Isreb Mohammad, Chalkia Marianiki, Gough Timothy, Forbes Robert Thomas, Timmins Peter
School of Pharmacy and Medical Sciences, University of Bradford, Bradford BD7 1DP, UK.
School of Engineering and Informatics, University of Bradford, Bradford BD7 1DP, UK.
Polymers (Basel). 2022 Aug 27;14(17):3527. doi: 10.3390/polym14173527.
The viscoelastic nature of polymeric formulations utilised in drug products imparts unique thermomechanical attributes during manufacturing and over the shelf life of the product. Nevertheless, it adds to the challenge of understanding the precise mechanistic behaviour of the product at the microscopic and macroscopic level during each step of the process. Current thermomechanical and rheological characterisation techniques are limited to assessing polymer performance to a single phase and are especially hindered when the polymers are undergoing thermomechanical transitions. Since pharmaceutical processing can occur at these transition conditions, this study successfully proposes a thermomechanical characterisation approach combining both mechanical and rheological data to construct a comprehensive profiling of polymeric materials spanning both glassy and rubbery phases. This approach has been used in this study to assess the mechanical and rheological behaviour of heterogenous polymer blends of hydroxypropyl cellulose (HPC) and hydroxypropyl methylcellulose (HPMC) over a shearing rate range of 0.1-100 s and a temperature range of 30-200 °C. The results indicate that HPC and HPMC do not appear to interact when mixing and that their mixture exhibits the mechanistic properties of the two individual polymers in accordance with their ratio in the mixture. The ability to characterise the behaviour of the polymers and their mixtures before, throughout, and after the glassy to rubbery phase transition by application of the combined techniques provides a unique insight towards a quality-by-design approach to this and other polymer-based solid dosage forms, designed with the potential to accelerate their formulation process through obviating the need for multiple formulation trials.
药品中使用的聚合物制剂的粘弹性在产品制造过程和保质期内赋予其独特的热机械特性。然而，这增加了在过程的每个步骤中从微观和宏观层面理解产品精确机械行为的挑战。当前的热机械和流变学表征技术仅限于评估聚合物在单一相中的性能，当聚合物经历热机械转变时尤其受到阻碍。由于药物加工可能在这些转变条件下发生，本研究成功提出了一种结合机械和流变数据的热机械表征方法，以构建跨越玻璃态和橡胶态的聚合物材料的综合概况。本研究中已使用该方法评估羟丙基纤维素（HPC）和羟丙基甲基纤维素（HPMC）的非均相聚合物共混物在0.1 - 100 s的剪切速率范围和30 - 200°C的温度范围内的机械和流变行为。结果表明，HPC和HPMC在混合时似乎不相互作用，并且它们的混合物根据其在混合物中的比例表现出两种单独聚合物的机械性能。通过应用组合技术来表征聚合物及其混合物在玻璃态到橡胶态转变之前、过程中和之后的行为的能力，为这种以及其他基于聚合物的固体剂型的质量源于设计方法提供了独特的见解，有望通过避免多次制剂试验来加速其制剂过程。
