Stability of frozen 1% voriconazole ophthalmic solution.
OBJECTIVE
The physicochemical stability of frozen 1% voriconazole ophthalmic solution was evaluated.


METHODS
Multiple batches of voriconazole 10-mg/mL eye drops were aseptically prepared in a laminar-airflow cabinet. One batch was analyzed immediately after preparation, and the rest were stored at -20 °C and analyzed using high-performance liquid chromatography at 30, 60, and 90 days to test their physicochemical stability and sterility. All samples were analyzed in triplicate. Additional analyses were performed to determine the solution's in vitro activity once thawed. The sterility of the 1% voriconazole solution was evaluated using blood-agar media and thioglycollate broth. Samples were incubated for 14 days and checked daily for signs of growth. Stability was defined as the absence of particles, color variation, or changes in pH and a remaining antifungal concentration of 90-110% of the initial concentration.


RESULTS
All solutions remained clear and colorless throughout the study, and no precipitation or turbidity was observed in any of the batches, regardless of solution temperature. The pH and osmolarity of all batches remained essentially unchanged during storage at -20 °C and after thawing. No significant differences in concentration were observed during the storage at -20 or 5 °C. The voriconazole concentration remained within 10% of the initial concentration during the 90-day period of storage at -20 °C. The percentage of recovery was also optimal after thawing.


CONCLUSIONS
Voriconazole 1% solution prepared for ophthalmic use was stable and retained antifungal activity when stored at -20 °C for 90 days. After thawing, this extemporaneously prepared formulation was stable at 5 °C for 14 days.
Patricia Amorós-Reboredo, Pharm.D., is Resident; and Carla Bastida-Fernandez, Pharm.D., is Resident, Pharmacy Service, Hospital Clinic of Barcelona, Barcelona, Spain. Laura Guerrero-Molina, Ph.D., is Postdoctoral Researcher, Research Laboratory CELLEX, Hospital Clinic Barcelona, and Postdoctoral Researcher, Institut D'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), CIBER de Enfermedades Respiratorias (CIBERES), University of Barcelona, Barcelona. Dolors Soy-Muner, Pharm.D., Ph.D., is Senior Consultant, Pharmacy Service, Research Laboratory CELLEX, Hospital Clinic of Barcelona, and Associate Professor, Pharmacy School, IDIBAPS, CIBERES, University of Barcelona. Carmen López-Cabezas, Pharm.D., is Hospital Pharmacist, Pharmacy Service, Hospital Clinic of Barcelona. The authors indicate that Drs. Amorós-Reboredo and Bastida-Fernandez contributed equally to this work. pamoros1@clinic.ub.es.
Patricia
P
Amorós-Reboredo
Patricia Amorós-Reboredo, Pharm.D., is Resident; and Carla Bastida-Fernandez, Pharm.D., is Resident, Pharmacy Service, Hospital Clinic of Barcelona, Barcelona, Spain. Laura Guerrero-Molina, Ph.D., is Postdoctoral Researcher, Research Laboratory CELLEX, Hospital Clinic Barcelona, and Postdoctoral Researcher, Institut D'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), CIBER de Enfermedades Respiratorias (CIBERES), University of Barcelona, Barcelona. Dolors Soy-Muner, Pharm.D., Ph.D., is Senior Consultant, Pharmacy Service, Research Laboratory CELLEX, Hospital Clinic of Barcelona, and Associate Professor, Pharmacy School, IDIBAPS, CIBERES, University of Barcelona. Carmen López-Cabezas, Pharm.D., is Hospital Pharmacist, Pharmacy Service, Hospital Clinic of Barcelona. The authors indicate that Drs. Amorós-Reboredo and Bastida-Fernandez contributed equally to this work.
Carla
C
Bastida-Fernandez
Patricia Amorós-Reboredo, Pharm.D., is Resident; and Carla Bastida-Fernandez, Pharm.D., is Resident, Pharmacy Service, Hospital Clinic of Barcelona, Barcelona, Spain. Laura Guerrero-Molina, Ph.D., is Postdoctoral Researcher, Research Laboratory CELLEX, Hospital Clinic Barcelona, and Postdoctoral Researcher, Institut D'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), CIBER de Enfermedades Respiratorias (CIBERES), University of Barcelona, Barcelona. Dolors Soy-Muner, Pharm.D., Ph.D., is Senior Consultant, Pharmacy Service, Research Laboratory CELLEX, Hospital Clinic of Barcelona, and Associate Professor, Pharmacy School, IDIBAPS, CIBERES, University of Barcelona. Carmen López-Cabezas, Pharm.D., is Hospital Pharmacist, Pharmacy Service, Hospital Clinic of Barcelona. The authors indicate that Drs. Amorós-Reboredo and Bastida-Fernandez contributed equally to this work.
Laura
L
Guerrero-Molina
Patricia Amorós-Reboredo, Pharm.D., is Resident; and Carla Bastida-Fernandez, Pharm.D., is Resident, Pharmacy Service, Hospital Clinic of Barcelona, Barcelona, Spain. Laura Guerrero-Molina, Ph.D., is Postdoctoral Researcher, Research Laboratory CELLEX, Hospital Clinic Barcelona, and Postdoctoral Researcher, Institut D'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), CIBER de Enfermedades Respiratorias (CIBERES), University of Barcelona, Barcelona. Dolors Soy-Muner, Pharm.D., Ph.D., is Senior Consultant, Pharmacy Service, Research Laboratory CELLEX, Hospital Clinic of Barcelona, and Associate Professor, Pharmacy School, IDIBAPS, CIBERES, University of Barcelona. Carmen López-Cabezas, Pharm.D., is Hospital Pharmacist, Pharmacy Service, Hospital Clinic of Barcelona. The authors indicate that Drs. Amorós-Reboredo and Bastida-Fernandez contributed equally to this work.
Dolors
D
Soy-Muner
Patricia Amorós-Reboredo, Pharm.D., is Resident; and Carla Bastida-Fernandez, Pharm.D., is Resident, Pharmacy Service, Hospital Clinic of Barcelona, Barcelona, Spain. Laura Guerrero-Molina, Ph.D., is Postdoctoral Researcher, Research Laboratory CELLEX, Hospital Clinic Barcelona, and Postdoctoral Researcher, Institut D'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), CIBER de Enfermedades Respiratorias (CIBERES), University of Barcelona, Barcelona. Dolors Soy-Muner, Pharm.D., Ph.D., is Senior Consultant, Pharmacy Service, Research Laboratory CELLEX, Hospital Clinic of Barcelona, and Associate Professor, Pharmacy School, IDIBAPS, CIBERES, University of Barcelona. Carmen López-Cabezas, Pharm.D., is Hospital Pharmacist, Pharmacy Service, Hospital Clinic of Barcelona. The authors indicate that Drs. Amorós-Reboredo and Bastida-Fernandez contributed equally to this work.
Carmen
C
López-Cabezas
D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D004356:Drug Storage; D005615:Freezing; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009883:Ophthalmic Solutions; D013696:Temperature; D013997:Time Factors; D065819:Voriconazole / Q000737:chemistry* / Q000494:pharmacology
D000935:Antifungal Agents; D009883:Ophthalmic Solutions; D065819:Voriconazole