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.

药物制剂是药物开发过程的关键步骤，在该过程中，活性药物成分（API）与非药物成分（赋形剂）混合，通常是时间或pH值，它在时间或pH值中释放，从而在靶组织中释放API，例如纤维素衍生物（例如纤维素衍生物），例如纤维素衍生物或glglycols intruction in commonicecipipts in Plabipient in Common comporteciprest in Plaberextecipipts in Common comprypient in Commonic extecipient in Plaberextecipipts中。聚合物降解，结晶度和机械性能可以通过更改其分子量或化学功能化来轻松调节。这些特征反过来影响了胃肠道的产品保质期，药物释放时间和有效的API浓度。 PEG或PVA的共聚物特别适合促进可溶性药物的吸收。然而，它们复杂的半结构形态随着微妙的变化和处理条件而变化，使它们的性能和API兼容性难以预测。对药物配方的聚合物摄取选择是一种耗时的，主要是试验和错误的方法。在用于小分子药物发现中通常使用的硅筛选（化学信息，机器学习）时，这种工具不容易适用于聚合物。使用具有现成参数的“计算显微镜”分子动力学（MD）技术进行赋形剂的仿真，该技术不能针对特定的赋形剂量身定制。这是由于几个因素，即缺乏自动参数化软件 - 问题开放力场，Alarge行业支持的联盟，开始解决。准确地描述聚合物灵活性是关键，因为自由度的扭转程度与聚合和结晶度直接相关。总体而言，缺乏可靠的工作流程和功能聚合物筛选的工具是在生物化学，配方科学，材料科学领域的开放挑战。