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含氨氯地平与羟丙基-β-环糊精和甲基-β-环糊精包合物的口腔崩解片的设计与评价

Design and Evaluation of Orally Dispersible Tablets Containing Amlodipine Inclusion Complexes in Hydroxypropyl-β-cyclodextrin and Methyl-β-cyclodextrin.

作者信息

Novac Marian, Musuc Adina Magdalena, Ozon Emma Adriana, Sarbu Iulian, Mitu Mirela Adriana, Rusu Adriana, Petrescu Simona, Atkinson Irina, Gheorghe Daniela, Lupuliasa Dumitru

机构信息

Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, 6 Traian Vuia Street, 020945 Bucharest, Romania.

"Ilie Murgulescu" Institute of Physical Chemistry, 202 Spl. Independentei, 060021 Bucharest, Romania.

出版信息

Materials (Basel). 2022 Jul 28;15(15):5217. doi: 10.3390/ma15155217.

Abstract

The development of new orally dispersible tablets containing amlodipine (AML) inclusion complexes in hydroxypropyl-β-cyclodextrin (HP-β-CD) and in methyl-β-cyclodextrin (Me-β-CD) was studied. The methods of obtaining amlodipine and the physical and chemical properties of the inclusion complexes using the two cyclodextrins was investigated separately. Solid inclusion complexes were obtained by three methods: kneading, coprecipitation, and lyophilization, at a molar ratio of 1:1. For comparison, a physical mixture in the same molar ratio was prepared. The aim of the complexation process was to improve the drug solubility. As the lyophilization method leads to a complete inclusion of the drug in the guest molecule cavity, for both used cyclodextrins, these types of compounds were selected as active ingredients for the design of orally dispersible tablets. Subsequently, the formulation of the orodispersible tablets containing AML-HP-β-CD and AML-Me-β-CD inclusion complexes and quality parameters of the final formulation were evaluated. The results prove that F1 and F4 formulations, based on silicified microcrystalline cellulose, which contains insignificant proportions of very small or very large particles, had the lowest moisture degree (3.52% for F1 and 4.03% for F4). All of these demonstrate their porous structure, which led to good flowability and compressibility performances. F1 and F4 formulations were found to be better to manufacture orally dispersible tablets.

摘要

研究了含氨氯地平(AML)与羟丙基-β-环糊精(HP-β-CD)和甲基-β-环糊精(Me-β-CD)包合物的新型口腔崩解片的研制。分别研究了获得氨氯地平的方法以及使用这两种环糊精的包合物的物理和化学性质。通过捏合、共沉淀和冻干三种方法,以1:1的摩尔比获得固体包合物。为作比较,制备了相同摩尔比的物理混合物。络合过程的目的是提高药物溶解度。由于冻干法能使药物完全包合在客体分子腔内,对于两种所用的环糊精,这类化合物被选作口腔崩解片设计的活性成分。随后,对含AML-HP-β-CD和AML-Me-β-CD包合物的口腔崩解片的配方及最终配方的质量参数进行了评估。结果证明,基于硅化微晶纤维素的F1和F4配方,其含有比例极低的极小或极大颗粒,具有最低的水分含量(F1为3.52%,F4为4.03%)。所有这些都表明它们的多孔结构,这导致了良好的流动性和可压缩性。发现F1和F4配方更适合制造口腔崩解片。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c6/9369640/550620dca801/materials-15-05217-sch001.jpg

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