Development of a zero-order sustained-release tablet containing mesalazine and budesonide intended to treat the distal gastrointestinal tract in inflammatory bowel disease

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• 作者：Bahez Gareb^a ; ^b ; ^{b.gareb01@umcg.nl" class="auth_mail" title="E-mail the corresponding author} ; Anko C. Eissens^a ; ^{a.c.eissens@rug.nl" class="auth_mail" title="E-mail the corresponding author} ; Jos G.W. Kosterink^b ; ^c ; ^{j.g.w.kosterink@umcg.nl" class="auth_mail" title="E-mail the corresponding author} ; Hendrik W. Frijlink^a ; ^{h.w.frijlink@rug.nl" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Drug targeting ; 5-Aminosalicylic acid ; Budesonide ; ColoPulse
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：103
• 期：Complete
• 页码：32-42
• 全文大小：567 K

文摘

Ulcerative colitis (UC) and Crohn’s disease (CD) are diseases affecting the gastrointestinal tract. Treatment depends on the severity of the disease, site of inflammation, and patient’s response. The aim of this study was to develop a zero-order sustained-release tablet containing both the anti-inflammatory drugs mesalazine and budesonide as a new treatment option for ileo-colonic CD and UC. Tablets were attained by wet granulation with hydroxypropyl methylcellulose and direct compression. Our newly developed tablet core was coated with different ColoPulse® coating thicknesses and the mesalazine and budesonide release profiles were investigated in a 600-min gastrointestinal simulation system (GISS) experiment, together with commercially available MMX®-mesalazine and MMX®-budesonide. Lag-time, release rate (k₀), completeness of release, and zero-order correlation coefficient (R²₀) could be manipulated by varying ColoPulse® coating thickness. Our newly developed combination preparation (C[4.92]) complied with all conducted European Pharmacopoeia tests as well as an accelerated 6-month stability test and had a lag-time of 250 min (simulated ileum targeted), a linear release profile (mesalazine R²₀ = 0.9002; budesonide R²₀ = 0.9481), and drug release of 100% mesalazine and 77% budesonide. Like C[4.92], MMX®-mesalazine had a linear (R²₀ = 0.9883) and complete release profile (96%). However, C[4.92] lag-time was longer (250 vs. 210 min), assuring simulated ileum specificity. Remarkably, MMX®-budesonide lag-time was 480 min and release was only 7% with a linear character (R²₀ = 0.9906). The in vitro results suggest that MMX®-budesonide effectiveness may be improved if budesonide release in the aqueous phase would be increased and that C[4.92] is a potential, new treatment option for ileo-colonic CD and UC.