Amorphous Solid Solutions in Glassy Hydrogels for Enhancing the Delivery of Poorly Soluble Drugs
玻璃状水凝胶中的无定形固溶体增强难溶性药物的递送
基本信息
- 批准号:RGPIN-2019-05459
- 负责人:
- 金额:$ 2.04万
- 依托单位:
- 依托单位国家:加拿大
- 项目类别:Discovery Grants Program - Individual
- 财政年份:2022
- 资助国家:加拿大
- 起止时间:2022-01-01 至 2023-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
One major challenge in oral drug delivery has been the low bioavailability of many crystalline compounds exhibiting poor solubility characteristics. Traditional methods for solubility enhancement involving solubilizing agents (e.g. co-solvents & surfactants) and particle size reduction have not always been successful. On the other hand, the creation of solid solutions (molecular dispersions) in soluble polymers has shown potential to be effective in enhancing the dissolution and oral bioavailability due to the higher solubility of the amorphous drug (supersaturation). However, the mechanisms of drug dissolution and release from amorphous solid solutions and their effect on the overall time evolution of supersaturation during dissolution are not well understood and have not been fully explored. In addition, physical instability of these systems during storage such as crystallization on aging has limited their success in commercial applications. Furthermore, no criterion exists in determining the threshold drug loading level above which crystallization may occur in these soluble polymers. Despite the ongoing interest in hydrogels as biomaterials and carriers for controlled drug release, the novel application of cross-linked glassy hydrogels for stabilizing the loaded drug in an amorphous state has not been fully investigated. Cross-linked hydrogels are more advantageous than soluble polymers in this regard since the three-dimensional network in the glassy state is more effective in preventing the crystallization of loaded amorphous drug. Experimental evidence suggests that solid solutions based on hydrogels can also avoid peaks and valleys in the kinetic solubility profiles normally associated with solid solutions based on soluble polymers, thereby achieving a more sustained drug supersaturation than conventional systems based on soluble polymers. We therefore propose to conduct an in-depth investigation of this hydrogel-based system and identify the optimal range of design parameters that can effectively inhibit the crystallization of loaded drug and maximize the supersaturation maintenance to enhance the delivery of poorly soluble drugs.
口服给药的一个主要挑战是许多晶体化合物的生物利用度低,这些化合物表现出较差的溶解特性。使用增溶剂(如共溶剂和表面活性剂)和减小颗粒尺寸的传统增溶方法并不总是成功的。另一方面,由于无定形药物(过饱和)的较高溶解度,在可溶聚合物中形成固体溶液(分子分散体)在提高药物的溶出度和口服生物利用度方面具有潜在的潜力。然而,药物在非晶态固溶体中的溶解和释放机制以及它们对药物在溶出过程中过饱和时间演化的影响还不是很清楚,也没有得到充分的研究。此外,这些体系在储存过程中的物理不稳定性,如老化结晶,限制了它们在商业应用中的成功。此外,在确定这些可溶聚合物中可能发生结晶的阈值载药量水平方面没有标准。尽管人们对水凝胶作为生物材料和药物控制释放载体的兴趣与日俱增,但用于稳定无定形药物的交联玻璃水凝胶的新应用还没有得到充分的研究。在这方面,交联水凝胶比可溶性聚合物更有优势,因为玻璃态的三维网络在防止负载的无定形药物结晶方面更有效。实验证据表明,基于水凝胶的固体溶液还可以避开通常与基于可溶聚合物的固体溶液相关的动力学溶解度分布中的峰和谷,从而实现比基于可溶聚合物的传统体系更持久的药物过饱和。因此,我们建议对这种基于水凝胶的系统进行深入的研究,并确定能够有效抑制所加载药物的结晶并最大限度地保持过饱和度以增强难溶药物的输送的最佳设计参数范围。
项目成果
期刊论文数量(0)
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Lee, Ping其他文献
Lee, Ping的其他文献
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{{ truncateString('Lee, Ping', 18)}}的其他基金
Amorphous Solid Solutions in Glassy Hydrogels for Enhancing the Delivery of Poorly Soluble Drugs
玻璃状水凝胶中的无定形固溶体增强难溶性药物的递送
- 批准号:
RGPIN-2019-05459 - 财政年份:2021
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Amorphous Solid Solutions in Glassy Hydrogels for Enhancing the Delivery of Poorly Soluble Drugs
玻璃状水凝胶中的无定形固溶体增强难溶性药物的递送
- 批准号:
RGPIN-2019-05459 - 财政年份:2020
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Amorphous Solid Solutions in Glassy Hydrogels for Enhancing the Delivery of Poorly Soluble Drugs
玻璃状水凝胶中的无定形固溶体增强难溶性药物的递送
- 批准号:
RGPIN-2019-05459 - 财政年份:2019
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Evolution of Supersaturation Generated from Amorphous Solid Solutions of Poorly Soluble Drugs in Glassy Hydrogels
玻璃状水凝胶中难溶药物的无定形固溶体产生的过饱和度的演变
- 批准号:
RGPIN-2014-06478 - 财政年份:2018
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Evolution of Supersaturation Generated from Amorphous Solid Solutions of Poorly Soluble Drugs in Glassy Hydrogels
玻璃状水凝胶中难溶药物的无定形固溶体产生的过饱和度的演变
- 批准号:
RGPIN-2014-06478 - 财政年份:2017
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Evolution of Supersaturation Generated from Amorphous Solid Solutions of Poorly Soluble Drugs in Glassy Hydrogels
玻璃状水凝胶中难溶药物的无定形固溶体产生的过饱和度的演变
- 批准号:
RGPIN-2014-06478 - 财政年份:2016
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Evolution of Supersaturation Generated from Amorphous Solid Solutions of Poorly Soluble Drugs in Glassy Hydrogels
玻璃状水凝胶中难溶药物的无定形固溶体产生的过饱和度的演变
- 批准号:
RGPIN-2014-06478 - 财政年份:2015
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Evolution of Supersaturation Generated from Amorphous Solid Solutions of Poorly Soluble Drugs in Glassy Hydrogels
玻璃状水凝胶中难溶药物的无定形固溶体产生的过饱和度的演变
- 批准号:
RGPIN-2014-06478 - 财政年份:2014
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Swelling-controlled solute diffusion in glassy polymers
玻璃态聚合物中溶胀控制的溶质扩散
- 批准号:
326813-2007 - 财政年份:2010
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Swelling-controlled solute diffusion in glassy polymers
玻璃态聚合物中溶胀控制的溶质扩散
- 批准号:
326813-2007 - 财政年份:2009
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
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- 批准号:
RGPIN-2019-05459 - 财政年份:2021
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
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