Sharma Charu, Biswas Nihar R, Ojha Shreesh, Velpandian Thirumurthy
Department of Ocular Pharmacology and Pharmacy, All India Institute of Medical Sciences, New Delhi, India; Department of Internal Medicine, United Arab Emirates University, Al Ain, UAE.
Department of Ocular Pharmacology and Pharmacy, All India Institute of Medical Sciences, New Delhi, India.
Drug Des Devel Ther. 2016 Feb 22;10:811-23. doi: 10.2147/DDDT.S95870. eCollection 2016.
Corneal permeability of drugs is an important factor used to assess the efficacy of topical preparations. Transcorneal penetration of drugs from aqueous formulation is governed by various physiological, physiochemical, and formulation factors. In the present study, we investigated the effect of formulation factors like concentration, pH, and volume of instillation across the cornea using cassette dosing technique for ophthalmic fluoroquinolones (FQs).
Sterile cocktail formulations were prepared using four congeneric ophthalmic FQs (ofloxacin, sparfloxacin, pefloxacin mesylate, and gatifloxacin) at concentrations of 0.025%, 0.5%, and 0.1%. Each formulation was adjusted to different pH ranges (4.5, 7.0, and 8.0) and assessed for transcorneal penetration in vivo in rabbit's cornea (n=4 eyes) at three different volumes (12.5, 25, and 50 μL). Aqueous humor was aspirated through paracentesis after applying local anesthesia at 0, 5, 15, 30, 60, 120, and 240 minutes postdosing. The biosamples collected from a total of 27 groups were analyzed using liquid chromatography-tandem mass spectroscopy to determine transcorneal permeability of all four FQs individually.
Increase in concentration showed an increase in penetration up to 0.05%; thereafter, the effect of concentration was found to be dependent on volume of instillation as we observed a decrease in transcorneal penetration. The highest transcorneal penetration of all FQs was observed at pH 7.0 at concentration 0.05% followed by 0.025% at pH 4.5. Lastly, increasing the volume of instillation from 12.5 to 50 μL showed a significant fall in transcorneal penetration.
The study concludes that formulation factors showed discernible effect on transcorneal permeation; therefore, due emphasis should be given on drug development and design of ophthalmic formulation.
药物的角膜通透性是评估局部制剂疗效的一个重要因素。药物从水性制剂中的角膜渗透受多种生理、物理化学和制剂因素的影响。在本研究中，我们使用眼科氟喹诺酮类药物（FQs）的卡式给药技术，研究了浓度、pH值和滴注体积等制剂因素对角膜渗透的影响。
使用四种同类眼科FQs（氧氟沙星、司帕沙星、甲磺酸培氟沙星和加替沙星）制备无菌混合制剂，浓度分别为0.025%、0.5%和0.1%。每种制剂调节至不同的pH范围（4.5、7.0和8.0），并在兔角膜（n = 4只眼）体内以三种不同体积（12.5、25和50 μL）评估角膜渗透情况。给药后0、5、15、30、60、120和240分钟，在局部麻醉后通过前房穿刺抽取房水。使用液相色谱 - 串联质谱法分析从总共27组收集的生物样品，以分别测定所有四种FQs的角膜通透性。
浓度增加至0.05%时，渗透率增加；此后，发现浓度的影响取决于滴注体积，因为我们观察到角膜渗透降低。所有FQs在pH 7.0、浓度0.05%时角膜渗透率最高，其次是pH 4.5、浓度0.025%时。最后，将滴注体积从12.5 μL增加到50 μL时，角膜渗透率显著下降。
该研究得出结论，制剂因素对角膜渗透有明显影响；因此，在眼科制剂的药物开发和设计中应给予充分重视。
