{"title":"Mechanisms of drug release from a melt-milled, poorly soluble drug substance.","authors":"Dominik Sleziona, David R Ely, Markus Thommes","doi":"10.1016/j.xphs.2024.10.016","DOIUrl":null,"url":null,"abstract":"<p><p>Increasing the dissolution kinetics of low aqueous soluble drugs is one of the main priorities in drug formulation. New strategies must be developed, which should consider the two main dissolution mechanisms: surface reaction and diffusion. One promising tool is the so-called solid crystal suspension, a solid dispersion consisting of purely crystalline substances. In this concept, reducing the drug particle size and embedding the particles in a hydrophilic excipient increases the dissolution kinetics. Therefore, a solid crystal suspension containing submicron drug particles was produced via a modified stirred media milling process. A geometrical phase-field approach was used to model the dissolution behavior of the drug particles. A carrier material, xylitol, and the model drug substance, griseofulvin, were ground in a pearl mill. The in-vitro dissolution profile of the product was modeled to gain a deep physical understanding of the dissolution process. The used numerical tool has the potential to be a valuable approach for predicting the dissolution behavior of newly developed formulation strategies.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of pharmaceutical sciences","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.xphs.2024.10.016","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Increasing the dissolution kinetics of low aqueous soluble drugs is one of the main priorities in drug formulation. New strategies must be developed, which should consider the two main dissolution mechanisms: surface reaction and diffusion. One promising tool is the so-called solid crystal suspension, a solid dispersion consisting of purely crystalline substances. In this concept, reducing the drug particle size and embedding the particles in a hydrophilic excipient increases the dissolution kinetics. Therefore, a solid crystal suspension containing submicron drug particles was produced via a modified stirred media milling process. A geometrical phase-field approach was used to model the dissolution behavior of the drug particles. A carrier material, xylitol, and the model drug substance, griseofulvin, were ground in a pearl mill. The in-vitro dissolution profile of the product was modeled to gain a deep physical understanding of the dissolution process. The used numerical tool has the potential to be a valuable approach for predicting the dissolution behavior of newly developed formulation strategies.
期刊介绍:
The Journal of Pharmaceutical Sciences will publish original research papers, original research notes, invited topical reviews (including Minireviews), and editorial commentary and news. The area of focus shall be concepts in basic pharmaceutical science and such topics as chemical processing of pharmaceuticals, including crystallization, lyophilization, chemical stability of drugs, pharmacokinetics, biopharmaceutics, pharmacodynamics, pro-drug developments, metabolic disposition of bioactive agents, dosage form design, protein-peptide chemistry and biotechnology specifically as these relate to pharmaceutical technology, and targeted drug delivery.