Rosuvastatin calcium nanoparticles: Improving bioavailability by formulation and stabilization codesign
Rosuvastatin calcium nanoparticles: Improving bioavailability by formulation and stabilization codesign
复制标题
DOI：
10.1371/journal.pone.0200218
复制
发表时间：
2018-07-09
期刊：
影响因子：
3.7
通讯作者：
Alanazi, Fars
中科院分区：
文献类型：
--
作者：
Alshora, Doaa H.;Ibrahim, Mohamed A.;Alanazi, Fars
目的瑞舒伐他汀钙（ROSCa）是一种难溶性药物，生物利用度不超过20%。减小粒径可提高其溶解度、溶出速率和生物利用度。因此，本研究的目的是通过行星式球磨机的湿磨技术制备ROSCa纳米颗粒。纳米颗粒的配方和稳定之间的协同设计进行了研究，以实现高的溶解度以及biobaic.MethodologyROSCa纳米混悬剂通过湿磨技术，使用行星式球磨机，通过应用研磨球的大小为0.1毫米，在800转/分的速度为3个周期，每个周期由10分钟组成。使用HPMC、PVP k-30、pluronic F-127、Tween 80和PEG 6000作为稳定剂。然后将纳米混悬液冷冻干燥，干燥的纳米颗粒进行了评价，粒径，zeta电位，体外溶出试验，XRPD和在vivo study.ResultsROSCa纳米粒稳定与10%PVP（P3）具有良好的稳定性与最小的粒径，这反过来又提高了溶出速率。与粒径为618 μ π ι的未处理药物相比，先导配方的粒径为461.8 +/-16.68 nm，ζ电位为-31.8 +/-7.22 mV。1小时后ROSCa的溶出百分比显著增加，主导纳米颗粒配方和未处理的ROSCa分别达到72%和58.25%（P < 0.05）。ROSCa从领先的纳米颗粒配方的体内研究表明，在Cmax 2小时后（82.35 ng/ml）的显着增强相比，9.2 ng/ml的未经处理的drug.ConclusionWet研磨技术是一种成功的方法来制备ROSCa纳米颗粒。从所用的不同稳定剂来看，PVP（10%）能够产生具有小粒径的稳定纳米粒，这显著提高了ROSCa的溶出速率和药代动力学参数。
PurposeRosuvastatin calcium (ROSCa) is a poorly soluble drug with bioavailability not exceeding 20%. Decreasing the particle size may enhance its solubility, dissolution rate and bioavailability. Therefore, the aim of the current study is to prepare ROSCa nanoparticles by wet milling technique using planetary ball mill. The codesign between formulation and stabilization of nanoparticles was studied to achieve both high dissolution as well as bioavailability.MethodologyROSCa nanosuspensions was prepared by wet milling technique using planetary ball mill, by applying milling ball size of 0.1 mm at speed of 800 rpm for 3 cycles each cycle composed of 10 minutes. HPMC, PVP k-30, pluronic F-127, Tween 80 and PEG 6000 were used as stabilizers. The nanosuspensions were then freeze-dried, and the dried nanoparticles were evaluated for particle size, zeta potential, in-vitro dissolution test, XRPD and in-vivo study.ResultsROSCa nanoparticles stabilized with 10% PVP (P3) had a good stability with smallest particle size, which in turn enhanced the dissolution rate. The particle size of the leading formula was 461.8 +/- 16.68 nm with zeta potential of -31.8 +/- 7.22 mV compared to untreated drug that has a particle size of 618pm. The percent of ROSCa dissolved after 1 hour enhanced significantly which reached 72% and 58.25% for leading nanoparticle formula and untreated ROSCa, respectively (P < 0.05). The in-vivo study of ROSCa from the leading nanoparticle formula showed a significant enhancement in the C max after 2 h (82.35 ng/ml) compared to 9.2 ng/ml for untreated drug.ConclusionWet milling technique is a successful method to prepare ROSCa nanoparticles. From different stabilizer used, PVP (10%) was able to produce stable nanoparticle with small particle size which significantly enhance the dissolution rate and pharmacokinetics parameters of ROSCa.