Improved oral absorption of tacrolimus by a solid dispersion with hypromellose and sodium lauryl sulfate

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• 作者：Hyuck Jun Jung ; Hye In Ahn ; Ji Yeon Park ; Myoung Jin Ho ; Dae Ro Lee ; Ha Ra Cho ; Jun Seo Park ; Yong Seok Choi ; Myung Joo Kang ; ^{kangmj@dankook.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Tacrolimus ; Solid dispersion ; Hydroxypropyl methylcellulose ; Sodium lauryl sulfate ; Dissolution ; Bioavailability
• 刊名：International Journal of Biological Macromolecules
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：83
• 期：Complete
• 页码：282-287
• 全文大小：815 K

文摘

A novel surfactant-incorporated hydroxypropyl methylcellulose (HPMC) solid dispersion (SD) system was constructed in order to facilitate the release rate and oral absorption of tacrolimus (FK506), a poorly water-soluble immunosuppressant. Several emulsifiers including sodium lauryl sulfate (SLS), as drug release promotors, were employed with HPMC to fabricate SD using the solvent wetting method. The solid state characteristics using differential scanning calorimetry and X-ray powder diffraction, revealed that FK506 was molecularly distributed within all dispersions in amorphous form. The dissolution rates of FK506 in SLS-incorporated SDs were much higher than those in SDs prepared with HPMC alone, and even with stearoyl polyoxyl-32 glycerides or tocopheryl polyethylene glycol 1000 succinate. In particular, the greatest dissolution enhancement was obtained from the SD consisting of the drug, HPMC, and SLS in a weight ratio of 1:1:3, providing a 50-fold higher drug concentration within 15 min, compared with HPMC SD. In vivo absorption study in rats demonstrates that the optimized formula remarkably increased the oral absorption of FK506, providing about 4.0-fold greater bioavailability (p < 0.05) compared with the marketed product (Prograf^®, Astellas Pharma). These data suggest that a novel SLS/HPMC SD may be an advantageous dosage form of FK506, boosting the dissolution and absorption in gastrointestinal tract.