Orally Disintegrating Film of High-Dose BCS II Drug by Hot Melt Extrusion through Design of Experiment,Journal of Pharmaceutical Innovation

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Orally Disintegrating Film of High-Dose BCS II Drug by Hot Melt Extrusion through Design of Experiment
Journal of Pharmaceutical Innovation ( IF 2.7 ) Pub Date : 2022-04-02 , DOI: 10.1007/s12247-022-09631-3
Apoorva Phadke ₁ , Purnima Amin ₁

Affiliation

Purpose

Incorporating high-dose insoluble drugs in quick release films has been a challenge. Given the limited size and shape of an orally disintegrating film, it becomes difficult to load a large amount of drug, especially when the drug is not freely soluble. Hot melt extrusion (HME) technology can be effectively utilized to address this issue. Due to the variety of limitations associated with solvent casting, there is an unmet need for an eco-friendly, patient compliant and continuous manufacturing process for the manufacturing of ODF.

Method

The current research work utilizes HME for the continuous manufacture of oral soluble film of a high-dose BCS II, a nonsteroidal anti-inflammatory drug, nimesulide, for pain management. The formulation variables can be analysed by quality by design (QbD)-based design of experiment (DoE) to investigate the effect of the formulation variables on the quality of the final formulation. Analysis by DoE provided a sound statistical basis for choosing the concentration of the formulation variables to achieve optimized disintegration time, plasticity and drug release.

Result

The optimized formulation was evaluated for mechanistic attributes, physicochemical properties, in vitro release and stability. The resultant formulation was stable with optimum mechanical strength and release profile.

Conclusion

ODF with percent drug loading as high as 21.73% w/w was formulated and analysed successfully by QbD-based DoE using HME. The results confirmed the suitability of the HME technique for the formulation of ODFs with high-dose BCS class 2 drugs.

中文翻译：

实验设计热熔挤出大剂量BCSⅡ药物口腔崩解膜

目的

在快速释放薄膜中加入高剂量不溶性药物一直是一个挑战。鉴于口腔崩解膜的尺寸和形状有限，装载大量药物变得困难，特别是当药物不能自由溶解时。热熔挤出（HME）技术可以有效地解决这个问题。由于与溶剂浇铸相关的各种限制，对用于制造 ODF 的环保、患者顺从和连续制造工艺的需求未得到满足。

方法

目前的研究工作利用 HME 连续制造高剂量 BCS II（一种非甾体抗炎药尼美舒利）的口服可溶性薄膜，用于疼痛管理。配方变量可以通过基于质量源于设计 (QbD) 的实验设计 (DoE) 进行分析，以研究配方变量对最终配方质量的影响。DoE 的分析为选择配方变量的浓度以实现优化的崩解时间、可塑性和药物释放提供了良好的统计基础。