采用实验设计法研制含盐酸托莫西汀-β-环糊精包合物的小儿口腔崩解片。

Development of pediatric orally disintegrating mini-tablets containing atomoxetine hydrochloride-β-cyclodextrin inclusion complex using experimental design.

机构信息

Department of Pharmaceutical Technology, Faculty of Pharmacy, Eastern Mediterranean University, Famagusta, TR. North Cyprus, Turkey.

Department of Pharmaceutical Technology, Faculty of Pharmacy, Ankara University, Ankara, Turkey.

出版信息

Drug Dev Ind Pharm. 2022 Nov;48(11):667-681. doi: 10.1080/03639045.2022.2154787. Epub 2022 Dec 15.

DOI:10.1080/03639045.2022.2154787

PMID:36454038

Abstract

OBJECTIVE

The aim of the study was to develop and evaluate characteristics of orally disintegrating mini-tablet (ODMT) formulations including atomoxetine hydrochloride (ATO)/β-cyclodextrin (β-CD) inclusion complex for pediatric therapy of attention deficit and hyperactivity disorder (ADHD).

METHODS

Design of experiment approach was used to develop ODMTs. The ODMTs were compressed using direct compression method with two different superdisintegrants (Parteck ODT and Ac-Di-Sol) and characterized with quality control tests. dissolution and taste studies were performed.

RESULTS

The hardness and friability values of the optimized three ODMT formulations were determined as 41.7 N, 42.4 N, and 40.8 N and 0.32%, 0.29%, and 0.42%, respectively. The disintegration time of all the optimized formulations was found to be less than one minute. In addition, dissolution profiles of ATO from optimized ODMTs were determined in four different dissolution media (distilled water, pH 1.2, 6.8, and 7.4) and it was determined that the maximum dissolved ATO amount reached at the end of 20 min.

CONCLUSION

As a conclusion, the novel formulation of ODMTs with ATO/β-CD inclusion complex was successfully developed for pediatric use.

摘要

目的

本研究旨在开发和评估盐酸托莫西汀（ATO）/β-环糊精（β-CD）包合物口腔崩解迷你片剂（ODMT）制剂的特性，以用于儿科治疗注意缺陷多动障碍（ADHD）。

方法

采用实验设计方法开发 ODMT。使用两种不同的超崩解剂（Parteck ODT 和 Ac-Di-Sol）直接压缩法对 ODMT 进行压缩，并进行质量控制测试。进行了溶解和口感研究。

结果

优化的三种 ODMT 制剂的硬度和脆碎度值分别确定为 41.7 N、42.4 N 和 40.8 N，以及 0.32%、0.29%和 0.42%。所有优化制剂的崩解时间均小于一分钟。此外，在四种不同的溶解介质（蒸馏水、pH 值 1.2、6.8 和 7.4）中测定了优化的 ODMT 中 ATO 的溶解曲线，结果表明在 20 分钟结束时达到最大溶解 ATO 量。