کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5549583 | 1556737 | 2016 | 9 صفحه PDF | دانلود رایگان |
Timataxel (13-(N-Boc-3-i-butylisoserinoyl-4,10-β-diacetoxy-2-α-benzoyloxy-5-β-20-epoxy-1,13-α-dihydroxy-9-oxo-19-norcyclopropa[g]tax-11-ene), used to be called TM-2, is a novel semi-synthetic promising candidate for cancer treatment. However the preformulation study showed that TM-2 was insoluble and chemically instable in water, which would limit its application. This study aimed at the preparation of Timataxel lipid microspheres (TM-2 LMs) and investigated the difference between TM-2 LMs and TM-2 solution in pharmacokinetics. In this work, the final formulation was as follows: 0.10% (w/v) TM-2; 10.00% (w/v) oil phase (long chain triglyceride:media chain triglycerideâ=â2.50%:7.50%); 1.40% (w/v) phospholipid; 0.02% (w/v) NaH2PO4; 2.25% (w/v) glycerin and water to a total volume of 100âml. The particle size distribution, content and entrapment efficacy were 205.0â±â43.3ânm, 101.00%, and 99.12%, respectively. TM-2 LMs were stable during storage at 25â°C for 3 months, even under the condition of 60â°C and 4500âlx for 10âd. Phosphatidylethanolamine (PE) in phospholipid may contribute to the stability of TM-2 LMs. The pharmacokinetic parameters for TM-2 LMs were as follows: AUC(0-â) 3663.71âµg/lâh and the clearance 2.26âl/h/kg. As for solution, these parameters were 1712.52âµg/lâh and 4.77âl/h/kg, respectively. The t1/2 of TM-2 LMs was similar to TM-2 solution. The pharmacokinetic results indicated that the AUC of TM-2 LMs was larger, the clearance was smaller than that of TM-2 solution. In a word, lipid microspheres were a promising drug delivery system for TM-2.
Graphical Abstract
Journal: Asian Journal of Pharmaceutical Sciences - Volume 11, Issue 6, December 2016, Pages 771-779