Ghazwani Mohammed, Vasudevan Rajalakshimi, Kandasamy Geetha, Manusri Naredla, Devanandan Praveen, Puvvada Ranadheer Chowdary, Veeramani Vinoth Prabhu, Paulsamy Premalatha, Venkatesan Krishnaraju, Chidmabaram Kumarappan, Dhurke Rajeshri
Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia.
Department of Pharmacology and Toxicology, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia.
Gels. 2023 Jun 2;9(6):457. doi: 10.3390/gels9060457.
The purpose of the present work was to develop nanoemulsion-based formulations of mirtazapine for intranasal delivery using a spray actuator to target the brain for treating depression. Research on the solubility of medications in different oils, surfactants, co-surfactants, and solvents has been done. Using pseudo-ternary phase diagrams, the various ratios of the surfactant and co-surfactant mix were computed. Thermotriggered nanoemulsion was formulated using different concentrations of poloxamer 407 (i.e., 15%, 15.5%, 16%, 16.5% up to 22%). Similarly, mucoadhesive nanoemulsion using 0.1% Carbopol and water-based plain nanoemulsions were also prepared for comparative assessment. The developed nanoemulsions were analyzed for physicochemical properties, i.e., physical appearance, pH, viscosity, and drug content. Drug-excipient incompatibility was determined by Fourier transform infrared spectral (FTIR) analysis and differential scanning calorimetry (DSC). In vitro drug diffusion studies were conducted for optimized formulations. Among the three formulations, RD1 showed the highest percentage of drug release. Ex vivo drug diffusion studies were conducted on freshly excised sheep nasal mucosa with Franz diffusion cell simulated nasal fluid (SNF) for all three formulations up to 6 h, and the thermotriggered nanoemulsion (RD1) showed 71.42% drug release with 42.64 nm particle size and a poly dispersity index of 0.354. The zeta potential was found to be -6.58. Based on the above data, it was concluded that thermotriggered nanoemulsion (RD1) has great potential to be used as an intranasal gel for treating depression in patients. It can offer great benefits by reducing dosing frequency and improving bioavailability of mirtazapine by direct nose-to-brain delivery.
本研究的目的是开发基于纳米乳剂的米氮平制剂，用于鼻腔给药，使用喷雾装置靶向大脑以治疗抑郁症。已开展了关于药物在不同油类、表面活性剂、助表面活性剂和溶剂中溶解度的研究。利用伪三元相图，计算了表面活性剂和助表面活性剂混合物的各种比例。使用不同浓度的泊洛沙姆407（即15%、15.5%、16%、16.5%直至22%）制备了热触发纳米乳剂。同样，还制备了使用0.1%卡波姆的粘膜粘附纳米乳剂和水基普通纳米乳剂用于比较评估。对所开发的纳米乳剂进行了物理化学性质分析，即外观、pH值、粘度和药物含量。通过傅里叶变换红外光谱（FTIR）分析和差示扫描量热法（DSC）确定药物-辅料不相容性。对优化后的制剂进行了体外药物扩散研究。在这三种制剂中，RD1显示出最高的药物释放百分比。对所有三种制剂在新鲜切除的绵羊鼻粘膜上使用Franz扩散池模拟鼻液（SNF）进行了长达6小时的离体药物扩散研究，热触发纳米乳剂（RD1）显示药物释放率为71.42%，粒径为42.64 nm，多分散指数为0.354。zeta电位为-6.58。基于上述数据，得出结论：热触发纳米乳剂（RD1）具有作为鼻腔凝胶用于治疗抑郁症患者的巨大潜力。它可以通过减少给药频率和通过直接鼻脑给药提高米氮平的生物利用度而带来巨大益处。
