Decoupling the Eeffects of Esurface Chemistry and Humidity on Solid-State Hydrolysis of Aspirin in the Presence of Dicalcium Phosphate Dihydrate

Cassidy, Andrew; Gardner, Catherine E.; Auffret, Tony; Aldous, Barry J.; Jones, William

doi:10.1002/jps.23038

Cited by 7 publications

(6 citation statements)

References 32 publications

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“…As a result, moisture in the environment is readily available to degrade the ASA. Hydrolysis of ASA in the presence of DCP has also been explained based on the force of adhesion ( f adh ) between DCP and ASA as measured using atomic force microscopy . At RH greater than 40%, a moisture layer forms on the ASA hydrophilic surfaces, and there is a strong increment in the f adh between DCP and ASA.…”

Section: Discussionmentioning

confidence: 99%

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Relative Humidity Cycling: Implications on the Stability of Moisture-Sensitive Drugs in Solid Pharmaceutical Products

2022

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The stability of a moisture-sensitive drug in tablet formulations depends particularly on the environment's relative humidity (RH) and the products' prior exposure to moisture. This study was designed to understand drug stability in relation to the moisture interaction of the excipients, moisture history of the tablets, and RH of the environment. The stability study was performed on tablets containing acetylsalicylic acid (ASA), formulated with common pharmaceutical excipients like native maize starch, microcrystalline cellulose (MCC), partially pregelatinized maize starch (PGS), dicalcium phosphate dihydrate (DCP), lactose, and mannitol. The tablets were subjected to storage conditions with RH cycling alternating between 53% and 75%. Results were also compared to tablets stored at a constant RH of 53% or 75%. The excipients demonstrated marked differences in their interactions with moisture. They could be broadly grouped as excipients with RH-dependent moisture content (native maize starch, MCC, and PGS) and RH-independent moisture content (DCP, lactose, and mannitol). As each excipient interacted differently with moisture, degradation of ASA in the tablets depended on the excipients' ability to modulate the moisture availability for degradation. The lowest ASA degradation was observed in tablets formulated with low moisture content water-soluble excipients, such as lactose and mannitol. The impact of RH cycling on ASA stability was apparent in tablets containing native maize starch, MCC, PGS, or DCP. These findings suggested that the choice of excipients influences the effect of moisture history on drug stability. The results from studies investigating moisture interaction of excipients and drug stability are valuable to understanding the inter-relationship between excipients, moisture history, and drug stability.

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Section: Discussionmentioning

confidence: 99%

“…The formulations generally had good flow and tableted well. The linear speed of the upper and lower punches was 35 Elevated RH was maintained at 75% ± 2% with a saturated salt slurry of NaCl. For RH cycling, the tablets were first exposed to 53% RH for 3 days and then 75% RH for another 3 days.…”

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confidence: 99%

Relative Humidity Cycling: Implications on the Stability of Moisture-Sensitive Drugs in Solid Pharmaceutical Products

2022

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“…In the case of aspirin (acetylsalicylic acid) and dicalcium phosphate, when the excipient was attached to the tip of the AFM cantilever and different pressures and contact times under various humidity conditions there was evidence for enhanced reactivity induced by surface contact with excipient. 91 Terahertz spectroscopy has emerged as a sensitive method of monitoring changes in the solid form during mechanical activation, 56,156 whereas TEM has been shown to be a powerful technique for characterising the size and shape of particulates generated mechanochemically, as well as determining their crystal form (see Fig. 20).…”

Section: Discussionmentioning

confidence: 99%

“…When pressure is applied during compression, there is a risk that surface-surface reactions between the components and drug, such as that between dicalcium phosphate dihydrate and aspirin, will lead to enhanced instability. 91 More recent interest has focused on the formation of cocrystals (see Fig. 9) by milling or grinding.…”

Section: Pharmaceutical Materialsmentioning

confidence: 99%

Introductory Lecture: Mechanochemistry, a versatile synthesis strategy for new materials

2014

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Mechanochemistry deals with reactions induced by the input of mechanical energy - for example by impacts within a vibratory ball mill. The technique has a long history with significant contributions from Ostwald, Carey Lea and, notably, Faraday. Mechanochemistry has subsequently seen application in a variety of areas of materials science including mechanical alloying in metallurgy, the synthesis of complex organic molecules and, more recently, the discovery and development of new solid forms of active pharmaceutical ingredients. This paper overviews the broad areas of application of mechanochemistry, some key features which make it a particularly attractive approach to materials synthesis and some mechanistic aspects highlighted within the literature. A significant part, however, will focus on recent applications in the area of pharmaceuticals and its important role in exploring the rich variety of solid forms available for small, drug-like, molecules.

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“… 11 Indeed recent studies on the differences in surface structure at the nanoscale have proven informative about the polymorphic outcome of crystallisation, 12,13 phase transitions, 14 thermal 15 and fluorescence 16 properties. In the case of aspirin, 17 for example, it has been shown that the well-known incompatibility of aspirin crystals with the excipient dicalcium phosphate dihydrate was related to the stronger interaction on one of the facets of aspirin surfaces.…”

Section: Introductionmentioning

confidence: 99%

Understanding stress-induced disorder and breakage in organic crystals: beyond crystal structure anisotropy

et al. 2021

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Decoupling the Eeffects of Esurface Chemistry and Humidity on Solid-State Hydrolysis of Aspirin in the Presence of Dicalcium Phosphate Dihydrate

Cited by 7 publications

References 32 publications

Relative Humidity Cycling: Implications on the Stability of Moisture-Sensitive Drugs in Solid Pharmaceutical Products

Relative Humidity Cycling: Implications on the Stability of Moisture-Sensitive Drugs in Solid Pharmaceutical Products

Introductory Lecture: Mechanochemistry, a versatile synthesis strategy for new materials

Understanding stress-induced disorder and breakage in organic crystals: beyond crystal structure anisotropy

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