Shahien Mona M, Alshammari Alia, Ibrahim Somaia, Ahmed Enas Haridy, Atia Hanan Abdelmawgoud, Elariny Hemat A, Abdallah Marwa H
Department of Pediatrics, College of Medicine, University of Ha'il, Ha'il 81442, Saudi Arabia.
Department of Pharmaceutics, College of Pharmacy, University of Ha'il, Ha'il 81442, Saudi Arabia.
Gels. 2024 Sep 23;10(9):608. doi: 10.3390/gels10090608.
Sulpiride (Sul) is a medication that blocks dopamine D receptors. It is used to treat gastrointestinal disturbances and has antipsychotic effects depending on the dose given. Sulpiride is subject to P-glycoprotein efflux, resulting in limited bioavailability and erratic absorption. Hence, the aim of this study was to generate a glycerosomal in situ gel of sulpiride for intranasal administration, specifically targeting children with schizophrenia who may have difficulty swallowing traditional solid medications, for enhancing its bioavailability. This study aimed to demonstrate the efficacy of intranasal administration of glycerin-encapsulated lipid-nanovesicles (glycerosomes) mixed with in situ gels for prolonged release of anti-psychotic medication. A Box-Behnken design was utilized to create sulpiride-loaded glycerosomes (Sul-GMs), with the lipid amount (A), glycerin concentration (B), and sonication time (C) acting as independent variables. Their impact on the entrapment efficiency, EE% (Y), and in vitro drug release (Y) were evaluated. The sulpiride EE% showed an increase when the glycerin concentration was raised to 25% /. Nevertheless, when the glycerin concentration was raised to 40% /, there was a notable decrease in the EE%. The optimized glycerosome was added to pH triggered carbopol 974P in situ gel formulations including HPMC K15M with different concentrations. The in situ gel formulation (G3) comprising 0.6% carbopol 974P and 0.6% hydroxypropyl methyl cellulose-K15M (HPMC K15M) demonstrated suitable pH, viscosity, desired gel strength, spreadability, and mucoadhesive strength. Consequently, it was selected for in vitro study, ex vivo permeation investigation, and in vivo evaluations. The glycerosomal in situ gel exhibited favorable ex vivo permeability of SU when applied to the nasal mucosa. The pharmacokinetic investigation revealed that the optimized Sul-loaded glycerosomal in situ gel exhibited a significant fourfold and twofold enhancement in systemic bioavailability compared to both the control gel and the commercially available formulation. Finally, the intranasal administration of Sul-loaded glycerosomal in situ gel is a promising alternative to oral treatment for pediatric patients with psychosis.
舒必利（Sul）是一种阻断多巴胺D受体的药物。它用于治疗胃肠道紊乱，根据给药剂量具有抗精神病作用。舒必利会受到P-糖蛋白外排的影响，导致生物利用度有限且吸收不稳定。因此，本研究的目的是制备一种用于鼻腔给药的舒必利甘油osomal原位凝胶，特别针对可能难以吞咽传统固体药物的精神分裂症儿童，以提高其生物利用度。本研究旨在证明鼻腔给药甘油包裹的脂质纳米囊泡（甘油osomes）与原位凝胶混合用于抗精神病药物的长效释放的有效性。采用Box-Behnken设计制备负载舒必利的甘油osomes（Sul-GMs），脂质含量（A）、甘油浓度（B）和超声处理时间（C）作为自变量。评估它们对包封率EE%（Y）和体外药物释放（Y）的影响。当甘油浓度提高到25%/时，舒必利的EE%有所增加。然而，当甘油浓度提高到40%/时，EE%显著下降。将优化后的甘油osome添加到不同浓度的含羟丙基甲基纤维素-K15M（HPMC K15M）的pH触发型卡波姆974P原位凝胶制剂中。包含0.6%卡波姆974P和0.6%羟丙基甲基纤维素-K15M（HPMC K15M）的原位凝胶制剂（G3）表现出合适的pH值、粘度、所需的凝胶强度、铺展性和粘膜粘附强度。因此，它被选用于体外研究、离体渗透研究和体内评估。当应用于鼻黏膜时，甘油osomal原位凝胶对舒必利表现出良好的离体渗透性。药代动力学研究表明，与对照凝胶和市售制剂相比，优化后的负载舒必利的甘油osomal原位凝胶的全身生物利用度显著提高了四倍和两倍。最后，对于患有精神病的儿科患者，鼻腔给药负载舒必利的甘油osomal原位凝胶是口服治疗的一种有前途的替代方法。
