表面吸附固体分散体提高难溶性消旋卡多曲生物利用度的研究

IF 0.7 Q4 PHARMACOLOGY & PHARMACY Journal of Reports in Pharmaceutical Sciences Pub Date : 2021-01-01 DOI:10.4103/jrptps.JRPTPS_129_19
Bhaskar Daravath, G. Kumari
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引用次数: 4

摘要

生物制药分类系统II类药物根据其溶解度显示不可预测的生物利用度。不幸的是,由于这种技术的流动性和稳定性差,很少有产品被制造出来。本研究的目的是利用表面固体分散(SSD;SD(表面吸附技术),提高消旋卡多曲(RT)在低pH条件下(即在胃中)的吸收,通过减少水和电解质分泌到肠道中来发挥止泻作用。材料和方法:采用不同比例的亲水性载体(聚乙二醇4000、聚乙二醇6000和Gelucire 50/13)和吸附剂(乳糖一水合物)制备固态硬盘和物理混合物(pm)。采用傅里叶变换红外光谱、差示扫描量热法、x射线衍射法和体外溶出度研究来表征固态硬盘和pmms。结果:相溶解度曲线呈AL型,表明药物的溶解度随载体浓度的增加而线性增加。表征研究表明,载体与药物无相互作用。固态表征表明结晶度的降低进一步支持了溶解度和溶解性的增加。优化后的制剂(SDG4) 15 min释药率为99.84±1.5%,而RT平药释药率为11.95±1.72%。体内生物利用度研究显示,与RT普通药物相比,SDG4的Cmax增加了65.38±1.34µg/mL(1.75倍),相对生物利用度增加了180.22倍(P < 0.05)。结论:表面吸附法制备SD可提高RT的溶解度、溶出度和生物利用度。
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Improvement of bioavailability of poorly soluble racecadotril by solid dispersion with surface adsorption method: A case study
Introduction: Biopharmaceutics classification system class II drugs show unpredictable bioavailability based on their solubility. Unfortunately, very few products were manufactured by this technique owing to their poor flowability and stability. The objective of the current investigation was used to improve the flowability by surface solid dispersion (SSD; SD with surface adsorption technology) and improve the absorption of racecadotril (RT) under low pH conditions (i.e., in stomach) to show anti-diarrheal effect by reducing water and electrolyte secretion into the intestine. Materials and Methods: SSDs and physical mixtures (PMs) were prepared using various ratios of hydrophilic carriers (polyethylene glycol 4000, polyethylene glycol 6000, and Gelucire 50/13) and an adsorbent (lactose monohydrate). Fourier-transform infrared spectroscopy, differential scanning calorimetry, X-ray diffractometry , and dissolution studies (in vitro) were conducted to characterize SSDs and PMs. Results: Phase solubility curves represent AL type, indicating that the solubility of drug linearly increased with an increase in the concentration of carrier. Characterization studies indicated that no interactions between carrier and drug. Solid-state characterization showed a reduction in crystallinity that further supports increment in solubility and dissolution. The optimized formulation (SDG4) showed 99.84 ± 1.5% drug release in 15 min compared to RT plain drug (11.95 ± 1.72%). In vivo bioavailability studies of SDG4 revealed a significant (P < 0.05) increase in Cmax 65.38 ± 1.34 µg/mL (1.75-fold) with increased relative bioavailability (180.22-fold) against the RT plain drug. Conclusion: Formulation of SD with surface adsorption method could enhance solubility, dissolution, and bioavailability of RT.
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来源期刊
Journal of Reports in Pharmaceutical Sciences
Journal of Reports in Pharmaceutical Sciences Pharmacology, Toxicology and Pharmaceutics-Pharmacology, Toxicology and Pharmaceutics (all)
CiteScore
1.40
自引率
0.00%
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0
期刊介绍: The Journal of Reports in Pharmaceutical Sciences(JRPS) is a biannually peer-reviewed multi-disciplinary pharmaceutical publication to serve as a means for scientific information exchange in the international pharmaceutical forum. It accepts novel findings that contribute to advancement of scientific knowledge in pharmaceutical fields that not published or under consideration for publication anywhere else for publication in JRPS as original research article. all aspects of pharmaceutical sciences consist of medicinal chemistry, molecular modeling, drug design, pharmaceutics, biopharmacy, pharmaceutical nanotechnology, pharmacognosy, natural products, pharmaceutical biotechnology, pharmacology, toxicology and clinical pharmacy.
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