Mawla Nihad, Hanley Sarah, Walton Karl, Kaialy Waseem, Hussain Tariq, Ward Adam, Brown Jonathan, Conway Barbara R, Timmins Peter, Asare-Addo Kofi
Department of Pharmacy, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK.
Drug Product Science and Technology, Bristol Myers Squibb, Moreton, Merseyside CH46 1QW, UK.
Pharmaceutics. 2020 Sep 18;12(9):889. doi: 10.3390/pharmaceutics12090889.
As the ingestion of drug products with alcohol could have adverse effects on the release of drugs from dosage forms, it is important to understand the mechanisms underpinning the influence on drug release by evaluating the effect of alcohol-containing media on the behaviour of pharmaceutical excipients. In this work, the effect of hydroalcoholic media containing up to 40% / absolute ethanol was evaluated, employing both the regular (CR) and direct compression grades (DC) of hypromellose. X-ray microtomography (XµT) and magnetic resonance imaging (MRI) were used as complementary techniques in determining the influence of the media composition on the ability of the CR and DC polymers to form and evolve the gel layer that controls drug release. Particle and powder properties of the polymer were characterised to determine any relationship to performance in hydroalcoholic media. Triboelectrification results showed the CR grade formulation to charge electropositively whereas the DC grade charged electronegatively. The flow properties also showed the DC grade to have a superior flow as compared to its CR counterpart. Differences in particle morphology between the grades influenced charging and flow behaviour of the powders; however, it did not seem to impact significantly either on the mechanical strength or the drug release properties of the compacted formulation using the model drug propranolol HCl. XµT and MRI imaging were successfully used as complementary techniques in determining the gel layer/hydration layer thickness measurements as the layer developed, as well as following ingress of hydroalcoholic media and its impact on the dry core. The result showed that although differences were present in the gel layer thickness potentially due to differences in particle morphology, this also did not impact significantly on the dissolution process, especially in acidic and hydroalcoholic media.
由于摄入含酒精的药品可能会对剂型中药物的释放产生不利影响，因此通过评估含酒精介质对药用辅料行为的影响来了解影响药物释放的机制非常重要。在这项工作中，评估了含高达40%/无水乙醇的水醇介质的影响，使用了羟丙甲纤维素的常规（CR）和直接压片级（DC）两种类型。X射线显微断层扫描（XµT）和磁共振成像（MRI）被用作补充技术，以确定介质组成对CR和DC聚合物形成和演变控制药物释放的凝胶层能力的影响。对聚合物的颗粒和粉末性质进行了表征，以确定其与在水醇介质中性能的任何关系。摩擦起电结果表明，CR级制剂带正电，而DC级带负电。流动性质也表明，DC级的流动性优于其CR级对应物。不同等级之间颗粒形态的差异影响了粉末的带电和流动行为；然而，这似乎对使用模型药物盐酸普萘洛尔的压实制剂的机械强度或药物释放性能没有显著影响。XµT和MRI成像成功地用作补充技术，用于确定凝胶层/水合层厚度的测量值，随着层的形成，以及跟踪水醇介质的进入及其对干芯的影响。结果表明，尽管由于颗粒形态的差异，凝胶层厚度存在差异，但这对溶解过程也没有显著影响，尤其是在酸性和水醇介质中。
