Simultaneous determination of formic acid and formaldehyde in pharmaceutical excipients using headspace GC/MS

Barrio, Mary-Anne del; Hu, Jack; Zhou, Pengzu; Cauchon, Nina S.

doi:10.1016/j.jpba.2005.12.033

Cited by 95 publications

(52 citation statements)

References 19 publications

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“…As can be seen in Figure 2, the relative amount of formaldehyde produced is heavily affected by the amount of CA present, consistent with the concept that PEG that is less mobile due to interactions with CA, shows less degradation. It should be noted that subsequent to this work, a method was reported in the literature 22 for simultaneous determination of formaldehyde and formic acid using headspace GC/MS.…”

Section: Resultsmentioning

confidence: 99%

N‐Methylation and N‐Formylation of a Secondary Amine Drug (Varenicline) in an Osmotic Tablet

Waterman

Arikpo

Fergione

et al. 2008

Journal of Pharmaceutical Sciences

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Section: Resultsmentioning

confidence: 99%

N‐Methylation and N‐Formylation of a Secondary Amine Drug (Varenicline) in an Osmotic Tablet

Waterman

Arikpo

Fergione

et al. 2008

Journal of Pharmaceutical Sciences

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“…A similar mechanism, i.e., generation of an acid during storage, could be applicable to calcium acetate hydrate, which was shown to promote acid-catalyzed degradation of the API in the present study. In addition, acidic impurities were reported in hydroxypropyl methylcellulose (up to 100 ppm), povidone (up to 1000 ppm), and sodium starch glycolate (up to 140 ppm) (30,31). Therefore, both the low pH eq and the incompatibility of atorvastatin calcium with Polyplasdone XL (crospovidone), PROSOLV SMCC 90 (silicified microcrystalline cellulose), EXPLOTAB® (sodium starch glycolate), observed in this study, may be attributed, at least in part, to the presence of acidic impurities on the surface of these excipients.…”

Section: Discussionmentioning

confidence: 99%

Surface Acidity and Solid-State Compatibility of Excipients with an Acid-Sensitive API: Case Study of Atorvastatin Calcium

et al. 2014

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Abstract. The objectives of this study were to measure the apparent surface acidity of common excipients and to correlate the acidity with the chemical stability of an acid-sensitive active pharmaceutical ingredient (API) in binary API-excipient powder mixtures. The acidity of 26 solid excipients was determined by two methods, (i) by measuring the pH of their suspensions or solutions and (ii) the pH equivalent (pH eq ) measured via ionization of probe molecules deposited on the surface of the excipients. The chemical stability of an API, atorvastatin calcium (AC), in mixtures with the excipients was evaluated by monitoring the appearance of an acid-induced degradant, atorvastatin lactone, under accelerated storage conditions. The extent of lactone formation in AC-excipient mixtures was presented as a function of either solution/suspension pH or pH eq . No lactone formation was observed in mixtures with excipients having pH eq > 6, while the lactone levels were pronounced (> 0.6% after 6 weeks at 50°C/20% RH) with excipients exhibiting pH eq < 3. The three pH eq regions (> 6, 3-6, and < 3) were consistent with the reported solution pH-stability profile of AC. In contrast to the pH eq scale, lactone formation did not show any clear trend when plotted as a function of the suspension/solution pH. Two mechanisms to explain the discrepancy between the suspension/solution pH and the chemical stability data were discussed. Acidic excipients, which are expected to be incompatible with an acid-sensitive API, were identified based on pH eq measurements. The incompatibility prediction was confirmed in the chemical stability tests using AC as an example of an acid-sensitive API.

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“…1) is most likely formed in the tablets by the reaction with formic acid. Organic acids, such as formic acid, are common impurities in poly(ethylene glycol) (PEG), hydroxypropyl methylcellulose (HPMC), povidone, and polyvinyl alcohol (6,12). Often, excipients with formaldehyde impurities also contain some formic acid due to oxidation of formaldehyde to formic acid by atmospheric oxygen.…”

Section: Effect Of Different Odt Platforms On Benzocaine Stabilitymentioning

confidence: 99%

Stability of Benzocaine Formulated in Commercial Oral Disintegrating Tablet Platforms

et al. 2013

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Abstract. Pharmaceutical excipients contain reactive groups and impurities due to manufacturing processes that can cause decomposition of active drug compounds. The aim of this investigation was to determine if commercially available oral disintegrating tablet (ODT) platforms induce active pharmaceutical ingredient (API) degradation. Benzocaine was selected as the model API due to known degradation through ester and primary amino groups. Benzocaine was either compressed at a constant pressure, 20 kN, or at pressure necessary to produce a set hardness, i.e., where a series of tablets were produced at different compression forces until an average hardness of approximately 100 N was achieved. Tablets were then stored for 6 months under International Conference on Harmonization recommended conditions, 25°C and 60% relative humidity (RH), or under accelerated conditions, 40°C and 75% RH. Benzocaine degradation was monitored by liquid chromatography-mass spectrometry. Regardless of the ODT platform, no degradation of benzocaine was observed in tablets that were kept for 6 months at 25°C and 60% RH. After storage for 30 days under accelerated conditions, benzocaine degradation was observed in a single platform. Qualitative differences in ODT platform behavior were observed in physical appearance of the tablets after storage under different temperature and humidity conditions.

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Simultaneous determination of formic acid and formaldehyde in pharmaceutical excipients using headspace GC/MS

Cited by 95 publications

References 19 publications

N‐Methylation and N‐Formylation of a Secondary Amine Drug (Varenicline) in an Osmotic Tablet

N‐Methylation and N‐Formylation of a Secondary Amine Drug (Varenicline) in an Osmotic Tablet

Surface Acidity and Solid-State Compatibility of Excipients with an Acid-Sensitive API: Case Study of Atorvastatin Calcium

Stability of Benzocaine Formulated in Commercial Oral Disintegrating Tablet Platforms

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