Omar Samia M, Ibrahim Fares, Ismail Aliaa
Department of Pharmaceutics, Faculty of Pharmacy, Helwan University, Egypt.
Department of Pharmaceutics, Faculty of Pharmacy, Ahram Canadian University, Egypt.
Saudi Pharm J. 2020 Mar;28(3):349-361. doi: 10.1016/j.jsps.2020.01.016. Epub 2020 Feb 3.
The aim of this study was the development of griseofulvin (GRI) loaded β-cyclodextrin (β-CD) based nanosponges for bitter taste masking, improving dissolution rate and oral bioavailability. Plain NS (NS1 NS2 and NS3) were fabricated by reacting β-CD with the cross-linker diphenyl carbonate at different molar ratios (1:2, 1:4 and 1:6, respectively) using ultrasonication method. The NS2 provided both highest %yield and GRI solubilization enhancement. Thus, the drug was loaded in NS2 at different NS2: drug weight ratios in presence or absence of 0.25%w/w polyvinylpyrolidone (PVP k30). The GRI loaded NS (F1) that provided highest drug loading capacity and entrapment efficiency (47.20 0.38%, 84.91 ± 0.30%, respectively) was morphologically examined using scanning electron microscopy (SEM). Also, Particle size, zeta potential, differential scanning calorimetry (DSC), Fourier transform infra-red (FT-IR), nuclear magnetic resonance (NMR) spectroscopy, release, taste masking potential were evaluated. Moreover, Pharmacokinetic studies were performed on rats. The F1 showed particle size 665.9 ± 13.8 nm and zeta potential -21.5 ± 0.7 mV. The DSC and FT-IR analysis confirmed the complexation of GRI with NS2. Nanosponges (F1) provided 3.19, folds increase in dissolution efficiency %, 2.13 and 3.78 folds increase in C and AUC compared to plain GRI. Taste masking evaluation confirmed the potential of GRI nanosponges (F1) in masking the bitter taste of GRI completely. The study confirmed that complexation of GRI with NS would be a viable approach for masking the bitter taste of GRI and improving oral bioavailability, that Cmax, Tmax and AUC 0-48 were significantly higher for the developed formulation (F1).
本研究的目的是开发负载灰黄霉素（GRI）的基于β-环糊精（β-CD）的纳米海绵，用于掩盖苦味、提高溶解速率和口服生物利用度。通过超声法使β-CD与交联剂碳酸二苯酯以不同摩尔比（分别为1:2、1:4和1:6）反应制备普通纳米海绵（NS1、NS2和NS3）。NS2的产率百分比和GRI增溶效果均最高。因此，在存在或不存在0.25%w/w聚乙烯吡咯烷酮（PVP k30）的情况下，将药物以不同的NS2:药物重量比负载于NS2中。使用扫描电子显微镜（SEM）对具有最高载药量和包封率（分别为47.20±0.38%、84.91±0.30%）的负载GRI的纳米海绵（F1）进行形态学检查。此外，还评估了粒径、zeta电位、差示扫描量热法（DSC）、傅里叶变换红外光谱（FT-IR）、核磁共振（NMR）光谱、释放度、苦味掩盖潜力。此外，还对大鼠进行了药代动力学研究。F1的粒径为665.9±13.8 nm，zeta电位为-21.5±0.7 mV。DSC和FT-IR分析证实了GRI与NS2的络合。与普通GRI相比，纳米海绵（F1）的溶出效率百分比提高了3.19倍，Cmax和AUC分别提高了2.13倍和3.78倍。苦味掩盖评估证实了GRI纳米海绵（F1）完全掩盖GRI苦味的潜力。该研究证实，GRI与NS的络合将是掩盖GRI苦味和提高口服生物利用度的可行方法，所开发的制剂（F1）的Cmax、Tmax和AUC 0-48显著更高。
