Software toolkits for in silico screening of polymer excipients in drug formulations

用于药物配方中聚合物赋形剂计算机筛选的软件工具包

• 批准号: 2879915
• 金额: --
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2879915
• 关键词: Software; toolkits; silico; screening; polymer

Pharmaceutical formulation is a key step of the drug development process where the active pharmaceutical ingredient (API) is mixed with non-drug components (excipients) which degrade in the body, usually as a function of time or pH, releasing the API in the target tissue.Biocompatible polymers like cellulose derivatives or glycols are common excipients in tablet formulations. Polymer degradation, crystallinity and mechanical properties can be easily tuned by changing their molecular weight or by chemical functionalisation. These features in turn affect product shelf life, drug release time and effective API concentration in the gastrointestinal tract. Copolymers of PEG or PVA are particularly suitable to promote the uptake of poorly soluble drugs. However, their complex semicrystalline morphology varies with subtle changes incomposition and processing conditions, making their performance and API compatibility hard to predict.Selecting polymer excipients for drug formulations is a time-consuming, mostly trial-and-errorprocess. While in silico screening (cheminformatics, machine learning) is routinely employed in small molecule drug discovery, such tools are not readily applicable to polymers. Simulations of excipients are done using 'computational microscope' molecular dynamics (MD) techniques with off-the-shelf parameters, which cannot be tailored to specific excipients. This is due to several factors, namely the lack of automated parameterisation software - an issue Open Force Field, alarge industry backed consortium, is starting to tackle.Accurately describing polymer flexibility is key, as torsional degrees of freedom are directly related to aggregation and crystallinity. Overall, the lack of reliable workflows and tools for polymer screening of functional is an open challenge across the fields of biochemistry, formulation science, materials science.

药物配方是药物开发过程的关键步骤，其中活性药物成分 (API) 与非药物成分（赋形剂）混合，这些成分通常会随着时间或 pH 值的变化在体内降解，从而将 API 释放到目标组织中。纤维素衍生物或二醇等生物相容性聚合物是片剂配方中常见的赋形剂。聚合物的降解、结晶度和机械性能可以通过改变其分子量或化学官能化来轻松调节。这些特性反过来又影响产品的保质期、药物释放时间和胃肠道中的有效 API 浓度。 PEG或PVA的共聚物特别适合促进难溶性药物的吸收。然而，它们复杂的半结晶形态会随着成分和加工条件的细微变化而变化，使得它们的性能和 API 兼容性难以预测。为药物配方选择聚合物赋形剂是一个耗时的、主要是反复试验的过程。虽然计算机筛选（化学信息学、机器学习）通常用于小分子药物发现，但此类工具并不容易适用于聚合物。辅料的模拟是使用“计算显微镜”分子动力学 (MD) 技术和现成的参数来完成的，这些参数无法针对特定的辅料进行定制。这是由于几个因素造成的，即缺乏自动参数化软件 - Open Force Field（一个大型行业支持的联盟）正在开始解决这个问题。准确描述聚合物的柔韧性是关键，因为扭转自由度与聚集和结晶度直接相关。总体而言，缺乏可靠的功能性聚合物筛选工作流程和工具是生物化学、配方科学、材料科学领域面临的一个公开挑战。