Julia Monola , Elle Koivunotko , Jacopo Zini , Akseli Niemelä , Artturi Koivuniemi , Aleksi Kröger , Ossi Korhonen , Sami Valkonen , Arto Merivaara , Riina Harjumäki , Marjo Yliperttula , Jere Kekkonen
{"title":"通过拉曼光谱检测冷冻干燥诱发的乳糖变异。","authors":"Julia Monola , Elle Koivunotko , Jacopo Zini , Akseli Niemelä , Artturi Koivuniemi , Aleksi Kröger , Ossi Korhonen , Sami Valkonen , Arto Merivaara , Riina Harjumäki , Marjo Yliperttula , Jere Kekkonen","doi":"10.1016/j.ejpb.2024.114534","DOIUrl":null,"url":null,"abstract":"<div><div>Freeze-drying enables delicate, heat-sensitive biomaterials to be stored in a dry form even at room temperature. However, exposure to physicochemical stress induced by freeze-drying presents challenges for maintaining material characteristics and functionality upon reconstitution, for which reason excipients are required. Although wide variety of different excipients are available for pharmaceutical applications, their protective role in the freeze-drying is not yet fully understood. In this study, our aim was to use molecular dynamics simulations to screen the properties of different sugars and amino acids, which could be combined with plant-based nanofibrillated cellulose (NFC) hydrogel to provide protective matrix system for future freeze-drying for pharmaceuticals and biologics. The changes in the NFC-based formulations before and after freeze-drying and reconstitution were evaluated using non-invasive Timegate PicoRaman spectroscopy and traditional characterization methods. We continued to the freeze-drying with the NFC hydrogel formulations including lactose with and without glycine, which showed the highest attraction preferences on NFC surface <em>in silico.</em> This formulation enabled successful freeze-drying and subsequent reconstitution with preserved physicochemical and rheological properties. Raman spectroscopy gave us insights of the molecular-level changes during freeze-drying, especially the mutarotation of lactose. This research showed the potential of integrating <em>in silico</em> screening and non-invasive spectroscopical method to design novel biomaterial-based formulations for freeze-drying. The research provided insights of the molecular-level interactions and orientational changes of the excipients, which might be crucial in future freeze-drying applications of pharmaceuticals and biologics.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"205 ","pages":"Article 114534"},"PeriodicalIF":4.4000,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Freeze-drying-induced mutarotation of lactose detected by Raman spectroscopy\",\"authors\":\"Julia Monola , Elle Koivunotko , Jacopo Zini , Akseli Niemelä , Artturi Koivuniemi , Aleksi Kröger , Ossi Korhonen , Sami Valkonen , Arto Merivaara , Riina Harjumäki , Marjo Yliperttula , Jere Kekkonen\",\"doi\":\"10.1016/j.ejpb.2024.114534\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Freeze-drying enables delicate, heat-sensitive biomaterials to be stored in a dry form even at room temperature. However, exposure to physicochemical stress induced by freeze-drying presents challenges for maintaining material characteristics and functionality upon reconstitution, for which reason excipients are required. Although wide variety of different excipients are available for pharmaceutical applications, their protective role in the freeze-drying is not yet fully understood. In this study, our aim was to use molecular dynamics simulations to screen the properties of different sugars and amino acids, which could be combined with plant-based nanofibrillated cellulose (NFC) hydrogel to provide protective matrix system for future freeze-drying for pharmaceuticals and biologics. The changes in the NFC-based formulations before and after freeze-drying and reconstitution were evaluated using non-invasive Timegate PicoRaman spectroscopy and traditional characterization methods. We continued to the freeze-drying with the NFC hydrogel formulations including lactose with and without glycine, which showed the highest attraction preferences on NFC surface <em>in silico.</em> This formulation enabled successful freeze-drying and subsequent reconstitution with preserved physicochemical and rheological properties. Raman spectroscopy gave us insights of the molecular-level changes during freeze-drying, especially the mutarotation of lactose. This research showed the potential of integrating <em>in silico</em> screening and non-invasive spectroscopical method to design novel biomaterial-based formulations for freeze-drying. 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Freeze-drying-induced mutarotation of lactose detected by Raman spectroscopy
Freeze-drying enables delicate, heat-sensitive biomaterials to be stored in a dry form even at room temperature. However, exposure to physicochemical stress induced by freeze-drying presents challenges for maintaining material characteristics and functionality upon reconstitution, for which reason excipients are required. Although wide variety of different excipients are available for pharmaceutical applications, their protective role in the freeze-drying is not yet fully understood. In this study, our aim was to use molecular dynamics simulations to screen the properties of different sugars and amino acids, which could be combined with plant-based nanofibrillated cellulose (NFC) hydrogel to provide protective matrix system for future freeze-drying for pharmaceuticals and biologics. The changes in the NFC-based formulations before and after freeze-drying and reconstitution were evaluated using non-invasive Timegate PicoRaman spectroscopy and traditional characterization methods. We continued to the freeze-drying with the NFC hydrogel formulations including lactose with and without glycine, which showed the highest attraction preferences on NFC surface in silico. This formulation enabled successful freeze-drying and subsequent reconstitution with preserved physicochemical and rheological properties. Raman spectroscopy gave us insights of the molecular-level changes during freeze-drying, especially the mutarotation of lactose. This research showed the potential of integrating in silico screening and non-invasive spectroscopical method to design novel biomaterial-based formulations for freeze-drying. The research provided insights of the molecular-level interactions and orientational changes of the excipients, which might be crucial in future freeze-drying applications of pharmaceuticals and biologics.
期刊介绍:
The European Journal of Pharmaceutics and Biopharmaceutics provides a medium for the publication of novel, innovative and hypothesis-driven research from the areas of Pharmaceutics and Biopharmaceutics.
Topics covered include for example:
Design and development of drug delivery systems for pharmaceuticals and biopharmaceuticals (small molecules, proteins, nucleic acids)
Aspects of manufacturing process design
Biomedical aspects of drug product design
Strategies and formulations for controlled drug transport across biological barriers
Physicochemical aspects of drug product development
Novel excipients for drug product design
Drug delivery and controlled release systems for systemic and local applications
Nanomaterials for therapeutic and diagnostic purposes
Advanced therapy medicinal products
Medical devices supporting a distinct pharmacological effect.