Physical stability of micronized powders produced by spray-freezing into liquid (SFL) to enhance the dissolution of an insoluble drug.
OBJECTIVE
The objective of this study was to investigate the physical stability of micronized powders produced by the spray-freezing into liquid (SFL) particle engineeringtechnology.


METHODS
Danazol was formulated with polyvinyl alcohol (MW 22,000), poloxamer 407, and polyvinylpyrrolidone K-15 to form a cosolvent solution that was SFL processed. The dried micronized SFL powders were sealed in glass vials with desiccant and exposed to 25 degrees C/60% RH for 3 and 6 mo, 40 degrees C/75% RH for 1, 2, 3, and 6 mo, and conditions where the temperature was cycled between -5 and +40 degrees C (6 cycles/24 hr) with constant 75% RH for 1, 2, 3 and 4 wk. The samples were characterized by using Karl-Fisher titration, differential scanning calorimetry, x-ray diffraction, specific surface area, scanning electron microscopy, and dissolution testing.


RESULTS
Micronized SFL powders consisting of porous aggregates with small-particle domains were characterized as having high surface areas and consisted of amorphous danazol embedded within a hydrophilic excipient matrix. Karl-Fischer titration revealed no moisture absorption over the duration of the stability studies. Differential scanning calorimetry studies demonstrated high degrees of molecular interactions between danazol, PVA, poloxamer, and PVP. Scanning electron microscopy studies confirmed these interactions, especially those between danazol and poloxamer. These interactions facilitated API dissolution in the aqueous media. Powder surface area remained constant during storage at the various stability conditions, and danazol recrystallization did not occur during the entirety of the stability studies. Micronized SFL powders containing danazol dissolved rapidly and completely within 5 min in aqueous media. No differences were observed in the enhanced dissolution profiles of danazol after exposure to the storage conditions investigated. Physically stable micronized powders produced by the SFL particle engineering technology were produced for the purpose of enhancing the dissolution of an insoluble drug.


CONCLUSIONS
The potential of the SFL particle-engineering technology as a micronization technique for enhancing the dissolution of hydrophobic drugs was demonstrated in this study. The robustness of the micronized SFL powders to withstand stressed storage conditions was shown.
Rogers
True L
TL
College of Pharmacy, University of Texas at Austin, Austin, Texas 78712-1074, USA.
Johnston
Keith P
KP
Williams
Robert O
RO
D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D005079:Excipients; D005615:Freezing; D006813:Humidity; D011208:Powders / Q000737:chemistry*; D012995:Solubility; D012996:Solutions; D013696:Temperature; D014961:X-Ray Diffraction
D005079:Excipients; D011208:Powders; D012996:Solutions