Gulsun T, Ozturk N, Kaynak M S, Vural I, Sahin S
Pharmazie. 2017 Jul 3;72(7):389-394. doi: 10.1691/ph.2017.6149.
The purpose of this research was to develop and prepare orally disintegrating tablets (ODTs) containing furosemide by direct compression method. Furosemide, microcrystalline cellulose (MCC), low-substituted hydroxypropylcellulose LH-11 (L-HPC), aspartame, sodium stearyl fumarate were used for ODT formulation. MCC and L-HPC were used in ratios of 1:9 (ODT1) and 1:4 (ODT2). The results of the quality control parameters obtained for bulk powders (angle of repose, compressibility index, Hausner ratio, bulk density and volume, apparent density and volume, swelling of superdisintegrants and powder moisture) were taken as an indication of good compressibility of tablets. Both ODT1 and ODT2 disintegrated within 15 s and fulfilled the required disintegration time given by the European Pharmacopoeia (3 min). The average weight variation was less than 5% for both tablets. The friability of the tablets was less than 1%. Wetting time of both tablets was in the range of 12-21.7 s. Water absorption ratio was 1.41±0.03 for ODT1 and 1.96±0.10 for ODT2. Dissolution studies revealed that more than 85% of furosemide was dissolved in 15 min from both ODTs. Based on cell culture studies, permeability of furosemide was low (Papp=1x10-5 cm/s) but increased when prepared in the ODT form (ODT1: Papp=2x10-5 cm/s; ODT2: Papp=3.6x10-5 cm/s). Collectively, all these results showed that ODT formulations of furosemide were developed successfully. To improve patient compliance, ODT approach can be suggested for development and manufacturing of furosemide ODTs.
本研究的目的是通过直接压片法研制并制备含呋塞米的口腔崩解片(ODT)。将呋塞米、微晶纤维素(MCC)、低取代羟丙基纤维素LH - 11(L - HPC)、阿斯巴甜、硬脂酰富马酸钠用于ODT制剂。MCC和L - HPC的使用比例分别为1:9(ODT1)和1:4(ODT2)。对原料药获得的质量控制参数(休止角、压缩性指数、豪斯纳比、堆密度和体积、表观密度和体积、超级崩解剂的溶胀和粉末水分)结果被视为片剂良好可压性的指标。ODT1和ODT2均在15秒内崩解,并符合欧洲药典规定的所需崩解时间(3分钟)。两种片剂的平均重量差异均小于5%。片剂的脆碎度小于1%。两种片剂的润湿时间在12 - 21.7秒范围内。ODT1的吸水率为1.41±0.03,ODT2为1.96±0.10。溶出度研究表明,两种ODT在15分钟内呋塞米的溶出量均超过85%。基于细胞培养研究,呋塞米的渗透率较低(Papp = 1×10 - 5 cm/s),但制成ODT形式时有所增加(ODT1:Papp = 2×10 - 5 cm/s;ODT2:Papp = 3.6×10 - 5 cm/s)。总体而言,所有这些结果表明呋塞米的ODT制剂研制成功。为提高患者依从性,可建议采用ODT方法来研发和生产呋塞米ODT。