Formulation and performance of danazol nano-crystalline suspensions and spray dried powders.
OBJECTIVE
This study focuses on the formulation optimization, in vitro and in vivo performance of differently sized nano-crystalline liquid suspensions and spray-dried powders of a poorly soluble BCS class II compound i.e. Danazol.


METHODS
A DoE approach was utilized to optimize stabilizer concentration and formulate danazol (BCS class II) nano-crystalline suspensions and dry powders via wet milling followed by spray drying. Solubility studies were performed to select best stabilizers. Particle size, PXRD, contact angle measurement and in vitro dissolution were utilized in characterization of the liquid and spray-dried powder formulations.


RESULTS
The liquid nano-crystalline suspensions followed particle size-dependent dissolution rates i.e. faster dissolution for smaller crystals. The spray-dried nano-crystal powders did not show fast dissolution profiles compared to the liquid nano-crystalline suspension. The poor dissolution of the spray-dried powder correlated to its high LogP value (i.e. LogP 4.53) and poor wetting (or polar surface-area). In vivo bioavailability studies showed superior performance of the liquid nano-crystalline suspensions compared to other milled and un-milled formulations.


CONCLUSIONS
Wet-milling and spray-drying optimization for danazol nano-crystalline suspension was performed. This study indicates that drug candidates with high LogP values and low polar surface area may not be suitable for formulation as dry nano-crystals.
Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, 69 N Eagleville Road, Unit 3092, Storrs, Connecticut, 06269, USA.
Sumit
S
Kumar
Rajan
R
Jog
Jie
J
Shen
Banu
B
Zolnik
Nakissa
N
Sadrieh
Diane J
DJ
Burgess
D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D003613:Danazol / Q000737:chemistry*; D003890:Desiccation; D004965:Estrogen Antagonists / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D011208:Powders; D012995:Solubility; D013535:Suspensions
D004965:Estrogen Antagonists; D005079:Excipients; D011208:Powders; D013535:Suspensions; D003613:Danazol