A Generalized Relation for Solid-State Drug Stability as a Function of Excipient Dilution: Temperature-Independent Behavior

Waterman, Kenneth C.; Gerst, Paul H.; Dai, Zhijun

doi:10.1002/jps.23268

Cited by 15 publications

(11 citation statements)

References 4 publications

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“…A kinetic model for the degradation of crystalline drugs as a function of excipient dilution predicted increased degradation as a function of the surface area of contact between crystalline small molecules and excipient molecules (Waterman and others ). Significantly more AA loss in physical blends of crystalline AA with PVP at decreasing vitamin : polymer ratios was not found.…”

Section: Resultsmentioning

confidence: 99%

Degradation of L‐Ascorbic Acid in the Amorphous Solid State

Sanchez

Ismail

Christina

et al. 2018

Journal of Food Science

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Vitamin C is one of the most unstable vitamins in foods. This study documents that amorphous ascorbic acid is less stable than crystalline ascorbic acid in some environments (for example, higher temperatures within 1 wk), especially when the vitamin is present at low concentrations in a product. These findings increase the understanding of how material science properties influence the stability of vitamin C.

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Section: Resultsmentioning

confidence: 99%

Degradation of L‐Ascorbic Acid in the Amorphous Solid State

Sanchez

Ismail

Christina

et al. 2018

Journal of Food Science

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“…For example, when phenol red was incorporated in a suspension of ground calcium carbonate (CalciPure GCC-300) in methanol, visual observation of the suspension suggested that the indicator was unionized in the methanol supernatant (yellow) but was significantly ionized (pink) when adsorbed on the solid surface of the settled calcium carbonate (9). It should also be stressed that the impact of excipients on the stability of the API can be affected by extent of contact between particles of API and excipient, and therefore can be expected to depend on the particle size and API/excipient ratio (34). In addition, apparent acidity of solid surfaces may depend on the solid structure in some cases, and therefore can be impacted by potential structural changes during solid-state processing.…”

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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“…[83] It has been observed that typically the stability of API can be significantly influenced by mixing with excipients. [83] Generally, the degrada-tion rates are found to increase as drug loading is decreased so accelerated studies are carried out at low drug loadings. The process of making a dosage form will require the API to come into contact with other materials (excipients) to form interfaces.…”

Section: Shelf Life (Stability)mentioning

confidence: 99%

“…During formulation development, the stability of an API and API in drug product is typically measured experimentally under accelerated conditions [83]. It has been observed that typically the stability of API can be significantly influenced by mixing with excipients [83]. Generally, the degradation rates are found to increase as drug loading is decreased so accelerated studies are carried out at low drug loadings.…”

Section: The Role Of Api Properties Solid Form and Particle Engineermentioning

confidence: 99%

Integration of active pharmaceutical ingredient solid form selection and particle engineering into drug product design

Ticehurst

Marziano

2015

Journal of Pharmacy and Pharmacology

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This review seeks to offer a broad perspective that encompasses an understanding of the drug product attributes affected by active pharmaceutical ingredient (API) physical properties, their link to solid form selection and the role of particle engineering. While the crucial role of active pharmaceutical ingredient (API) solid form selection is universally acknowledged in the pharmaceutical industry, the value of increasing effort to understanding the link between solid form, API physical properties and drug product formulation and manufacture is now also being recognised.A truly holistic strategy for drug product development should focus on connecting solid form selection, particle engineering and formulation design to both exploit opportunities to access simpler manufacturing operations and prevent failures. Modelling and predictive tools that assist in establishing these links early in product development are discussed. In addition, the potential for differences between the ingoing API physical properties and those in the final product caused by drug product processing is considered. The focus of this review is on oral solid dosage forms and dry powder inhaler products for lung delivery.

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A Generalized Relation for Solid-State Drug Stability as a Function of Excipient Dilution: Temperature-Independent Behavior

Cited by 15 publications

References 4 publications

Degradation of L‐Ascorbic Acid in the Amorphous Solid State

Degradation of L‐Ascorbic Acid in the Amorphous Solid State

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

Integration of active pharmaceutical ingredient solid form selection and particle engineering into drug product design

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