Correlation of surface properties with dissolution behavior of amorphous solid dispersion of Riluzole and its pharmacodynamic evaluation.

IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL
Kanchan Bharti, Abhishek Jha, Manish Kumar, Manjit, Amol Parasram Satpute, Akhilesh, Vinod Tiwari, Brahmeshwar Mishra
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Abstract

Formulation of amorphous solid dispersion (ASD) of any poorly water-soluble drug is among the most promising techniques to increase the dissolution profile of drug and hence its bioavailability. Various literatures give evidences of the role of drug-polymer interactions in the ASD systems, very little information is available about the surface properties of the drug molecule and their ASDs which contributes to a higher dissolution profile. Current work focuses on exploring the surface behavior of a poorly water-soluble drug Riluzole (RLZ) and its ASDs prepared with two highly hydrophilic polymers, polyacrylic acid (PAA), and polyvinylpyrrolidone vinyl acetate (PVP VA). Initial characterization using X-ray diffraction (XRD) revealed about the weight fraction of drug required to prepare a single-phase homogenous system with both the polymers. The saturation solubility and the dissolution studies showed an increase in RLZ solubility as well as the dissolution profile due to the presence of polymers. The role of polymers in changing the surface properties in terms of wettability and polarity were explored using contact angle method and X-ray photon spectroscopy (XPS). Additionally, the neuroprotective efficacy and dose dependent hepatotoxicity were also evaluated in male wistar rats. These studies confirmed the increase in the surface polarity and hence the enhanced ability of ASD formulations to interact with water. The in vivo studies indicated that at the current recommended dose the efficacy as well as toxicity is increased for the ASD formulation. Hence, this formulation can be given at a lower dose to achieve same therapeutic effect with lower toxicity.

利鲁唑无定形固体分散体表面特性与溶解行为的相关性及其药效学评价
配制任何水溶性差的药物的无定形固体分散体(ASD)是最有前途的技术之一,可提高药物的溶解度,从而提高其生物利用率。各种文献都证明了药物-聚合物相互作用在 ASD 系统中的作用,但有关药物分子及其 ASD 的表面特性(这有助于提高溶出度)的信息却很少。目前的工作重点是探索水溶性较差的药物利鲁唑(RLZ)及其用两种高亲水性聚合物(聚丙烯酸(PAA)和聚乙烯吡咯烷酮醋酸乙烯酯(PVP VA))制备的 ASD 的表面行为。利用 X 射线衍射 (XRD) 进行的初步表征显示了用这两种聚合物制备单相均匀体系所需的药物重量分数。饱和溶解度和溶解研究表明,由于聚合物的存在,RLZ 的溶解度和溶解曲线都有所提高。使用接触角法和 X 射线光子光谱法(XPS)探讨了聚合物在改变润湿性和极性等表面特性方面的作用。此外,还对雄性 Wistar 大鼠的神经保护功效和剂量依赖性肝毒性进行了评估。这些研究证实,ASD 制剂的表面极性增加,因此与水相互作用的能力增强。体内研究表明,在目前的推荐剂量下,ASD 制剂的药效和毒性都有所提高。因此,这种制剂可以用较低的剂量达到相同的治疗效果,但毒性较低。
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来源期刊
CiteScore
7.30
自引率
13.20%
发文量
367
审稿时长
33 days
期刊介绍: The Journal of Pharmaceutical Sciences will publish original research papers, original research notes, invited topical reviews (including Minireviews), and editorial commentary and news. The area of focus shall be concepts in basic pharmaceutical science and such topics as chemical processing of pharmaceuticals, including crystallization, lyophilization, chemical stability of drugs, pharmacokinetics, biopharmaceutics, pharmacodynamics, pro-drug developments, metabolic disposition of bioactive agents, dosage form design, protein-peptide chemistry and biotechnology specifically as these relate to pharmaceutical technology, and targeted drug delivery.
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