Bladder tissue permeability and transport modelling of intravesical alum, lidocaine hydrochloride, methylprednisolone hemisuccinate and mitomycin C

Int J Pharm. 2014 Apr 10;464(1-2):91-103. doi: 10.1016/j.ijpharm.2014.01.021. Epub 2014 Jan 22.

Abstract

The aims of this study were to assess the tissue permeability of the bladder and to characterize the transport of four drugs displaying different physico-chemical properties and commonly used in intravesical delivery, through porcine bladder. The transport of aluminium through porcine bladder was assessed by using a vertical static diffusion cell. Lidocaine hydrochloride, methylprednisolone hemisuccinate and mitomycin C were tested by using three different experimental setups, including vertical static diffusion cell, microdialyseur and lab-patented device. Penetration results on different experimental setups were homogenous suggesting dependency on physico-chemical characteristics of drug and subsequent interaction with bladder wall structure. Oppositely, permeation varied consistently with experimental setup characteristics (i.e., permeation surface, receptor fluid volume and hydrodynamic). Mathematical modelling of drug transport through bladder wall is proposed considering scarce literature on this route of administration. Practical outcome of this study could drive compounding optimization towards improvement of safety and efficacy in patient undergoing intravesical administration.

Keywords: Bladder; Fickian model; Intravesical drug delivery; Permeability.

MeSH terms

  • Administration, Intravesical
  • Alum Compounds / administration & dosage
  • Alum Compounds / metabolism*
  • Animals
  • Biological Transport / drug effects
  • Biological Transport / physiology
  • Lidocaine / administration & dosage
  • Lidocaine / metabolism*
  • Mitomycin / administration & dosage
  • Mitomycin / metabolism*
  • Organ Culture Techniques
  • Permeability / drug effects
  • Swine
  • Urinary Bladder / drug effects
  • Urinary Bladder / metabolism*

Substances

  • Alum Compounds
  • aluminum sulfate
  • Mitomycin
  • Lidocaine