The relations between ionic and non-ionic diffusion of sulfonamides across the rabbit cornea

Area of Science:

• Ophthalmology
• Pharmacology
• Medicinal Chemistry

Background:

• Carbonic anhydrase inhibitors (CAIs) are crucial in treating conditions like glaucoma.
• Understanding their ocular penetration is vital for effective drug delivery.
• The ionization state of acidic drugs significantly impacts their ability to cross biological membranes.

Purpose of the Study:

• To investigate the transcorneal permeability of five carbonic anhydrase inhibitors.
• To specifically analyze the passage of these acidic compounds in both ionized and nonionized forms.
• To determine how pH influences the ocular accumulation of CAIs.

Main Methods:

• Studied five carbonic anhydrase inhibitors with varying pKs (5.9–8.0) and partition coefficients.
• Applied solutions of varying pH to the cornea under steady-state conditions.
• Measured the passage rates of both ionized and nonionized forms to the anterior chamber.

Main Results:

• Ionized forms of CAIs exhibited surprisingly high corneal permeability, only 4-7 times lower than nonionized forms.
• Both ionized and nonionized forms contribute to corneal penetration.
• Increasing solution pH enhanced drug solubility and overall ocular accumulation rates.

Conclusions:

• Transcorneal permeability of carbonic anhydrase inhibitors is significant for both ionized and nonionized forms.
• Drug formulation pH is a critical factor in optimizing ocular drug delivery and efficacy.
• This study provides valuable insights for developing more effective topical ophthalmic medications.