Elshafeey Ahmed Hassen, El-Dahmy Rania Moataz
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, October 6 University, Central Axis, Cairo 12585, Egypt.
Pharmaceutics. 2021 Nov 5;13(11):1869. doi: 10.3390/pharmaceutics13111869.
Paroxetine (PX) is the most potent serotonin reuptake inhibitor utilized in depression and anxiety treatment. It has drawbacks, such as having a very bitter taste, low water solubility, and undergoing extensive first pass metabolism, leading to poor oral bioavailability (<50%). This work aimed to develop and optimize palatable oral fast-dissolving films (OFDFs) loaded with a paroxetine nanosuspension. A PX nanosuspension was prepared to increase the PX solubility and permeability via the buccal mucosa. The OFDFs could increase PX bioavailability due to their rapid dissolution in saliva, without needing water, and the rapid absorption of the loaded drug through the buccal mucosa, thus decreasing the PX metabolism in the liver. OFDFs also offer better convenience to patients with mental illness, as well as pediatric, elderly, and developmentally disabled patients. The PX nanosuspension was characterized by particle size, poly dispersity index, and zeta potential. Twelve OFDFs were formulated using a solvent casting technique. A 2 × 3 full factorial design was applied to choose the optimized OFDF, utilizing Design-Expert software (Stat-Ease Inc., Minneapolis, MN, USA). The optimized OFDF (F1) had a 3.89 ± 0.19 Mpa tensile strength, 53.08 ± 1.28% elongation%, 8.12 ± 0.13 MPa Young's modulus, 17.09 ± 1.30 s disintegration time, and 96.02 ± 3.46% PX dissolved after 10 min. This optimized OFDF was subjected to in vitro dissolution, ex vivo permeation, stability, and palatability studies. The permeation study, using chicken buccal pouch, revealed increased drug permeation from the optimized OFDF; with a more than three-fold increase in permeation over the pure drug. The relative bioavailability of the optimized OFDF in comparison with the market tablet was estimated clinically in healthy human volunteers and was found to be 178.43%. These findings confirmed the success of the OFDFs loaded with PX nanosuspension for increasing PX bioavailability.
帕罗西汀（PX）是用于治疗抑郁症和焦虑症的最有效的5-羟色胺再摄取抑制剂。它存在一些缺点，比如味道极苦、水溶性低，并且经历广泛的首过代谢，导致口服生物利用度差（<50%）。这项工作旨在开发和优化负载帕罗西汀纳米混悬液的可口口服速溶膜（OFDF）。制备了PX纳米混悬液，以提高PX通过颊黏膜的溶解度和渗透性。OFDF因其能在唾液中快速溶解（无需用水）以及负载药物能通过颊黏膜快速吸收，从而减少肝脏中PX的代谢，所以可提高PX的生物利用度。OFDF还为精神疾病患者以及儿科、老年和发育障碍患者提供了更好的便利性。对PX纳米混悬液进行了粒径、多分散指数和zeta电位表征。采用溶剂浇铸技术制备了12种OFDF。利用Design-Expert软件（美国明尼阿波利斯市Stat-Ease公司）应用2×3全因子设计来选择优化的OFDF。优化后的OFDF（F1）具有3.89±0.19兆帕的拉伸强度、53.08±1.28%的伸长率、8.12±0.13兆帕的杨氏模量、17.09±1.30秒的崩解时间，以及10分钟后96.02±3.46%的PX溶解率。对这种优化后的OFDF进行了体外溶出、离体渗透、稳定性和适口性研究。使用鸡颊囊进行的渗透研究表明，优化后的OFDF药物渗透性增加；与纯药物相比，渗透性增加了三倍多。在健康人类志愿者中临床评估了优化后的OFDF与市售片剂相比的相对生物利用度，结果发现为178.43%。这些发现证实了负载PX纳米混悬液的OFDF在提高PX生物利用度方面的成功。
