Rapid pain relief using transdermal film forming polymeric solution of ketorolac.

CONTEXT: Ketorolac is one of the most potent nonsteroidal anti-inflammatory drugs and is an attractive alternative to opioids for pain management. OBJECTIVE: Development and evaluation of transdermal ketorolac film forming polymeric solution. MATERIALS AND METHODS: Eudragits(®) RLPO, RSPO and E100 as well as polyvinyl pyrrolidone K30 dissolved in ethanol were used as film forming solutions. In vitro experiments were conducted to optimize formulation parameters. Different permeation enhancers were monitored for potentiality of enhancing drug permeation across excised pigskin. RESULTS: The use of 10% oleic acid, Lauroglycol(®) 90 or Azone(®) with 5% Eudragit(®) RSPO, showed the highest enhancement effect on ketorolac skin permeation and showed faster analgesic effect compared to the ketorolac tablet. The formula comprising 5% Eudragit(®) RSPO and 10% Lauroglycol(®) 90 showed the greatest pharmacodynamic effect and thus was subjected to pharmacokinetic studies. The pharmacodynamic and pharmacokinetic results didn't run paralleled to each other, as the ketorolac tablets showed higher plasma concentrations compared to the selected ketorolac transdermal formulation. This might be due to the induction of analgesia by the available ethanol in the transdermal preparation. CONCLUSION: Optimized transdermal ketorolac formulation showed marked ability to ensure fast and augmented analgesic effect that is an essential request in pain management.

Inclusion complexation of furosemide in cyclodextrins. Part 2: Implication on bioavailability.

The effect of inclusion complexation of furosemide in cyclodextrins (CyD) on the bioavailability of the drug was studied on normal human volunteers. The excretion rate of the drug was determined by HPLC for a period of 24 h. post dosing. Several pharmacokinetic parameters were calculated and statistically analyzed. viz., peak excretion rate, peak excretion time, half peak time, elimination rate constant, area under the excretion rate time-curve as well as the total amount of drug excreted. The obtained results show that on administration of furosemide in the form of an inclusion complex in CyDs particularly beta-CyD or its dimethyl derivative may improve its biological performance, taking into consideration that furosemide is characterized by a rapid onset and a short duration of action. Inclusion complexation of furosemide in CyDs leads to a more or less delay in its onset of action, a significant increase in its duration of action as well as significant augmentation in its overall biological availability.

Improvement of the biological performance of oral anticoagulant drugs. 1. Warfarin.

Coevaporates of warfarin sodium containing different weight fractions of polyvinylpyrrolidone (Kollidon s5 and 30) polymers of different molecular weights were prepared and their characterization, dissolution properties as well as their bioavailability in rabbits were assessed. UV and IR spectrophotometery revealed a sort of binding between the drug and polymers. Optimum binding tendency appears at polymer weight fractions of 0.7 and 0.5 for Kollidon 25 and Kollidon 30, respectively. Incorporation of the drug with PVP enhances its dissolution properties and improves its bioavailability. Of all the investigated warfarin/PVP systems, the coevaporate of warfarin with an equal weight fraction of Kollidon 30 was found to exhibit optimum biological properties beside highest dissolution rate.

Interaction of oral anticoagulants with methyl xanthines.

The interaction of warfarin and dicumarol with methyl xanthines was monitored. The results revealed formation of equimolar complexes with both caffeine and theophylline. The interaction is exothermic and complexation is thermodynamically unfavourable. The apparent solubility of dicumarol in water was found to increase linearly with increasing methyl xanthine concentration. The dissolution rate of the prepared complexes is higher than that of their respective physical mixtures or the respective drug per se. The implication of such interaction on the biological performance of the two anticoagulants was assessed in Albino rabbits. The results indicate that incorporation of dicumarol in form of a complex or even as a physical mixture with methyl xanthines does affect the biological performance of the drug to a marked extent.