Glass Vials for Small Volume Parenterals: Influence of Drug and Manufacturing Processes on Glass Delamination

Ennis, Richard D.; Pritchard, Ray; Nakamura, Carey; Coulon, Michael; Yang, Taiyin; Visor, Gary C.; Lee, William A.

doi:10.1081/pdt-100002248

Cited by 66 publications

(60 citation statements)

References 6 publications

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“…10,11) However, the particles detected in this study mainly contained Al and P, suggesting that these particles were different from the ordinal delaminated particles reported in previous articles.…”

Section: Resultscontrasting

confidence: 53%

“…Sulfur treatment has been known to have two effects: it can restrain the alkali elution from the surface of a glass vial due to dealkalization, 27,28) but it can also pit the surface of the vial and thus enhance delamination. 10,29) Considering the fact that sulfur treatment suppressed the particle formation, dealkalization might have an effect on the suppression of particle formation. In contrast, SiO 2 coating is also known to protect the surface from alkali elution, 2,12) however, no suppression effects of the SiO 2 coating on the particle formation were shown in this study.…”

Section: Resultsmentioning

confidence: 99%

“…[4][5][6][7][8][9] In addition to water, other elements in drug solutions are known to induce the collapse of glass surfaces. Ennis et al 10) evaluated the tendencies of delamination from borosilicate glass vials based on the fact that the cidofovir injectable drug product formed glass delamination, and they concluded that the high pH of the solution enhanced the corrosive attack on the inner surface of the glass container, resulting in delamination. Iacocca et al 11,12) also investigated causes of glass delamination using some drug products with borosilicate glass vials, suggesting a scheme of corrosive attacks by the drug solution on the glass surface, which relates to the delamination.…”

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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: Resultscontrasting

confidence: 53%

Section: Resultsmentioning

confidence: 99%

mentioning

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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“…14,15) According to numbers of research articles, the washing process is also known to enhance delamination as a result of causing pitting on the surface. 4,16) On the other hand, SiO 2 coating, a technique to coat the surface with silica, is known to be able to avoid delamination from the glass surface. 2,6) However, our previous study showed that sulfur-treated vials showed a protective effect against the Al-containing particles' formation, while otherwise the SiO 2 coating did not have any protective effects.…”

mentioning

confidence: 99%

“…Delamination, which is indicated by the presence of glass flakes, is the most well-known phenomenon and is the result of corrosive attack on the inner surface of the glass container. [4][5][6][7][8][9][10] United States Pharmacopeia (USP) ‹1660› describes factors of delamination on the surface of glass vials filled with drug solution, and also introduces tools for selecting an appropriate glass container from the point of view of avoiding delamination. 11) Among several literatures describing the propensity of forming delamination, Guadagnino has suggested that the silicon dioxide (SiO 2 ) concentration in an extract solution is an efficient indicator of glass dissolution.…”

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confidence: 99%

Comparisons of Aluminum and Silica Elution from Various Glass Vials

Ogawa

Miyajima

Nishimoto

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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To understand the risk of particle formation in glass vials, we investigated the correlation between vial surface condition and alminum (Al) or silicon (Si) elution using various suppliers' vials with or without surface treatment. The elution of Si, which can also be an indicator of Al elution, consists of two phases; the first phase is influenced by roughness of the glass surface at the time of filling, and the second phase is dependent on the fundamental elution rate from the glass tube. When vials were filled with citrate buffer at pH 7, vials with varied surface conditions showed the most obvious differences in Al and Si elution. Sulfur-treated vials showed slightly lower Al and Si elution than the non-treated vials. It is considered that this effect of the sulfur treatment on elution is due to the surface being smoothed during heat treatment after the washing process. Different from the sulfur treatment, silicon dioxide (SiO 2 )-coated vials hardly showed any Al elution as long as the surface was fully coated with the SiO 2 layer. It was found that the protective effect of the SiO 2 layer against Al elution is more effective in a vial filled with a solution having a lower pH, due to the lower Si dissolving rate occurring at a lower pH. As shown above, pre-measuring the Si and Al present in a citrate buffer at pH 7 placed within a glass container can be a useful tool for selecting the appropriate container for liquid drugs.Key words citrate buffer; borosilicate glass; tubing vial; sulfur treatment; silicon dioxide coating For injectable drugs, particularly liquid injectable drugs, evaluating compatibility between the drug solution and glass container is one of the most important factors to evaluate because the components of the drugs are always in contact with the surface of the packaging component during storage.

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Primary Container and Closure Selection for Biopharmaceuticals

Henderson

2010

Formulation and Process Development Strategies for Manufacturing Biopharmaceuticals

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Glass Vials for Small Volume Parenterals: Influence of Drug and Manufacturing Processes on Glass Delamination

Abstract: These results demonstrate the importance of the surface morphology created during the vial forming process. Given the diferences observed, final vial selection should include extensive microscopical and product stress testing studies on multiple vial lots.

Cited by 66 publications

References 6 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

Comparisons of Aluminum and Silica Elution from Various Glass Vials

Primary Container and Closure Selection for Biopharmaceuticals

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