The development of a silicone vaginal ring with a prostaglandin analogue for potential use in the treatment of canine reproductive disorders

Pharm Dev Technol. 2019 Oct;24(8):1021-1031. doi: 10.1080/10837450.2019.1622565. Epub 2019 Jun 21.

Abstract

In veterinary medicine, vaginal rings (VRs) are rarely used. However, there are diseases of female dogs' reproductive system which represent a suitable possibility for their usage. An example of such a disease is canine pyometra which can be treated by lipophilic prostaglandin drugs, unfortunately with harmful side effects after systemic administration. The aim of the study was to prove that the matrix VR based on silicone and channel-forming substance can be successfully used as a carrier for a three-day delivery of prostaglandin E2 (PGE2). Based on an in-vitro release study, an optimum channel-forming substance and its concentration were selected. The results were implemented during the construction of VR from the medical grade silicone DDU-4840 with PGE2 (5 mg). Glucose anhydrous in the 30% concentration was chosen as the most functional channel-forming substance due to synergism of osmotic activity and solubility. The DDU-VR containing PGE2 and 30% of glucose anhydrous exhibited excellent mechanical characteristics and ensured 29% drug release through water-filled channels in first-order kinetic manner. This is eight times higher than a sample without glucose where molecular diffusion through the silicone matrix was dominating the release mechanism. Moreover, drug-free VRs were tested for mechanical resistance and the design of removal thread.

Keywords: Drug delivery; canine pyometra; channel-forming substance; prostaglandin; silicone; vaginal ring.

MeSH terms

  • Animals
  • Contraceptive Devices, Female
  • Diffusion
  • Dogs
  • Drug Liberation / drug effects
  • Female
  • Genitalia, Female / drug effects*
  • Glucose / chemistry
  • Kinetics
  • Prostaglandins / administration & dosage*
  • Prostaglandins / chemistry*
  • Reproduction / drug effects*
  • Silicones / chemistry*
  • Solubility / drug effects

Substances

  • Prostaglandins
  • Silicones
  • Glucose