[go: up one dir, main page]
More Web Proxy on the site http://driver.im/

Terbutaline transdermal delivery: preformulation studies and limitations of in-vitro predictive parameters

J Pharm Pharmacol. 1996 Nov;48(11):1138-42. doi: 10.1111/j.2042-7158.1996.tb03909.x.

Abstract

A transdermal dosage form of terbutaline may be useful to prevent nocturnal wheezing by providing prolonged duration of action. It will also improve patient compliance and bioavailability. Controlled input of the drug would be an additional advantage as this will reduce the intersubject variability. Preformulation studies were conducted to determine the feasibility of a transdermal dosage form of terbutaline. The drug solubility in propylene glycol was 6.3 mg mL-1. The apparent partition coefficient (n-octanol/ deionized-water, pH 6.5) of terbutaline was 0.03. A pH-partition coefficient (octanol/buffer) profile indicated that the partition coefficient values were 0.02, 0.05 and 0.4 in buffers of pH 3, 7.4 and 9, respectively. The required drug flux through the human skin to attain therapeutic concentrations in the blood was calculated to be 3.3 micrograms cm-2 h-1 for a 10-cm2 transdermal delivery system. Rabbit, guinea-pig and human skin was tested as the penetration barrier using modified Franz diffusion cells. Terbutaline flux values through the rabbit and guinea-pig skin were 8.3 and 7.7 micrograms cm-2 h-1, respectively. The flux through human full-thickness skin and human epidermis were 0.6 and 3.6 micrograms cm-2 h-1. Azone (3% w/v), a skin penetration enhancer, significantly increased the drug flux through all the membranes tested. Based on these studies, transdermal delivery of terbutaline appears to be promising.

MeSH terms

  • Administration, Cutaneous
  • Aged
  • Animals
  • Azepines / pharmacokinetics*
  • Azepines / pharmacology
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / pharmacokinetics*
  • Dose-Response Relationship, Drug
  • Drug Carriers
  • Guinea Pigs
  • Humans
  • In Vitro Techniques
  • Male
  • Middle Aged
  • Permeability
  • Rabbits
  • Skin Absorption*
  • Terbutaline / administration & dosage
  • Terbutaline / pharmacokinetics*
  • Tissue Distribution

Substances

  • Azepines
  • Bronchodilator Agents
  • Drug Carriers
  • laurocapram
  • Terbutaline