Rapid dissolution of high-potency danazol particles produced by evaporative precipitation into aqueous solution.
High-potency danazol particles with high dissolution rates were produced by evaporative precipitation into aqueous solution (EPAS). Aqueous suspensions formed by EPAS were centrifuged to remove the nonadsorbed surfactant. The resulting surfactant-coated drug particles had extremely high drug-to-surfactant ratios greater than 5, corresponding to potencies (wt drug/wt drug + wt surfactant) as high as 93%. The mechanism of the high dissolution rates was characterized as a function of surfactant adsorption, particle size and surface area, drug crystallinity, and the contact angle for water on the drug surface. For danazol stabilized by polyvinyl pyrrolidone (PVP) alone or with sodium lauryl sulfate (SLS), small particle diameter and high surface area led to high dissolution rates with approximately 90% drug dissolved in 2 min. The crystallinity of the danazol was typically 80%. The properties of the particles and the dissolution rates were mostly unchanged under a 2-week thermal cycling stress test.
Chen
Xiaoxia
X
Department of Chemical Engineering, University of Texas at Austin, 78712, USA.
Vaughn
Jason M
JM
Yacaman
Miguel J
MJ
Williams
Robert O
RO
Johnston
Keith P
KP
D011232:Chemical Precipitation; D003613:Danazol / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D010316:Particle Size; D019999:Pharmaceutical Solutions / Q000138:chemical synthesis / Q000493:pharmacokinetics; D044367:Phase Transition; D012995:Solubility / Q000187:drug effects; D014867:Water / Q000737:chemistry* / Q000378:metabolism*
D019999:Pharmaceutical Solutions; D014867:Water; D003613:Danazol