Maestrelli Francesca, Cirri Marzia, Mennini Natascia, Fiani Silvia, Stoppacciaro Beatrice, Mura Paola
Department of Chemistry, School of Human Health Sciences, University of Florence, Via Ugo Schiff 6, 50019 Florence, Italy.
Pharmaceutics. 2024 May 9;16(5):633. doi: 10.3390/pharmaceutics16050633.
New oral tablets of nebivolol have been developed aiming to improve, by cyclodextrin (CD) complexation, its low solubility/dissolution properties-the main reason behind its poor/variable oral bioavailability. Phase-solubility studies, performed using βCD and highly-soluble βCD-derivatives, indicated sulfobutylether-βCD (SBEβCD) as the best solubilizing/complexing agent. Solid drug-SBEβCD systems were prepared by different methods and characterized for solid-state and dissolution properties. The coevaporated product was chosen for tablet development since it provided the highest dissolution rate (100% increase in dissolved drug at 10 min) and almost complete drug amorphization/complexation. The developed tablets reached the goal, allowing us to achieve 100% dissolved drug at 60 min, compared to 66% and 64% obtained, respectively, with a reference tablet without CD and a commercial tablet. However, the percentage dissolved after 10 min from such tablets was only 10% higher than the reference. This was ascribed to the potential binding/compacting abilities of SBEβCD, reflected in the greater hardness and longer disintegration times of the new tablets than the reference (7.64 vs. 1.06 min). A capsule formulation with the same composition of nebivolol-SBEβCD tablets showed about a 90% increase in dissolved drug after 5 min compared to the reference tablet, and reached 100% dissolved drug after only 20 min.
已开发出奈必洛尔新的口服片剂，旨在通过环糊精（CD）包合作用改善其低溶解度/溶出特性，这是其口服生物利用度差/不稳定的主要原因。使用β-环糊精（βCD）和高溶性βCD衍生物进行的相溶解度研究表明，磺丁基醚-β-环糊精（SBEβCD）是最佳的增溶/包合剂。通过不同方法制备了固体药物-SBEβCD体系，并对其固态和溶出特性进行了表征。选择共蒸发产物用于片剂开发，因为它具有最高的溶出速率（10分钟时溶解药物增加100%）以及几乎完全的药物非晶化/包合。所开发的片剂达到了目标，使我们能够在60分钟时实现100%的药物溶解，相比之下，不含CD的参比片剂和市售片剂分别达到了66%和64%。然而，这些片剂在10分钟后的溶解百分比仅比参比片剂高10%。这归因于SBEβCD潜在的结合/压实能力，这体现在新片剂比参比片剂具有更大的硬度和更长的崩解时间（7.64分钟对1.06分钟）。与奈必洛尔-SBEβCD片剂组成相同的胶囊制剂在5分钟后的溶解药物比参比片剂增加约90%，并且仅在20分钟后就达到了100%的药物溶解。
