Combined use of cyclodextrins and hydroxypropylmethylcellulose stearoxy ether (SangeloseA®) for the preparation of orally disintegrating tablets of type-2 antidiabetes agent glimepiride
Combined use of cyclodextrins and hydroxypropylmethylcellulose stearoxy ether (SangeloseA®) for the preparation of orally disintegrating tablets of type-2 antidiabetes agent glimepiride
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DOI：
10.1007/s10847-014-0386-6
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发表时间：
2014-10-01
影响因子：
2.3
通讯作者：
Uekama, K.
中科院分区：
文献类型：
--
作者：
Aldawsari, H.;Altaf, A.;Uekama, K.
尽管口腔崩解片(ODTS)的配方最近取得了进展，但提高药物在崩解后的吞咽能力的努力一直有限。本研究探讨了环糊精(CyDS)与功能性药物载体羟丙甲基纤维素硬脂氧基醚(Sangelose(A(R)联合使用的可行性，以提高ODTS的可用性。格列美脲是一种有效的第三代降糖药，因其水溶性差，消除半衰期较短而被用作模型药物。采用直接压片法制备了格列美脲(A(R))片剂，考察了片剂的各项性质。在α-CyD和β-CyD的情况下，获得了符合ODT标准的具有适当硬度的较短的崩解时间。另一方面，γ-Cyd、HP-β-Cyd和Hb-β-Cyd增加了片剂的硬度和崩解时间。流变学评价表明，除了伽马-环糊精外，环孢菌素在片剂崩解后显著降低了液体的粘度，表明易于吞咽。这归因于桑格糖(A(R))的疏水硬脂酰基部分在溶解后与环状结构络合，从而抑制了桑格糖(A(R))的聚合物-聚合物相互作用，降低了溶液的粘度。用溶解度法研究了格列美脲与α-和β-环状化合物的相互作用，结果表明格列美脲与这些环状化合物形成了水溶性的络合物。在这里获得的结果表明，与伽马-Cyd、HP-β-Cyd和HB-β-Cyd相比，α-Cyd和β-Cyd对于以Sangelose(A(R))为基础的ODT配方特别有用，因为含有α-Cyd和β-Cyd的片剂崩解时间短，它们对Sangelose(A(R))溶液的剪切稀释作用以及它们对药物的增溶作用。
Despite recent advances in the formulation of orally disintegrating tablets (ODTs), the efforts to enhance the swallowing of the drug after disintegration have been limited. In this study, the feasibility of the combined use of cyclodextrins (CyDs) and a functional drug carrier, hydroxypropylmethylcellulose stearoxy ether (Sangelose(A (R))) was investigated to improve usability of ODTs. Glimepiride, a potent third generation hypoglycemic agent for type 2 diabetes was used as a model drug, because it is poorly water-soluble and elimination half life is fairly short. The direct compression method was employed for the preparation of glimepiride tablets, containing CyDs and Sangelose(A (R)), and various characteristics of the tablets were examined. In the cases of alpha-CyD and beta-CyD, a short disintegration time with an appropriate hardness was obtained, complying with ODT criteria. On the other hand, gamma-CyD, HP-beta-CyD and HB-beta-CyD increased in the hardness and disintegration time of the tablets. The rheological evaluation revealed that CyDs, except gamma-CyD, significantly reduced the viscosity of the fluids after disintegration of the tablets, suggesting an ease of swallowing. This was ascribable to the complexation of the hydrophobic stearoyl moiety of Sangelose(A (R)) with CyDs after dissolution, leading to the inhibition of the polymer-polymer interaction of Sangelose(A (R)) and to the decrease in viscosity of the solution. The interaction of glimepiride with alpha- and beta-CyDs was studied by the solubility method, demonstrating that glimepiride formed water-soluble complexes with these CyDs. Results obtained here suggested that alpha-CyD and beta-CyD can be particularly useful for the Sangelose(A (R))-based ODT formulation, compared to gamma-CyD, HP-beta-CyD and HB-beta-CyD, because of the short disintegration time of the tablets containing alpha-CyD and beta-CyD, their shear-thinning effect on Sangelose(A (R)) solutions and their solubility enhancing effect on the drug.