Stability of an extemporaneous oral liquid aprepitant formulation.
OBJECTIVE
Aprepitant is currently recommended for the prevention of acute antineoplastic-induced nausea and vomiting in adults receiving highly emetogenic therapy. The lack of an oral liquid dosage form is one barrier to its use in children. The purpose of this study was to develop a stable oral liquid formulation of aprepitant using the marketed aprepitant capsules.


METHODS
Aprepitant 20-mg/mL oral liquid was prepared from 125-mg capsule contents in Orablend(R). Twelve test samples were prepared: six packaged in amber glass and six in polyethylene terephthalate (PET) containers, three of each stored at either 23 degrees C or 4 degrees C. The physical characteristics of the oral aprepitant liquid stored in amber glass bottles were evaluated at the time of compounding and on days 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77, 84, and 91. The aprepitant content of three test solutions of each container type and storage temperature was determined using a stability-indicating assay at 5, 9, 14, 29, 48, 62, 73, and 111 days after compounding.


RESULTS
All samples stored in glass demonstrated suitable physical characteristics and those stored in either glass or PET retained more than 94.0% of the initial concentration. Based on the higher limit of the 95% confidence interval of the degradation rate, suspensions stored at 23 degrees C achieved 10% loss within 66 to 85 days, compared to greater than 100 days when stored at 4 degrees C.


CONCLUSIONS
The extemporaneous aprepitant oral suspension formulation described is physically and chemically stable for at least 90 days when refrigerated. The bioavailability of this formulation is unknown.
Dupuis
L Lee
LL
Division of Hematology/Oncology, Department of Pharmacy, Research Institute, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario M5G 1X8, Canada. lee.dupuis@sickkids.ca
Lingertat-Walsh
Karen
K
Walker
Scott E
SE
D000284:Administration, Oral; D000932:Antiemetics / Q000008:administration & dosage / Q000737:chemistry*; D000077608:Aprepitant; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002648:Child; D004339:Drug Compounding; D004349:Drug Packaging; D004355:Drug Stability; D004356:Drug Storage; D005898:Glass; D006801:Humans; D009025:Morpholines / Q000008:administration & dosage / Q000737:chemistry*; D019999:Pharmaceutical Solutions; D014677:Pharmaceutical Vehicles / Q000737:chemistry*; D011093:Polyethylene Terephthalates / Q000737:chemistry; D013696:Temperature; D013997:Time Factors
D000932:Antiemetics; D009025:Morpholines; D019999:Pharmaceutical Solutions; D014677:Pharmaceutical Vehicles; D011093:Polyethylene Terephthalates; D000077608:Aprepitant