Design, characterization and evaluation of a novel dosage form of rebamipide as transdermal patches in rodent model of Parkinson’s disease
DOI:
https://doi.org/10.56782/pps.650Keywords:
Rebamipide, ransdermal patches, 6-Hydroxydopamine, Parkinson’s disease, GlucocerebrosidaseAbstract
Rebamipide at 80 mg/kg oral twice daily was previously found effective against a hemiparkinson’s model in rats. However, the high dose and frequency limit its advantages. Therefore, for the first time, a novel dosage form of rebamipide as transdermal patches was formulated, characterized and evaluated againt a rodent model of Parkinson’s disease. Four different transdermal formulations containing rebamipide were prepared using the solvent casting method (4 mg rebamipide/patch). Transdermal patches were observed to be uniform in terms of physicochemical characteristics. Rebamipide was administered through both the oral (80 mg/kg twice daily) and transdermal route (one patch daily) from Day-4 to Day-27 after unilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA) in male rats. Patches increased levels of dopamine, dopamine transporters, tyrosine hydroxylase, and glucocerebrosidase enzymatic activity and decreased α-synuclein pathology and motor deficits in 6-OHDA-infused rats. All the animal-related parameters include 6 rats per group, and behavioral studies include 12 rats per group. Repeated measures of two-way ANOVA was used for the analysis of behavioral parameters and ex vivo permeability. Remaining in vivo parameters, physicochemical characteristics (weight, thickness, folding endurance, surface pH, swelling, moisture loss and drug content uniformity) and skin irritation studies were analyzed by one-way ANOVA. Rebamipide concentration using HPLC was analyzed by an unpaired t test. The effects of rebamipide patches and oral groups against 6-OHDA toxicity were similar and the concentration of rebamipide in plasma and cerebrospinal fluid of both groups was also observed to be the same. These preclinical findings suggest that a low rebamipide dose administered once daily through a newly-prepared transdermal patch (4 mg drug/patch) showed similar potential as a high oral rebamipide dose (80 mg/kg) administered twice daily in rats against 6-OHDA toxicity. Further studies including detailed pharmacokinetic and mechanistic data are required in order to translate the information successfully from animal to clinical studies.
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