Poloxamer 407 microspheres for orotransmucosal drug delivery. Part II: In vitro/in vivo evaluation
Poloxamer 407 microspheres for orotransmucosal drug delivery. Part II: In vitro/in vivo evaluation
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DOI：
10.1016/j.ijpharm.2010.08.018
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发表时间：
2010-11-15
影响因子：
5.8
通讯作者：
Chetoni, P.
中科院分区：
文献类型：
--
作者：
Monti, D.;Burgalassi, S.;Chetoni, P.
本研究的目的是评价基于泊洛沙姆407的新型微球作为阿替洛尔(AT)的口腔给药系统，无论是单独使用还是与格列菲尔(R)50/13混合使用。采用喷雾凝聚法制备了AT微球，并考察了AT通过纤维素膜的体外释放和猪口腔黏膜的体外渗透。对微粒进行测试或直接压实以获得片剂。为了比较，考察了物理混合物、物理混合物的片剂和AT溶液。最后，将这些微粒在兔体内舌下注射，以评价AT的药代动力学，并与市场上的口服片剂(参考文献)进行比较。与药物溶液相比，微球通过合成膜的AT释放延迟，当微球含有泊洛沙姆作为唯一佐剂时更明显；该处方促进了AT的经粘膜渗透。泊洛沙姆对相应物理混合物的渗透实验证实了泊洛沙姆的促透作用。压片既阻碍了药物通过纤维素膜的释放，也阻碍了药物的经粘膜渗透。体内研究表明，尽管药物剂量较低，但微球制剂的绝对生物利用度高于参比制剂，提示AT微球或经粘膜给药可能减少剂量。(C)2010爱思唯尔B.V.保留所有权利。
Aim of this research was to evaluate novel microspheres based on poloxamer 407, alone or in mixture with Gelucire (R) 50/13, as possible buccal delivery system for atenolol (AT). The microspheres have been prepared by spray congealing and investigated to assess AT in vitro delivery through cellulose membranes and ex vivo permeation using porcine buccal mucosa. The microparticles were tested as such or directly compacted to obtain tablets. For comparison the physical mixtures, tablets of the physical mixtures and an AT solution were examined. Finally, the microparticles were sublingually administered in rabbits to evaluate AT pharmacokinetics compared to a market oral tablet (reference). The AT release from microspheres through the synthetic membrane was delayed with respect to the drug solution, more markedly when microparticles contained poloxamer as unique adjuvant; this formulation enhanced AT transmucosal permeation. The enhancement effect of poloxamer was confirmed by the permeation experiments on the corresponding physical mixture. Tabletting hindered both release through cellulose membranes and transmucosal permeation of drug. In vivo studies revealed that the absolute bioavailability of microsphere formulations was higher than that of reference in spite of a lower dosage of drug, suggesting a possible dose reduction by AT microparticles orotransmucosal administration. (C) 2010 Elsevier B.V. All rights reserved.