Transcorneal permeation of diclofenac as a function of temperature from film formulation in presence of triethanolamine and benzalkonium chloride

• Permeation of diclofenac (DCP) ocular film carried out as a function of temperature.
• Improved permeation has been supported by decreased activation energy.
• Triethanolamine led to ion pair formation with DCP and resulted higher permeability.
• Benzalkonium broke the physiological diffusion barrier and favored the permeation.
• Film swelled by pronounced lachrymal fluid uptake and remained 6 h of application.

The objective of this report was to evaluate the transcorneal permeation of diclofenac potassium (DCP) as a function of temperature from hydroxypropyl methylcellulose (HPMC) matrix film containing triethanolamine (TEM) as plasticizer and benzalkonium chloride (BKC) as preservative. Activation energy (Ea), enthalpy (ΔH), entropy (ΔS) and free energy (ΔG) of permeation, diffusion and partition were evaluated to understand the underlying mechanism of permeation. Permeation improved with the presence of both the plasticizer and preservative compared to preservative alone. Further, increased amount of TEM in the film increased drug transport across the cornea. Decreased Ea value of the film supported the fact. Rise of temperature from 26 to 30, 34 and 40 °C increased permeation in all the films. Ocular residence of the film in vivo in the rabbit revealed that the film swelled by pronounced lachrymal fluid uptake and traces of hydrogel remained still at the end of 6 h of application. Absence of characteristic exothermic peak of the drug in the thermogram of film formulations indicated the molecular dispersion of drug in polymer matrix. Scanning electron microscopy indicated that the drug crystal size decreased with increasing concentration of TEM in presence of BKC due to effective wetting of drug particles by the polymer.

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