70-6. doi: 10.1016/j.ijpharm.2008.01.040. Epub 2008 Feb 1.
The present work was carried out to study the deposition patterns and clearance of technetium-99m (99mTc) DTPA labeled cromolyn sodium (CS) solutions when administered from two different CS nasal products using gamma scintigraphy. Five healthy volunteers received a single dose with complete crossover design involving treatment A (test formulation) and treatment B (reference formulation). The deposition patterns as well as the changes in distribution of the radiolabeled CS solutions due to the mucociliary transport were monitored by gamma scintigraphy. Primary deposition of the aforementioned nasal solutions occurred in the anterior portion of the nose. After migration into the posterior nasal cavity, the solutions were rapidly cleared by ciliary action into the nasopharynx where it was swallowed. The test product of cromolyn sodium was shown to be equivalent to the reference product with regard to nasal deposition and clearance. The results from this study indicate that external gamma scintigraphy can be used to demonstrate the equivalence of nasal sprays that are intended for local therapeutic action where the drug is not systemically absorbed into the blood circulation. Furthermore, a non-invasive imaging method such as rhinoscintigraphy may prove to be a useful technique to be utilized during the regulatory approval process for local-acting nasal products, and may facilitate the early introduction of these products to the market.
本研究旨在通过γ闪烁显像技术，研究从两种不同的色甘酸钠（CS）鼻腔制剂给药时，99m锝（99mTc）标记的二乙三胺五乙酸（DTPA）色甘酸钠溶液的沉积模式和清除情况。五名健康志愿者采用完全交叉设计接受单剂量治疗，包括治疗A（试验制剂）和治疗B（参比制剂）。通过γ闪烁显像监测放射性标记的CS溶液的沉积模式以及由于黏液纤毛运输导致的分布变化。上述鼻腔溶液的初始沉积发生在鼻前部。迁移至后鼻腔后，溶液通过纤毛作用迅速清除至鼻咽部并被吞咽。色甘酸钠试验产品在鼻腔沉积和清除方面显示与参比产品等效。本研究结果表明，外部γ闪烁显像可用于证明旨在产生局部治疗作用且药物不会全身吸收进入血液循环的鼻腔喷雾剂的等效性。此外，诸如鼻闪烁显像等非侵入性成像方法可能被证明是一种在局部作用鼻腔产品的监管审批过程中有用的技术，并且可能有助于这些产品早日上市。
