Towards an Understanding of the Structurally Based Potential for Mechanically Activated Disordering of Small Molecule Organic Crystals

Wildfong, Peter L.D.; Hancock, Bruno C.; Moore, Michael D.; Morris, Kenneth R.

doi:10.1002/jps.20672

Cited by 78 publications

(78 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2 These defects represent regions of higher disorder relative to the three-dimensional longrange order expected and, hence, introduce a higher level of energy to the solid. 3 Pharmaceutical interest in such defects arises from the demonstrated role that these high energy sites can play in affecting a number of important physical and chemical phenomena, including higher dissolution rates, 4 greater chemical instability, 5,6 altered mechanical properties, [7][8][9] and enhanced hygroscopicity. 10,11 Such effects of disorder on solid-state properties of crystals also occur when the solid is converted fully or in part to the amorphous state, such that it has lost longrange order but has retained the short-range order observed with liquids.…”

Section: Introductionmentioning

confidence: 99%

Assessment of Defects and Amorphous Structure Produced in Raffinose Pentahydrate upon Dehydration

Bates

Kelly

Ivanisevic

et al. 2007

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Assessment of Defects and Amorphous Structure Produced in Raffinose Pentahydrate upon Dehydration

Bates

Kelly

Ivanisevic

et al. 2007

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

“…Process-induced structural disorder can lead to uncontrolled thermodynamic changes to the materials and is commonly described as "mechanical activation" (4)(5)(6)(7). Mechanical activation may directly influence the physicochemical properties of a substance, for example, surface free energy, reactivity, conductivity, and true density (6,8).…”

Section: Introductionmentioning

confidence: 99%

The Influence of Secondary Processing on the Structural Relaxation Dynamics of Fluticasone Propionate

et al. 2014

View full text Add to dashboard Cite

ABSTRACT. This study investigated the structural relaxation of micronized fluticasone propionate (FP) under different lagering conditions and its influence on aerodynamic particle size distribution (APSD) of binary and tertiary carrier-based dry powder inhaler (DPI) formulations. Micronized FP was lagered under low humidity (LH 25 C, 33% RH [relative humidity]), high humidity (HH 25°C, 75% RH) for 30, 60, and 90 days, respectively, and high temperature (HT 60°C, 44% RH) for 14 days. Physicochemical, surface interfacial properties via cohesive-adhesive balance (CAB) measurements and amorphous disorder levels of the FP samples were characterized. Particle size, surface area, and rugosity suggested minimal morphological changes of the lagered FP samples, with the exception of the 90-day HH (HH90) sample. HH90 FP samples appeared to undergo surface reconstruction with a reduction in surface rugosity. LH and HH lagering reduced the levels of amorphous content over 90-day exposure, which influenced the CAB measurements with lactose monohydrate and salmeterol xinafoate (SX). CAB analysis suggested that LH and HH lagering led to different interfacial interactions with lactose monohydrate but an increasing adhesive affinity with SX. HT lagering led to no detectable levels of the amorphous disorder, resulting in an increase in the adhesive interaction with lactose monohydrate. APSD analysis suggested that the fine particle mass of FP and SX was affected by the lagering of the FP. In conclusion, environmental conditions during the lagering of FP may have a profound effect on physicochemical and interfacial properties as well as product performance of binary and tertiary carrier-based DPI formulations.

show abstract

“…Disordered particles obtained via milling are also susceptible to increased water sorption which can influence its physical state as seen for albuterol sulfate (8) and also to increased chemical instability (9). However, not all compounds are influenced to the same extent upon mechanical impaction, and the propensity of a compound to form a disordered or amorphous state upon milling depends on the crystal structure of the material (10).…”

Section: Introductionmentioning

confidence: 99%

Mechanically Induced Amorphization of Drugs: A Study of the Thermal Behavior of Cryomilled Compounds

Trasi

Byrn

2012

AAPS PharmSciTech

View full text Add to dashboard Cite

Abstract. The purpose of this work was to determine what aspect of the milled compound influences its thermal profile. For this, six different compounds with different properties were chosen and cryomilled for different times to get an amorphous solid. Differential scanning calorimetry (DSC) and X-ray powder diffraction were used to characterize the material and look at the thermal behavior. Melt-quenched samples were also prepared, and the thermal profile upon milling was determined and correlated with the thermal behavior of the cryomilled samples. Growth rates were determined by hot-stage microscopy. Ketoconazole, when cryomilled, showed only one crystallization exotherm in the DSC profile. Ursodiol, and to some extent indomethacin, initially showed a double exotherm which eventually become a single exotherm on further milling. Griseofulvin, carbamazepine, and piroxicam exhibited a double exotherm in the DSC profile upon cryomilling to the amorphous state. Surface crystal growth rates around T g were found to be highest for compounds showing the double exotherm in the DSC. Thus, it was seen that compounds which have high surface crystallization tendency will exhibit the double exotherm during heating.

show abstract

Towards an Understanding of the Structurally Based Potential for Mechanically Activated Disordering of Small Molecule Organic Crystals

Cited by 78 publications

References 48 publications

Assessment of Defects and Amorphous Structure Produced in Raffinose Pentahydrate upon Dehydration

Assessment of Defects and Amorphous Structure Produced in Raffinose Pentahydrate upon Dehydration

The Influence of Secondary Processing on the Structural Relaxation Dynamics of Fluticasone Propionate

Mechanically Induced Amorphization of Drugs: A Study of the Thermal Behavior of Cryomilled Compounds

Contact Info

Product

Resources

About