Development of doxycycline hyclate suppositories and pharmacokinetic study in rabbits

Eur J Pharm Sci. 2020 Jan 15:142:105141. doi: 10.1016/j.ejps.2019.105141. Epub 2019 Nov 6.

Abstract

Doxycycline hiclate is a broad spectrum antibiotic widely used in human and veterinary medicine. The inability to perform the parenteral administration of drugs and the lack of oral preparations can be mentioned as difficulties in the treatment of animals in the domestic environment. In this scenario, the aim of this study was to investigate the bioavailability of the drug by rectal route, to propose a potential suppository formulation containing 25 mg of doxycycline as an alternative to the available injectable formulations. Hydrophilic and lipophilic suppositories were prepared, in polyethylene glycol (S-PEG) or cocoa butter (S-CBT), respectively. The suppositories were prepared and evaluated concerning visual characteristics, content, average weight, melting range, content uniformity and in vitro release. A stability study was performed and the two most stable formulations were submitted to a pharmacokinetic study in rabbits. The bioavailability of the suppositories was compared to the data of the intravenous (i.v.) formulation. PEG suppository showed 49.13% bioavailability and CBT 51.43% with Cmax equal to 2.06 ± 2.96 µg.mL-1 and 1.54 ± 0.28 µg.mL-1, respectively. The data obtained suggest that rectal administration may become another method of administration of doxycycline in the treatment of bacterial infections.

Keywords: Doxycycline; Pharmaceutical development; Pharmacokinetics; Rectal; Suppository; Veterinary.

MeSH terms

  • Administration, Rectal
  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacokinetics
  • Bacterial Infections / drug therapy
  • Biological Availability
  • Chemistry, Pharmaceutical / methods
  • Doxycycline / administration & dosage
  • Doxycycline / pharmacokinetics*
  • Male
  • Polyethylene Glycols / chemistry
  • Rabbits

Substances

  • Anti-Bacterial Agents
  • Polyethylene Glycols
  • Doxycycline