TY - JOUR
T1 - Impact of crystal habit on biopharmaceutical performance of celecoxib
AU - Modi, Sameer R.
AU - Dantuluri, Ajay K.R.
AU - Puri, Vibha
AU - Pawar, Yogesh B.
AU - Nandekar, Prajwal
AU - Sangamwar, Abhay T.
AU - Perumalla, Sathyanarayana R.
AU - Sun, Changquan Calvin
AU - Bansal, Arvind K.
PY - 2013/7/3
Y1 - 2013/7/3
N2 - 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 Cmax and shorter Tmax 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.
AB - 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 Cmax and shorter Tmax 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.
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U2 - 10.1021/cg400140a
DO - 10.1021/cg400140a
M3 - Article
AN - SCOPUS:84879864016
SN - 1528-7483
VL - 13
SP - 2824
EP - 2832
JO - Crystal Growth and Design
JF - Crystal Growth and Design
IS - 7
ER -