The present study was undertaken to prepare and evaluate monolithic drug-inadhesive type transdermal patches of melatonin containing penetration enhancers such as fatty alcohols, fatty acids, and terpenes. The patches were prepared using Eudragit E 100 as the adhesive polymer. The release profile of melatonin from control as well as enhancer-containing patches showed an initial burst of melatonin release for up to 4 hours and then a plateau after 8 hours. The release profiles of melatonin from patches containing various enhancers were similar to the control patch. However, the addition of enhancers in the patch increased the permeation of melatonin through hairless rat skin. The flux values of patches containing octanol, nonanoic acid, and myristic acid were higher than the control patch (no enhancer), but the differences were not statistically significant (P>0.05). Decanol, myristyl alcohol, and undecanoic acid at 5% concentrations showed significantly higher flux values through hairless rat skin (enhancement ratios 1.7, 1.5, and 1.6 for decanol, myristyl alcohol, and undecanoic acid, respectively) (P<0.05). Menthol and limonene at 5% w/w showed maximum permeation of melatonin among all enhancers studied (enhancement ratios=2.1 and 2.0 for menthol and limonene, respectively) (P<0.001). In general, there was about 4-6 hours of lag time observed before a steady state flux of melatonin was achieved. Though the flux of melatonin observed in the present study is 5-10 times higher than the required delivery rate in humans, it must be noted that the present study was performed using hairless rat skin, which is generally more permeable compared to human skin. Further studies using human skin would prove the usefulness of these patches.

BackgroundLower urinary tract infections are common in dogs, and Escherichia coli is the most common bacterial pathogen isolated. The literature has conflicting evidence regarding the inhibitory effects of urine concentration and pH on E. coli growth.Hypothesis/ObjectivesTo determine the effect of different pH and urine concentrations on E. coli growth in vitro.AnimalsVoided urine samples from 10 apparently healthy spayed female dogs were used.MethodsA matrix of 9 urine specific gravity (USG; 1.010, 1.020, and 1.030) and pH (5.5, 7.0, and 8.5) combinations was prepared by diluting and titrating filtered voided urine samples. Three E. coli isolates were obtained from urine of female dogs with signs of lower urinary tract infection and cultured at different urine pH and USG combinations in wells of a microtiter plate. The number of E. coli colony‐forming units (CFU) per mL of urine was calculated after aerobic incubation of the urine at 37°C for 18 hours, and statistically compared.ResultsSignificant differences were identified in the mean log CFU/mL among different combinations of pH and USG. The lowest log CFU/mL were observed in alkaline concentrated urine (pH 8.5 and USG 1.030).Conclusions and Clinical Importance Escherichia coli in vitro growth was higher in neutral to acidic and diluted urine compared to alkaline and concentrated urine. The impact of non‐alkalizing diluting diets on the incidence of E. coli lower urinary tract infections should be further explored.

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