title: Aluminum elution and precipitation in glass vials: effect of pH and buffer species.
abstract: Inorganic extractables from glass vials may cause particle formation in the drug solution. In this study, the ability of eluting Al ion from borosilicate glass vials, and tendencies of precipitation containing Al were investigated using various pHs of phosphate, citrate, acetate and histidine buffer. Through heating, all of the buffers showed that Si and Al were eluted from glass vials in ratios almost the same as the composition of borosilicate glass, and the amounts of Al and Si from various buffer solutions at pH 7 were in the following order: citrate > phosphate > acetate > histidine. In addition, during storage after heating, the Al concentration at certain pHs of phosphate and acetate buffer solution decreased, suggesting the formation of particles containing Al. In citrate buffer, Al did not decrease in spite of the high elution amount. Considering that the solubility profile of aluminum oxide and the Al eluting profile of borosilicate glass were different, it is speculated that Al ion may be forced to leach into the buffer solution according to Si elution on the surface of glass vials. When Al ions were added to the buffer solutions, phosphate, acetate and histidine buffer showed a decrease of Al concentration during storage at a neutral range of pHs, indicating the formation of particles containing Al. In conclusion, it is suggested that phosphate buffer solution has higher possibility of forming particles containing Al than other buffer solutions.
authors.affiliation: Formulation Technology Research Laboratories, Daiichi Sankyo Co., Ltd. , Hiratsuka, Kanagawa , Japan and.
authors.forename: Toru
authors.initials: T
authors.lastname: Ogawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Miyajima
authors.forename: Naoki
authors.initials: N
authors.lastname: Wakiyama
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Terada
mesh_terms: D000535:Aluminum; D000537:Aluminum Oxide; D002021:Buffers; D011232:Chemical Precipitation; D002626:Chemistry, Pharmaceutical; D004349:Drug Packaging; D005898:Glass; D006358:Hot Temperature; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007267:Injections; D012822:Silicon Dioxide; D012995:Solubility; D012996:Solutions
chemical_list: D002021:Buffers; D012996:Solutions; D012822:Silicon Dioxide; D000535:Aluminum; D000537:Aluminum Oxide
keywords: Acetate buffer; aluminum; borosilicate glass; citrate buffer; extractables; histidine buffer; phosphate buffer