Formulation of hydrophilic non-aqueous gel: drug stability in different solvents and rheological behavior of gel matrices

Pharm Res. 2008 Jan;25(1):207-17. doi: 10.1007/s11095-007-9457-3. Epub 2007 Oct 2.

Abstract

Purpose: This study was aimed at formulating a hydrophilic non-aqueous gel for topical delivery of the model moisture-sensitive drug, minocycline hydrochloride (MH).

Methods: Stability study of MH dissolved in water and various hydrophilic non-aqueous solvents was performed over a period of four months in order to select a suitable non-aqueous solvent for MH gel. To improve MH stability, the effect of different cation additives on MH stability in the selected solvent was investigated. Non-aqueous gel matrices were prepared from three different types of hydrophilic polymers in glycerin-propylene glycol mixture with Mg(2+) cation additive. Oscillatory shear rheometry was performed on the gel matrices using a cone-and-plate rheometer.

Results: MH stability was affected by the type of solvent employed and the duration of storage. Different cation additives affected the extent of MH stabilization through MH-cation complex formation. Rheological properties of the non-aqueous gel matrices were significantly affected by the type and concentration of polymer, and the vehicle ratios in the formulations.

Conclusions: MH stabilization could be achieved using the selected glycerin-propylene glycol mixture containing MgCl(2). Gel matrix formulated using this solvent system and 3%w/w N-vinylacetamide/sodium acrylate copolymer had demonstrated the most favorable rheological properties as a gel for topical application.

MeSH terms

  • Administration, Topical
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / chemistry*
  • Cations / chemistry
  • Chemistry, Pharmaceutical
  • Chromatography, High Pressure Liquid
  • Drug Delivery Systems
  • Drug Stability
  • Gels
  • Minocycline / administration & dosage*
  • Minocycline / chemistry*
  • Rheology
  • Solvents
  • Viscosity
  • Water / chemistry

Substances

  • Anti-Bacterial Agents
  • Cations
  • Gels
  • Solvents
  • Water
  • Minocycline