Stange Ulrike, Führling Christian, Gieseler Henning
Freeze Drying Focus Group (FDFG), Division of Pharmaceutics, University of Erlangen, Erlangen, 91058, Germany.
J Pharm Sci. 2014 Apr;103(4):1233-45. doi: 10.1002/jps.23896. Epub 2014 Feb 15.
The purpose of this study was to develop and manufacture novel freeze-dried orally disintegrating tablets (ODTs) for migraine therapy containing taste-masked naproxen sodium and naratriptan hydrochloride. The formulation was optimized based on freeze-drying of sucrose solutions with different binders (hydroxyethylstarch, sodium alginate, methylcellulose, and gelatin) and varying amounts of Eudragit® E-coated naproxen sodium granules. Excellent product performance of the ODTs in terms of hardness and disintegration time (<10 s) independent of the mass of particles embedded was found for the solution consisting of sucrose and hydroxyethylstarch. Poloxamer 188, menthol flavor, naratriptan hydrochloride, and taste-masked naproxen sodium granules corresponding to 200 mg of naproxen were then added, and the final batches of ODTs for migraine therapy were produced. The ODTs were fully characterized, and subsequently stored for 1 month at room temperature and at 40°C. The amount of free naproxen sodium after freeze-drying and storage was below the threshold bitterness value, and the coating remained intact. Additionally, the particle size distribution of taste-masked granules was preserved, and more than 90 % naproxen sodium was released after 30 min. Naratriptan hydrochloride was dissolved immediately after disintegration, hence facilitating buccal absorption of the active pharmaceutical ingredient.
本研究的目的是开发并制造用于偏头痛治疗的新型冻干口腔崩解片（ODT），该片剂含有掩味的萘普生钠和盐酸那拉曲普坦。基于用不同粘合剂（羟乙基淀粉、海藻酸钠、甲基纤维素和明胶）以及不同量的Eudragit® E包衣萘普生钠颗粒对蔗糖溶液进行冻干，对配方进行了优化。对于由蔗糖和羟乙基淀粉组成的溶液，发现ODT在硬度和崩解时间（<10秒）方面具有优异的产品性能，且与嵌入颗粒的质量无关。然后加入泊洛沙姆188、薄荷醇香料、盐酸那拉曲普坦以及相当于200 mg萘普生的掩味萘普生钠颗粒，生产出用于偏头痛治疗的最终批次的ODT。对ODT进行了全面表征，随后在室温下和40°C下储存1个月。冻干和储存后游离萘普生钠的量低于阈值苦味值，且包衣保持完整。此外，掩味颗粒的粒度分布得以保留，30分钟后超过90%的萘普生钠被释放。盐酸那拉曲普坦在崩解后立即溶解，从而促进活性药物成分的颊部吸收。
