Phenytoin: A promising non-antibiotic drug for the topical treatment of digital dermatitis in dairy cows

Background and Aim: Digital dermatitis (DD) is one of the most common causes of lameness in dairy cattle. It is seen in nearly all dairy herds across the world and has substantial welfare and economic implications. In this study, we aimed to investigate the efficacy of phenytoin sodium topical treatment on painful ulcerative stage of bovine digital dermatitis (BDD). Materials and Methods: In total, 45 Holstein-Friesian dairy cows with DD were randomly assigned to one of the three topical treatment trials (15 each): Saline solution (first treatment, negative control), chlortetracycline spray (second treatment, positive control), or phenytoin sodium powder (third treatment, positive control) (third treatment). On day 0 (pre-treatment) and on days 7, 14, 21, and 28 post-treatment, the response of DD-affected cows to the medications used was evaluated by measuring lesion depth and size, as well as the total clinical score (lameness, pain, and discomfort). Results: The cure rate in cows treated with phenytoin (86.66%) on day 28 was significantly improved compared to cows treated with either chlortetracycline (60%) or normal saline (6.66 %). Conclusion: Our findings highlight the superiority of phenytoin over the commonly used antibacterial agent, chlortetracycline, in the topical treatment of BDD, and subsequently suggest that phenytoin should be considered a suitable alternative treatment option for the treatment of BDD.

Nose to Brain Delivery of Phenytoin Sodium Loaded Nano Lipid Carriers: Formulation, Drug Release, Permeation and In Vivo Pharmacokinetic Studies

An acute epileptic seizure is a seizure emergency fatal condition that requires immediate medical attention. IV phenytoin sodium remains the second line therapeutic agent for the immediate treatment of status epilepticus. Phenytoin sodium formulated as nanolipid carriers (NLCs) seems to be promising as an intranasal delivery system for controlling acute seizures. Three different nanosized phenytoin sodium loaded NLCs (<50 nm, 50–100 nm and >100 nm) were prepared by melt emulsification and was further characterised. In vitro drug release studies showed immediate drug release from phenytoin sodium loaded NLCs of <50 nm size, which is highly essential for acute seizure control. The ex vivo permeation study indicated greater permeation from <50 nm sized NLC through the olfactory epithelium compared to thecontrol drug solution. Invivo pharmacokinetic studies revealed higher drug concentration in CSF/brain within 5 min upon intranasal administration of <50 nm sized phenytoin sodium NLCs than the control drug solution and marketed IV phenytoin sodium, indicating direct and rapid nose to brain drug transport through the olfactory epithelium. The study has shown that formulation strategies can enhance olfactory uptake, and phenytoin sodium NLCs of desired particle sizes (<50 nm) offer promising potential for nose to brain direct delivery of phenytoin sodium in treating acute epileptic seizures.