Smail Shahla S, Ghareeb Mowafaq M, Omer Huner K, Al-Kinani Ali A, Alany Raid G
Drug Discovery, Delivery and Patient Care (DDDPC) Theme, Department of Pharmacy, Kingston University, Kingston upon Thames, London KT1 2EE, UK.
Department of Pharmaceutics, College of Pharmacy, Hawler Medical University, Kurdistan Region, Erbil 44001, Iraq.
Pharmaceutics. 2021 Mar 30;13(4):467. doi: 10.3390/pharmaceutics13040467.
Nanoemulsions (NE) are isotropic, dispersions of oil, water, surfactant(s) and cosurfactant(s). A range of components (11 surfactants, nine cosurfactants, and five oils) were investigated as potential excipients for preparation of ketorolac tromethamine (KT) ocular nanoemulsion. Diol cosurfactants were investigated for the effect of their carbon chain length and dielectric constant (DEC), Log , and HLB on saturation solubility of KT. Hen's Egg Test-ChorioAllantoic Membrane (HET-CAM) assay was used to evaluate conjunctival irritation of selected excipients. Of the investigated surfactants, Tween 60 achieved the highest KT solubility (9.89 ± 0.17 mg/mL), followed by Cremophor RH 40 (9.00 ± 0.21 mg/mL); amongst cosurfactants of interest ethylene glycol yielded the highest KT solubility (36.84 ± 0.40 mg/mL), followed by propylene glycol (26.23 ± 0.82 mg/mL). The solubility of KT in cosurfactants was affected by four molecular descriptors: carbon chain length, DEC, log and HLB. KT solubility was directly proportional to DEC and the HLB yet, inversely proportional to carbon chain length and log . All surfactants, except Labrasol ALF, were non-irritant. The majority of cosurfactants were slightly irritant, butylene glycol was a moderate irritant, pentylene and hexylene glycols were strong irritants. These findings will inform experiments aimed at developing NE formulations for ocular administration of KT.
纳米乳剂（NE）是油、水、表面活性剂和助表面活性剂的各向同性分散体。研究了一系列成分（11种表面活性剂、9种助表面活性剂和5种油）作为制备酮咯酸氨丁三醇（KT）眼部纳米乳剂的潜在辅料。研究了二醇类助表面活性剂的碳链长度、介电常数（DEC）、Log 以及亲水亲油平衡值（HLB）对KT饱和溶解度的影响。采用鸡胚绒毛尿囊膜（HET-CAM）试验评估所选辅料的结膜刺激性。在所研究的表面活性剂中，吐温60的KT溶解度最高（9.89±0.17mg/mL），其次是聚氧乙烯蓖麻油RH40（9.00±0.21mg/mL）；在所关注的助表面活性剂中，乙二醇的KT溶解度最高（36.84±0.40mg/mL），其次是丙二醇（26.23±0.82mg/mL）。KT在助表面活性剂中的溶解度受四个分子描述符的影响：碳链长度、DEC、log 和HLB。KT溶解度与DEC和亲水亲油平衡值成正比，但与碳链长度和log 成反比。除了Labrasol ALF外，所有表面活性剂均无刺激性。大多数助表面活性剂有轻微刺激性，丁二醇有中度刺激性，戊二醇和己二醇有强烈刺激性。这些研究结果将为旨在开发用于眼部给药的KT纳米乳剂配方的实验提供参考。
