Identification of subvisible barium sulfate crystals in parenteral solutions

Boddapati, S. N. Murthy; Butler, L.David; Im, Sophann; Deluca, Patric P.

doi:10.1002/jps.2600690540

Cited by 14 publications

(6 citation statements)

References 2 publications

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“…Boddapati et al 13) reported the phenomenon that barium (Ba) from borosilicate glass and sulfate ions from a drug formulation interacted, resulting in barium sulfate (BaSO 4 ) generation. The formation of Al-phosphate complexes proposed in this study is considered to be a similar phenomenon to the barium sulfate generation process.…”

Section: Resultsmentioning

confidence: 99%

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Effects of Phosphate Buffer in Parenteral Drugs on Particle Formation from Glass Vials

Ogawa

Miyajima

Wakiyama

et al. 2013

CHEMICAL & PHARMACEUTICAL BULLETIN

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The characteristics of inorganic particles generated in glass vials filled with phosphate buffer solutions were investigated. During storage, particles were visually detected in the phosphate buffer solution in particular glass vials which pass compendial tests of containers for injectable drugs. These particles were considered to be different from ordinal glass delamination, which has been reported in a number of papers because the particles were mainly composed of Al, P and O, but not Si. The formation of the particles accelerated at higher storage temperatures. Among the surface treatments tested for the glass vials, sulfur treatment showed a protective effect on the particle formation in the vials, whereas the SiO 2 coating did not have any protective effects. It was found that the elution ratio of Al and Si in the solution stored in the glass vials after the heating was similar to the ratio of Al and Si in borosilicate glass. However, the Al concentration decreased during storage (5°C, 6 months), and consequently, particle formation was observed in the solution. Adding citrate, which is a chelating agent for Al, effectively suppressed the particle formation in the heated solution. When 50 ppb and higher concentrations of Al ion were added to the phosphate buffer solution, the formation of white particles containing Al, P and O was detected. It is suggested that a phosphate buffer solution in a borosilicate glass vial has the ability to form particles due to interactions with the Al that is eluted from the glass during storage.Key words aluminum; borosilicate glass; tubing vial; aluminum phosphate complex The primary packaging system for a sterile drug product should provide adequate protection against any contamination from the external environment, and this protection should be assured during the entire shelf life of the product. In contrast, particularly for liquid, injectable drugs, components of the drugs are always in contact with the surface of the packaging component during storage. Therefore, during the course of formulation development of injectable drugs, it is essential to evaluate the physicochemical compatibility between the drug formulation and the packaging components to select appropriate primary packaging systems. 1,2) Among the packaging materials that are compatible with injectable drug solutions, glass containers, such as vials or ampoules, have been widely chosen and used. For parenteral drug products, borosilicate glasses (Type I) composed principally of silicon dioxide and boric oxides and soda-lime glasses composed of relatively high levels of sodium oxide and calcium oxide are used. Borosilicate glasses in particular are known to have a good chemical durability and are used commonly in the pharmaceutical industry as the primary container. However, these glass containers, even when made from borosilicate glasses, will unavoidably suffer some undesirable events from being in contact with the drug solutions in longterm storage. In certain cases, insoluble particle formation occurs in g...

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Section: Resultsmentioning

confidence: 99%

“…However, there are some reports of particle formation involving a mechanism other than delamination. 13) In addition to delamination, it is necessary to address the other particles that are formed as the result of interactions between the inner surface of the glass and the drug products.…”

mentioning

confidence: 99%

Effects of Phosphate Buffer in Parenteral Drugs on Particle Formation from Glass Vials

Ogawa

Miyajima

Wakiyama

et al. 2013

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…It was thought that this might be barium sulfate or calcium sulfate leached from the glass vessel. It is a known problem in the pharmaceutical industry with vials of solutions for injection . Again, the amounts were too small to identify but enough to interfere with the measurements.…”

Section: Discussionmentioning

confidence: 99%

Design of Experiment Study of the Seeding of Magnesium Sulfate Solutions

Coles

Robinson

Davesne

et al. 2022

Crystal Growth & Design

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“…There are some researchers [11][12][13] who reported the precipitation of the drug solution and there are also researchers 14,15 who discussed extractables from the glass; however, there is less comprehensive information on the effect of the interaction between the drug solution and the extractables.…”

Section: Introductionmentioning

confidence: 97%

Aluminum elution and precipitation in glass vials: effect of pH and buffer species

Ogawa¹,

Miyajima²,

Wakiyama³

et al. 2013

Drug Development and Industrial Pharmacy

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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.

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Identification of subvisible barium sulfate crystals in parenteral solutions

Cited by 14 publications

References 2 publications

Effects of Phosphate Buffer in Parenteral Drugs on Particle Formation from Glass Vials

Effects of Phosphate Buffer in Parenteral Drugs on Particle Formation from Glass Vials

Design of Experiment Study of the Seeding of Magnesium Sulfate Solutions

Aluminum elution and precipitation in glass vials: effect of pH and buffer species

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