Confinement Effects on Drugs in Thermally Hydrocarbonized Porous Silicon

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• 作者：Ermei M盲kil盲 ; M贸nica P. A. Ferreira ; Henri Kivel盲 ; Sanna-Mari Niemi ; Alexandra Correia ; Mohammad-Ali Shahbazi ; Jussi Kauppila ; Jouni Hirvonen ; H茅lder A. Santos ; Jarno Salonen
• 刊名：Langmuir
• 出版年：2014
• 出版时间：March 4, 2014
• 年：2014
• 卷：30
• 期：8
• 页码：2196-2205
• 全文大小：463K
• 年卷期：v.30,no.8(March 4, 2014)
• ISSN：1520-5827

文摘

Thermally hydrocarbonized porous silicon (THCPSi) microparticles were loaded with indomethacin (IMC) and griseofulvin (GSV) using three different payloads between 6.2鈥?9.5 and 6.2鈥?1.4 wt %, respectively. The drug loading parameters were selected to avoid crystallization of the drug molecules on the external surface of the particles that would block the pore entrances. The successfulness of the loadings was verified with TG, DSC, and XRPD measurements. The effects of the confinement of IMC and GSV into the small mesopores of THCPSi were analyzed with helium pycnometry, FTIR, and NMR spectroscopy. The results showed the density of the THCPSi loaded drugs to be ca. 10% lower than the bulk crystalline forms, while a melt quenched amorphous drugs showed a density reduction of 3鈥?.5%. DSC and FTIR results confirmed that the drugs reside in an amorphous form within the THCPSi pores. Similar results were obtained with NMR, which also indicated that IMC may reside as both amorphous clusters and individual molecules within the pores. The ¹H transverse relaxation times (T₂) of amorphous and THCPSi loaded drugs showed IMC relaxation times of 0.28 ms for both the cases, whereas for GSV the values were 0.32 and 0.39 ms, respectively, indicating similar limited mobility in both cases. The results indicated that strong drug鈥揷arrier interactions were not necessary for stabilizing the amorphous state of the adsorbed drug. Dissolution tests using biorelevant media, fasted state simulated intestinal fluid (FaSSIF) and simulated gastric fluid (SGF), showed that THCPSi-loaded IMC and GSV were rapidly released in FaSSIF with comparable rates to the amorphous forms, whereas in SGF the THCPSi reduced the pH dependency in the dissolution of IMC.