title: Formulation and stability of an extemporaneous 0.02% chlorhexidine digluconate ophthalmic solution.
abstract: OBJECTIVE
  Acanthamoeba keratitis is difficult to treat because Acanthamoeba cysts are resistant to the majority of antimicrobial agents. Despite the efficacy of 0.02% chlorhexidine in treating Acanthamoeba keratitis, a lack of data in the literature regarding the formulation's stability limits its clinical use. The objective of this study was to develop an optimal extemporaneous 0.02% chlorhexidine digluconate ophthalmic formulation for patients in need.
  
  
  METHODS
  With available active pharmaceutical ingredients, 0.02% chlorhexidine digluconate sample solutions were prepared by diluting with BSS Plus Solution or acetate buffer. Influences of the buffer, type of container, and temperature under daily-open condition were assessed based on the changes of pH values and chlorhexidine concentrations of the test samples weekly. To determine the beyond-use date, the optimal samples were stored at 2-8°C or room temperature, and analyzed at time 0 and at Week 1, Week 2, Week 3, Week 4, Week 5, Week 8, Week 12, and Week 24.
  
  
  RESULTS
  Despite chlorhexidine exhibiting better stability in acetate buffer than in BSS solution, its shelf-life was < 14 days when stored in a light-resistant low-density polyethylene container. The acetate-buffered 0.02% chlorhexidine digluconate solution stored in light-resistant high-density polyethylene eyedroppers did not exhibit significant changes in pH or strength at any time interval.
  
  
  CONCLUSIONS
  The acetate-buffered 0.02% chlorhexidine digluconate ophthalmic solution stored in light-resistant high-density polyethylene eyedroppers demonstrated excellent stability at 2-25°C for 6 months after being sealed and for 1 month after opening. This finding will enable us to prepare 0.02% chlorhexidine digluconate ophthalmic solutions based on a doctor's prescription.
authors.affiliation: Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Shu-Chiao
authors.initials: SC
authors.lastname: Lin
authors.affiliation: Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Pharmacy, Medical College, National Taiwan University, Taipei, Taiwan.
authors.forename: Chih-Fen
authors.initials: CF
authors.lastname: Huang
authors.affiliation: Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Pharmacy, Medical College, National Taiwan University, Taipei, Taiwan; School of Pharmacy, Medical College, National Taiwan University, Taipei, Taiwan.
authors.forename: Li-Jiuan
authors.initials: LJ
authors.lastname: Shen
authors.affiliation: Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Hsueh-Ju
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chia-Yu
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Pharmacy, Medical College, National Taiwan University, Taipei, Taiwan; School of Pharmacy, Medical College, National Taiwan University, Taipei, Taiwan. Electronic address: flwu@ntu.edu.tw.
authors.forename: Fe-Lin Lin
authors.initials: FL
authors.lastname: Wu
mesh_terms: D015823:Acanthamoeba Keratitis / Q000188:drug therapy; D002710:Chlorhexidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004339:Drug Compounding; D004355:Drug Stability; D006801:Humans; D009883:Ophthalmic Solutions / Q000592:standards*; D013997:Time Factors
chemical_list: D009883:Ophthalmic Solutions; C010882:chlorhexidine gluconate; D002710:Chlorhexidine
keywords: compatibility; dosage forms; drug compounding; infectious disease; ophthalmology; pharmaceutics