Effect of Moisture on the Stability of Solid Dosage Forms

Carstensen, J.T.

doi:10.3109/03639048809151998

Cited by 74 publications

(25 citation statements)

References 9 publications

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“…The released water, even in small amounts, may be transferred to other components of the formulation, affecting the chemical and physical stability. 8 The observed improvement in flow may provide a sufficient reason for milling commercial aspartame hemihydrate, but if the aspartame formulation is moisturesensitive, the greater ease of dehydration of the ball-milled polymorph (I) should also be considered.…”

Section: Resultsmentioning

confidence: 98%

Hydration and Dehydration Behavior of Aspartame Hemihydrate

Leung

Padden

Munson

et al. 1998

Journal of Pharmaceutical Sciences

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Previous studies have shown that aspartame in the solid state can exist as a hemihydrate which occurs in two different polymorphic forms (I and II). The present work shows that equilibration of either hemihydrate at 25 degrees C with water vapor at relative humidities > or = 58% or with liquid water produces a 2.5-hydrate. Upon subjecting each of these crystalline hydrates to increasing temperature, the same crystalline anhydrate is formed which thermally cyclizes at a higher temperature to form the known compound 3-(carboxymethyl)-6-benzyl-2,5-dioxopiperazine. The activation energy of the cyclization reaction appears to depend on the degree of crystallinity of the anhydrate that is formed at a lower temperature. On increasing the temperature of the 2.5-hydrate, a hemihydrate intervenes before the anhydrate is formed. This intervening hemihydrate is similar to the commercial form (II) of aspartame hemihydrate but exhibits greater amorphous character. The techniques employed were Karl Fischer titrimetry, powder X-ray diffractometry, differential scanning calorimetry, thermogravimetric analysis, solid-state 13C nuclear magnetic resonance spectroscopy, and Fourier transform infrared absorption spectroscopy.

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Section: Resultsmentioning

confidence: 98%

Hydration and Dehydration Behavior of Aspartame Hemihydrate

Leung

Padden

Munson

et al. 1998

Journal of Pharmaceutical Sciences

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“…Four of the impurity peaks were successfully identified. These corresponded (in order of elution time) to ranitidine-related compounds [6] and/or [7], [3], [10] and [9], as shown in Fig. 3 either ranitidineYN-oxide [6] or ranitidineYS-oxide [7].…”

Section: Lc/ms Of Original and Degraded Samples Of Ranitidinementioning

confidence: 99%

Effect of Small Levels of Impurities on the Water Vapor Sorption Behavior of Ranitidine HCl

2006

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It was concluded that small levels of degradants and/or impurities can drastically affect the moisture sorption profile of a deliquescent material, both through affecting the deliquescence relative humidity and by altering the overall interaction of the substance with moisture. Such changes in behavior may have significant effects on both active pharmaceutical ingredient and drug product stability during both processing and storage.

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“…Hydrolysis and decarboxylation occur due to presence of sorbed moisture, which is invariably present in the drug substance. According to Carstensen (1988), on subjecting a drug substance with sorbed moisture to stress the entire process of degradation is considered to equal the sum of the decomposition in the bulk solid state and that in the drug saturated aqueous layer at interface.…”

Section: Proposed Mechanism Of Degradationmentioning

confidence: 99%