Department of Chemical Engineering, University of Florida, Gainesville, Florida, 32611-6005, USA.
Pharm Res. 2017 Dec;34(12):2862-2872. doi: 10.1007/s11095-017-2270-8. Epub 2017 Oct 24.
About 70% of eye drops contain benzalkonium chloride (BAK) to maintain sterility. BAK is an effective preservative but it can cause irritation and toxicity. We propose to mitigate ocular toxicity without compromising sterility by incorporating a filter into an eye drop bottle to selectively remove BAK during the process of drop instillation.
The filter is a packed bed of particles made from poly(2-hydroxyethyl methacrylate) (pHEMA), which is a common ophthalmic material. We showed that pHEMA particle prepared by using ethoxylated trimethylolpropane triacrylate as crosslinker can be incorporated into a modified eyedrop bottle tip to selectively remove the preservative as the formulation is squeezed out of the bottle. Hydraulic permeability of the plug is measured to determine the resistance to eye drop squeezing, and % removal of BAK and drugs are determined.
The modified tip has a hydraulic permeability of about 2 Darcy, which allows eyedrops formulations to flow through without excessive resistance. The tip is designed such that the patients can create an eyedrop of solution of 1-10 cP viscosity in 4 s with a nominal pressure. During this short contact time, the packed particles removed nearly 100% of benzalkonium chloride (BAK) from a 15 mL, 0.012% BAK solution but have only minimal impact on the concentration of contained active components.
Our novel design can eliminate the preservative induced toxicity from eye drops thereby impacting hundreds of millions of patients with chronic ophthalmic diseases like glaucoma and dry eyes.
大约 70%的眼药水含有苯扎氯铵 (BAK) 以保持无菌状态。BAK 是一种有效的防腐剂，但它会引起刺激和毒性。我们建议通过在滴眼瓶中加入过滤器来选择性地去除 BAK，从而在滴眼过程中减轻眼毒性，同时不影响无菌状态。
过滤器是由聚(2-羟乙基甲基丙烯酸酯) (pHEMA) 制成的填充颗粒床，这是一种常见的眼科材料。我们表明，使用乙氧基化三羟甲基丙烷三丙烯酸酯作为交联剂制备的 pHEMA 颗粒可以被纳入改良滴眼瓶的尖端，以在制剂从瓶中挤出时选择性地去除防腐剂。通过测量堵塞物的水力渗透率来确定对滴眼剂挤压的阻力，以及 BAK 和药物的去除百分比。
改良的尖端具有约 2 达西的水力渗透率，允许滴眼剂配方无过度阻力地流过。该尖端的设计使得患者可以在 4 秒内用名义压力产生 1-10 cP 粘度的滴眼剂溶液。在这段短的接触时间内，填充颗粒从 15 毫升 0.012% BAK 溶液中去除了近 100%的苯扎氯铵 (BAK)，但对所含活性成分的浓度只有很小的影响。
我们的新设计可以消除眼药水引起的防腐剂毒性，从而影响数以亿计的患有慢性眼病（如青光眼和干眼症）的患者。
