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首页> 外文学位 >The evaluation of larch arabinogalactan as a new carrier in the formulation of solid dispersions of poorly water- soluble drugs.
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The evaluation of larch arabinogalactan as a new carrier in the formulation of solid dispersions of poorly water- soluble drugs.

机译：对落叶松阿拉伯半乳聚糖作为难溶性药物固体分散体制剂中新载体的评价。

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摘要

Advanced drug discovery techniques have produced more lipophilic compounds. Formation of an amorphous solid dispersion of such poorly water-soluble drugs improves their solubility and dissolution. This results in greater in vivo bioavailability. Thus, it is one of the recent trends in the development of oral dosage forms. In solid dispersions, the carrier is crucial for ensuring the functionality and stability of these systems. Larch arabinogalactan FiberAid grade (AGF) is generally recognized as safe (GRAS) designated, amorphous polymer. The objective of this dissertation project was to perform a comprehensive evaluation of AGF as a carrier for amorphous solid dispersions.;First, a detailed characterization of the AGF polymer was performed. A special focus on its use as a solid dispersion carrier was emphasized. The glass transition temperature and the degradation temperature of the AGF polymer were ∼82 °C and ∼185 °C, respectively. The AGF polymer had good hygroscopicity. Ibuprofen-AGF solid dispersions were evaluated for dissolution enhancement. Ibuprofen-Hydroxypropyl methylcellulose grade K3 (HPMCK3) solid dispersions were investigated simultaneously as a control polymer dispersion. The ibuprofen-AGF solid dispersions were amorphous at nearly 20% ibuprofen load. The dissolution of the ibuprofen from AGF solid dispersions was significantly greater than that of the neat ibuprofen. The formation of the amorphous state of ibuprofen and solution-state ibuprofen-AGF interactions were the mechanisms of the ibuprofen dissolution enhancement. At a 10% ibuprofen load, the dissolution of the AGF solid dispersion was found greater than that of the dissolution of the HPMCK3 solid dispersion.;Secondly, the itraconazole-AGF solid dispersions and the ketoprofen-AGF solid dispersions were characterized and compared them with the ibuprofen-AGF solid dispersions. The comparisons were established for the miscibility and dissolution enhancement. The order of increase in dissolution was ketoprofen-AGF solid dispersions > itraconazole-AGF solid dispersions> ibuprofen-AGF solid dispersions. The same order was observed for the solid-state miscibility of these drug-AGF solid dispersions.;Additionally, the solid dispersions of 9 drugs with the AGF polymer were investigated to elucidate the detailed mechanism of drug crystallization inhibition by the AGF polymer. The inherent tendency of the AGF polymer to inhibit the drug crystallization, drug-AGF solid-state hydrogen bonding and the anti-plasticizing effect of AGF were the mechanisms underlying the crystallization inhibition by the AGF polymer.;Last, a storage stability of ibuprofen-AGF amorphous solid dispersions after storage under accelerated conditions (for 3 months) and ambient conditions (for 6 months) was investigated. The amorphous ibuprofen from AGF solid dispersions was physically and chemically stable under stability conditions.;In summary, the AGF polymer was evaluated as a novel carrier for formation of an amorphous solid dispersions. The studies established that the AGF polymer was comparable to HPMCK3 polymer. The AGF polymer could be more advantageous than the HPMC polymer for the preparation of solid dispersion when faster dissolution is desired at lower drug load.
机译：先进的药物发现技术已经产生了更多的亲脂性化合物。这种水溶性差的药物的无定形固体分散体的形成改善了它们的溶解性和溶解性。这导致更高的体内生物利用度。因此，这是口服剂型开发的最新趋势之一。在固体分散体中，载体对于确保这些系统的功能和稳定性至关重要。落叶松阿拉伯半乳聚糖FiberAid级（AGF）通常被认为是安全（GRAS）指定的无定形聚合物。本研究项目的目的是对作为无定形固体分散体载体的AGF进行综合评估。首先，对AGF聚合物进行详细的表征。特别强调了将其用作固体分散载体。 AGF聚合物的玻璃化转变温度和降解温度分别为〜82℃和〜185℃。该AGF聚合物具有良好的吸湿性。评价布洛芬-AGF固体分散体的溶出度增强。同时研究了布洛芬-羟丙基甲基纤维素K3级（HPMCK3）固体分散体作为对照聚合物分散体。布洛芬-AGF固体分散体在布洛芬负荷接近20％时为无定形。布洛芬从AGF固体分散体中的溶解明显大于纯布洛芬。布洛芬的无定形状态和溶液状态的布洛芬-AGF相互作用是布洛芬溶解增强的机制。在布洛芬10％的负载下，发现AGF固体分散体的溶解度大于HPMCK3固体分散体的溶解度;其次，对伊曲康唑-AGF固体分散体和酮洛芬-AGF固体分散体进行了表征并与布洛芬-AGF固体分散体。建立了混溶性和溶出度增强的比较。溶解度增加的顺序为酮洛芬-AGF固体分散体>伊曲康唑-AGF固体分散体>布洛芬-AGF固体分散体。对于这些药物-AGF固体分散体的固态混溶性，观察到的顺序相同。此外，还研究了9种药物与AGF聚合物的固体分散体，以阐明AGF聚合物抑制药物结晶的详细机理。 AGF聚合物抑制药物结晶，药物-AGF固态氢键和AGF的抗塑化作用的固有趋势是AGF聚合物抑制结晶的机制。最后，布洛芬-的储存稳定性研究了在加速条件（3个月）和环境条件（6个月）下储存后的AGF无定形固体分散体。在稳定条件下，来自AGF固体分散体的无定形布洛芬在物理和化学上是稳定的。总之，AGF聚合物被评价为用于形成无定形固体分散体的新型载体。研究确定，AGF聚合物可与HPMCK3聚合物媲美。当需要在较低的药物负荷下更快地溶解时，AGF聚合物比HPMC聚合物更有利于制备固体分散体。

著录项

  • 作者

    Thakare, Kalpana.;

  • 作者单位

    Temple University.;

  • 授予单位 Temple University.;
  • 学科 Health Sciences Pharmacy.
  • 学位 Ph.D.
  • 年度 2013
  • 页码 387 p.
  • 总页数 387
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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