| Diphenhydramine hydrochloride (DPH) is a classical H 1 receptor antagonist and reduces the effect of histamine. It is used in conditions like pruritus, urticaria and itching due to sunburn, poison ivy and bites and also to relieve coughing, and sneezing due to allergies. It is administered orally and topically.;Either of the preparations of diphenhydramine hydrochloride (DPH) require 3 or 4 administrations a day to inhibit effect of histamine by preventing from binding to its receptor. In general, Dosing regimens for DPH are based on plasma concentrations, then again, when therapeutical effect targeted the skin, a better understanding of the time course profile of DPH in skin helps design more effective dosage regimens. For this reason, this study addresses the evaluation of skin pharmacokinetics of commercially available topical formulations using the microdialysis technique to measure DPH concentration in dermis. Three female pathogen-free New Zealand albino rabbits received, according to a crossover design, predetermined amount of brand and generic products of cream and gel formulations. Skin dialysate samples were collected at 1-hour time intervals for six hours.;Skin samples were analyzed by a validated, reversed phase high performance liquid chromatography with UV detector. Mobile phase composition used was 50mM Phosphate buffer containing 7mM TEA at pH 3.0±0.05: Acetonitrile (60:40) for samples. In vivo microdialysis samples were injected directly onto HPLC system (Injection Volume 40μL). Calibration curves were linear in the range 10000 ng/mL to 50 ng/mL in lactated ringer's solution. The LLOQ was 50 ng/mL in dialysates.;DPH was never detectable in skin for cream formulation; in converse, DPH was detected in skin for brand and generic gels. The generic formulation appears to deliver statistically higher skin concentration than that of brand even though the difference may not be clinically significant. However, the clinically effective concentrations is unknown.;In conclusion this study shows that pharmacokinetics of DPH can be studied in the skin by microdialysis when it is delivered from gel formulations. |
