Department of Pharmacy and Pharmacology, University of Bath, Bath, United Kingdom.
Pharmaceutical Technology & Development, AstraZeneca, Macclesfield, United Kingdom.
Int J Pharm. 2020 Mar 15;577:119080. doi: 10.1016/j.ijpharm.2020.119080. Epub 2020 Jan 24.
Superdisintegrants are a key excipient used in immediate release formulations to promote fast tablet disintegration, therefore understanding the impact of superdisintegrant variability on product performance is important. The current study examined the impact of superdisintegrant critical material attributes (viscosity for sodium starch glycolate (SSG), particle size distribution (PSD) for croscarmellose sodium (CCS)) on their performance (swelling) and on drug dissolution using surface dissolution UV imaging. Acidic and basic pharmacopoeia (compendial) media were used to assess the role of varying pH on superdisintegrant performance and its effect on drug dissolution. A highly soluble (paracetamol) and a poorly soluble (carbamazepine) drug were used as model compounds and drug compacts and drug-excipient compacts were prepared for the dissolution experiments. The presence of a swelled SSG or CCS layer on the compact surface, due to the fast excipient hydration capacity, upon contact with dissolution medium was visualized. The swelling behaviour of superdisintegrants depended on excipient critical material attributes and the pH of the medium. Drug dissolution was faster in presence compared to superdisintegrant absence due to improved compact wetting or compact disintegration. The improvement in drug dissolution was less pronounced with increasing SSG viscosity or CCS particle size. Drug dissolution was slightly more complete in basic compared to acidic conditions in presence of the studied superdisintegrants for the highly soluble drug attributed to the increased excipient hydration capacity and the fast drug release through the swelled excipient structure. The opposite was observed for the poorly soluble drug as potentially the improvement in drug dissolution was compromised by drug release from the highly swelled structure. The use of multivariate data analysis revealed the influential role of excipient and drug properties on the impact of excipient variability on drug dissolution.
超级崩解剂是速释制剂中关键的赋形剂，用于促进片剂快速崩解，因此了解超级崩解剂变异性对产品性能的影响非常重要。本研究通过表面溶解紫外成像，考察了超级崩解剂关键材料属性（交联羧甲基纤维素钠（CCS）的粘度、交联羧甲淀粉钠（SSG）的粒径分布（PSD））对其性能（溶胀）和药物溶出度的影响。采用酸性和碱性药典（法定）介质评估了不同 pH 值对超级崩解剂性能的作用及其对药物溶出度的影响。选用高溶解性（扑热息痛）和低溶解性（卡马西平）药物作为模型化合物和药物压片，并为溶出实验制备了药物-赋形剂压片和药物-赋形剂混合物压片。在接触溶出介质时，由于快速赋形剂水合能力，在压片表面上观察到 SSG 或 CCS 层的溶胀。超级崩解剂的溶胀行为取决于赋形剂关键材料属性和介质的 pH 值。由于改善了压片的润湿或压片崩解，与不存在超级崩解剂相比，存在超级崩解剂时药物溶出更快。随着 SSG 粘度或 CCS 粒径的增加，药物溶出度的提高程度较小。在研究的超级崩解剂存在下，与酸性条件相比，在碱性条件下，高溶解性药物的药物溶出度略高，这归因于增加的赋形剂水合能力和通过溶胀的赋形剂结构快速释放药物。对于低溶解性药物，情况则相反，因为药物从高度溶胀的结构中释放出来，可能会损害药物溶出度的提高。多变量数据分析显示了赋形剂和药物性质对赋形剂变异性对药物溶出度影响的重要作用。
