title: Preparation of amorphous solid dispersions by rotary evaporation and KinetiSol Dispersing: approaches to enhance solubility of a poorly water-soluble gum extract.
abstract: Acetyl-11-keto-β-boswellic acid (AKBA), a gum resin extract, possesses poor water-solubility that limits bioavailability and a high melting point making it difficult to successfully process into solid dispersions by fusion methods. The purpose of this study was to investigate solvent and thermal processing techniques for the preparation of amorphous solid dispersions (ASDs) exhibiting enhanced solubility, dissolution rates and bioavailability. Solid dispersions were successfully produced by rotary evaporation (RE) and KinetiSol® Dispersing (KSD). Solid state and chemical characterization revealed that ASD with good potency and purity were produced by both RE and KSD. Results of the RE studies demonstrated that AQOAT®-LF, AQOAT®-MF, Eudragit® L100-55 and Soluplus with the incorporation of dioctyl sulfosuccinate sodium provided substantial solubility enhancement. Non-sink dissolution analysis showed enhanced dissolution properties for KSD-processed solid dispersions in comparison to RE-processed solid dispersions. Variances in release performance were identified when different particle size fractions of KSD samples were analyzed. Selected RE samples varying in particle surface morphologies were placed under storage and exhibited crystalline growth following solid-state stability analysis at 12 months in comparison to stored KSD samples confirming amorphous instability for RE products. In vivo analysis of KSD-processed solid dispersions revealed significantly enhanced AKBA absorption in comparison to the neat, active substance.
authors: Division of Pharmaceutics, The University of Texas at Austin , Austin, TX , USA .
authors: Ryan C
authors: RC
authors: Bennett
authors: Chris
authors: C
authors: Brough
authors: Dave A
authors: DA
authors: Miller
authors: Kevin P
authors: KP
authors: O'Donnell
authors: Justin M
authors: JM
authors: Keen
authors: Justin R
authors: JR
authors: Hughey
authors: Robert O
authors: RO
authors: Williams
authors: James W
authors: JW
authors: McGinity
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D065260:Frankincense / Q000138:chemical synthesis* / Q000378:metabolism; D008297:Male; D053149:Plant Gums / Q000138:chemical synthesis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014315:Triterpenes / Q000138:chemical synthesis* / Q000378:metabolism; D014867:Water / Q000737:chemistry* / Q000378:metabolism; D014961:X-Ray Diffraction
chemical_list: D053149:Plant Gums; D014315:Triterpenes; C094432:acetyl-11-ketoboswellic acid; D014867:Water; D065260:Frankincense
keywords: Amorphous solid dispersions; KinetiSol Dispersing; bioavailability enhancement; hot melt extrusion; rotary evaporation; supersaturation