Polymorphic Tolbutamide Oriented By Self-assembled Monolayers

The present work focused on the polymorphic crystals of tolbutamide (TB), a hypoglycemic agent, which grew on modified siloxane self-assembled monolayers (SAMs). The study of drug polymorphs is important for polymorph screening, drug stability, drug bioavailablity and drug safety.Firstly, according to the principle of structural similiarity between TB and SAMs, three kinds of SAMs were prepared and characterized on the glass surfaces: SAMs-Si-CH₂-CH₂-CH₂-NHSO₂-Ph-CH₃,SAMs- Si-CH₂-CH₂-CH₂-NHSO₂-biPh and SAMs-Si-CH₂-CH₂-CH₂-NHSO₂-Ph-CF₃.Secondly, crystallization of TB on these three SAMs at different conditions were studied by XRD, major conclusions were obtained as below:1. Metastable crystal Formâ…£appeard on SAMs-Si-CH₂-CH₂-CH₂-NHSO₂-biPh, and was stabilized by the interaction between SAMs-Si-CH₂-CH₂-CH₂-NHSO₂-biPh and TB;2. Stable crystal Formâ… andâ…¢concomitantly grow in solution, but on SAMs-Si- CH₂-CH₂-CH₂-NHSO₂-biPh, formâ… can grow in the absence of formâ…¢.3. High bioavailble crystal Formâ…¡was obtained at the following conditions:(1) SAMs-Si-CH₂-CH₂-CH₂-NHSO₂-Ph-CH₃, S=1.05, V=0.1℃/min;(2) SAMs-Si-CH₂-CH₂-CH₂-NHSO₂-biPh, S=1.2, V=0.1℃/min;(3) SAMs-Si-CH₂-CH₂-CH₂-NHSO₂-Ph-CF₃, S=1.2, V=0.1℃/min and S=1.1, V=0.5℃/min。...