Development of prednisolone-containing eye drop formulations by cyclodextrin complexation and antimicrobial, mucoadhesive biopolymer

Drug Des Devel Ther. 2018 Aug 15;12:2529-2537. doi: 10.2147/DDDT.S165693. eCollection 2018.

Abstract

Purpose: The formulation of topical ophthalmic products with appropriate therapeutic effect and patient compliance is a major challenge. To increase the efficiency of the ocular delivery of the drug, the enhancement of water solubility and the contact time of the drug on the surface of the cornea are necessary. In this work, prednisolone (PR)-containing eye drops were formulated with antimicrobial, mucoadhesive biopolymer and PR-cyclodextrin inclusion complex. This approach can be used for the development of innovative ophthalmic formulations.

Materials and methods: After adjusting the optimal physiological parameters, the amount of the required cyclodextrin for the highest penetration of PR was determined by dialysis membrane diffusion study. The viscosity, surface tension and mucoadhesion of the eye drops were measured. The microbiological effectiveness of zinc-hyaluronate (ZnHA) was investigated by a standard method of the European Pharmacopoeia.

Results: In this case, no significant difference of surface tension was measured in products with different amounts of cyclodextrin. According to the results of the tensile test, ZnHA as a mucoadhesive biopolymer improves the mucoadhesion of ophthalmic products. The antimicrobial stability of formulations preserved by ZnHA meets requirement B of the European Pharmacopoeia.

Conclusion: It can be stated that the innovative PR-containing compositions are suitable for producing mucoadhesive, properly preserved aqueous ophthalmic solutions with increased bioavailability attributes.

Keywords: membrane diffusion; microbiological stability; ocular drug delivery; pharmaceutical formulation; zinc-hyaluronate.

MeSH terms

  • Adhesiveness
  • Administration, Ophthalmic
  • Anti-Infective Agents / administration & dosage
  • Anti-Infective Agents / chemistry*
  • Candida albicans / drug effects
  • Candida albicans / growth & development
  • Drug Carriers*
  • Drug Compounding
  • Drug Stability
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / chemistry*
  • Hyaluronic Acid / administration & dosage
  • Hyaluronic Acid / chemistry*
  • Ophthalmic Solutions
  • Organometallic Compounds / administration & dosage
  • Organometallic Compounds / chemistry*
  • Prednisolone / administration & dosage
  • Prednisolone / chemistry*
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / growth & development
  • Solubility
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / growth & development
  • Surface Tension
  • Viscosity
  • gamma-Cyclodextrins / chemistry*

Substances

  • Anti-Infective Agents
  • Drug Carriers
  • Glucocorticoids
  • Ophthalmic Solutions
  • Organometallic Compounds
  • gamma-Cyclodextrins
  • hydroxypropyl-gamma-cyclodextrin
  • zinc hyaluronate complex
  • Hyaluronic Acid
  • Prednisolone