Duarte Íris, Santos José Luís, Pinto João F, Temtem Márcio
iMed - Research Institute for Medicines and Pharmaceutical Sciences, University of Lisbon, Faculty of Pharmacy, Av. Prof. Gama Pinto, 1649-003, Lisboa, Portugal.
Pharm Res. 2015 Jan;32(1):222-37. doi: 10.1007/s11095-014-1457-5. Epub 2014 Aug 19.
To present a new screening methodology intended to be used in the early development of spray-dried amorphous solid dispersions.
A model that combines thermodynamic, kinetic and manufacturing considerations was implemented to obtain estimates of the miscibility and phase behavior of different itraconazole-based solid dispersions. Additionally, a small-scale solvent casting protocol was developed to enable a fast assessment on the amorphous stability of the different drug-polymer systems. Then, solid dispersions at predefined drug loads were produced in a lab-scale spray dryer for powder characterization and comparison of the results generated by the model and solvent cast samples.
The results obtained with the model enabled the ranking of the polymers from a miscibility standpoint. Such ranking was consistent with the experimental data obtained by solvent casting and spray drying. Moreover, the range of optimal drug load determined by the model was as well consistent with the experimental results.
The screening methodology presented in this work showed that a set of amorphous formulation candidates can be assessed in a computer model, enabling not only the determination of the most suitable polymers, but also of the optimal drug load range to be tested in laboratory experiments. The set of formulation candidates can then be further fine-tuned with solvent casting experiments using a small amount of API, which will then provide the decision for the final candidate formulations to be assessed in spray drying experiments.
介绍一种旨在用于喷雾干燥无定形固体分散体早期开发的新筛选方法。
实施一个结合热力学、动力学和制造因素的模型，以获得不同伊曲康唑基固体分散体的混溶性和相行为估计值。此外，开发了一种小规模溶剂浇铸方案，以便能够快速评估不同药物-聚合物体系的无定形稳定性。然后，在实验室规模的喷雾干燥器中制备预定义药物载量的固体分散体，用于粉末表征，并比较模型和溶剂浇铸样品产生的结果。
从混溶性角度来看，模型获得的结果能够对聚合物进行排序。这种排序与通过溶剂浇铸和喷雾干燥获得的实验数据一致。此外，模型确定的最佳药物载量范围也与实验结果一致。
本研究中提出的筛选方法表明，一组无定形制剂候选物可在计算机模型中进行评估，不仅能够确定最合适的聚合物，还能确定在实验室实验中测试的最佳药物载量范围。然后，可以使用少量活性药物成分通过溶剂浇铸实验对制剂候选物组进行进一步微调，这将为在喷雾干燥实验中评估的最终候选制剂提供决策依据。
