Impact of Crystal Habit on Biopharmaceutical Performance of Celecoxib

Abstract

Poor biopharmaceutical performance of Biopharmaceutical Classification System (BCS) class II drug molecules is a major hurdle in the design and development of pharmaceutical formulations. Anisotropic surface chemistry of different facets in crystalline material affects physicochemical properties, such as wettability, of drugs. In the present investigation, a molecule-centered approach is presented toward crystal habit modification of celecoxib (CEL) and its effect on oral bioavailability. Two crystal habits of CEL, acicular crystal habit (CEL-A) and a plate-shaped crystal habit (CEL-P), were obtained by recrystallization from toluene at 25 and 60 °C, respectively. Compared to CEL-A, CEL-P exhibited significantly faster dissolution kinetics in aqueous media and significantly higher C max and shorter T max in an oral bioavailability study. The significant enhancement in dissolution and biopharmaceutical performance of CEL-P was attributed to its more abundant hydrophilic surfaces compared to CEL-A. This conclusion was supported by wettability and surface free energy determination from contact angle measurements and surface chemistry determination by X-ray photoelectron spectroscopy (XPS), crystal structure modeling, and crystal face indexation.

Cocrystal habit engineering to improve drug dissolution and alter derived powder properties

“…The slope of the tangent to the drop at the liquid–solid–vapour interface line was calculated. All measurements were performed in triplicate under ambient conditions of 25 ± 2°C [7]…”

“…However, two other factors, ‘polymorphism’ and ‘crystal habit’, play a key role in the physicochemical properties of the API and then in its overall biopharmaceutical performance in vivo . Polymorphism is the ability of a drug to pack into different crystal lattice arrangements, whereas crystal habit is the external appearance of the crystal [7,8]…”

Crystal growth of barium nitrate on thiol-terminated self-assembled monolayers and a Raman spectroscopic investigation of the crystal facets

“…For example, the dissolution rates and bioavailabilities of pharmaceutical compounds are largely dependent on their crystal habits [19,20]. Generally, there are two methods that are frequently used to predict crystal habits.…”

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

“…that assume an average contact angle over the whole particle, it is important to consider the anisotropic nature of crystals and that each face has its own specific surface properties. Modi et al [17]. assessed the impact of particle shape (crystal habit) on the dissolution rate over and above the effect on total surface area using celecoxib as a model API.…”

“…These API properties are also linked to each other, for instance, surface chemistry can be linked to particle morphology, which in turn is influenced by intrinsic lattice properties (and as such is dependent on solid form) and the crystallisation solvents employed. This was illustrated by a recent literature report where particle engineering was used to change the particle morphology of celecoxib, resulting in a change in the relative amount of more hydrophilic crystal faces and increased dissolution rate [17]. Similarly, the ease of particle breakage during milling, which could be important to reach a target particle size, is linked to lattice‐dependent mechanical properties such as brittleness [18].…”