Zainuddin Rana, Zaheer Zahid, Sangshetti Jaiprakash N, Momin Mufassir
a Depatment of Quality Assurance, Y.B. Chavan College of Pharmacy , Dr. Rafiq Zakaria Campus , Aurangabad , India.
Drug Dev Ind Pharm. 2017 Dec;43(12):2076-2084. doi: 10.1080/03639045.2017.1371732. Epub 2017 Sep 13.
To synthesize β cyclodextrin nanosponges using a novel and efficient microwave mediated method for enhancing bioavailability of Rilpivirine HCl (RLP).
Belonging to BCS class II RLP has pH dependent solubility and poor oral bioavailability. However, a fatty meal enhances its absorption hence the therapy indicates that the dosage form be consumed with a meal. But then it becomes tedious and inconvenient to continue the therapy for years with having to face the associated gastric side effects such as nausea.
Microwave synthesizer was used to mediate the poly-condensation reaction between β-cyclodextrin and cross-linker diphenylcarbonate. Critical parameters selected were polymer to cross-linker ratio, Watt power, reaction time and solvent volume. Characterization studies were performed using FTIR, DSC, SEM, H-NMR and PXRD. Molecular modeling was applied to confirm the possibility of drug entrapment. In vitro drug dissolution followed by oral bioavailability studies was performed in Sprawley rats. Samples were analyzed using HPLC.
Microwave synthesis yields para-crystalline, porous nanosponges (∼205 nm). Drug entrapment led to enhancement of solubility and a two-fold increase in drug dissolution (P < 0.001) following Higuchi release model. Enhanced oral bioavailability was observed in fasted Sprawley rats where C and AUC increases significantly (C of NS∼ 586 ± 5.91 ng/mL; plain RLP ∼310 ± 5. 74 ng/mL).
The approach offers a comfortable dosing zone for AIDs patients, negating the requirement of consuming the formulation in a fed state due to enhancement in drugs' oral bioavailability.
采用一种新型高效的微波介导方法合成β-环糊精纳米海绵，以提高盐酸利匹韦林（RLP）的生物利用度。
RLP属于BCS II类药物，具有pH依赖性溶解性，口服生物利用度差。然而，高脂餐可增强其吸收，因此该疗法表明剂型需与食物一起服用。但多年持续治疗时，由于会出现恶心等相关胃部副作用，这变得繁琐且不方便。
使用微波合成仪介导β-环糊精与交联剂碳酸二苯酯之间的缩聚反应。选择的关键参数有聚合物与交联剂的比例、瓦特功率、反应时间和溶剂量。使用傅里叶变换红外光谱（FTIR）、差示扫描量热法（DSC）、扫描电子显微镜（SEM）、氢核磁共振（H-NMR）和粉末X射线衍射（PXRD）进行表征研究。应用分子模型来确认药物包封的可能性。在Sprawley大鼠中进行体外药物溶出及随后的口服生物利用度研究。使用高效液相色谱法（HPLC）分析样品。
微波合成产生准晶态、多孔的纳米海绵（约205纳米）。药物包封导致溶解度提高，按照 Higuchi 释放模型，药物溶出增加了两倍（P < 0.001）。在禁食的Sprawley大鼠中观察到口服生物利用度提高，其中血药浓度（C）和药时曲线下面积（AUC）显著增加（纳米海绵组的C约为586 ± 5.91纳克/毫升；普通RLP组约为310 ± 5.74纳克/毫升）。
该方法为艾滋病患者提供了一个舒适的给药区间，由于药物口服生物利用度提高，无需在进食状态下服用制剂。
