A novel method of producing a microcrystalline beta-sitosterol suspension in oil.
This paper describes a novel method of producing a microcrystalline oral suspension containing beta-sitosterol in oil for the treatment of hypercholesterolaemia. beta-Sitosterol pseudopolymorphs with different water contents were crystallized from acetone and acetone-water solutions. Structural analyses of the crystals were performed by Karl-Fisher titration, thermogravimetric analyses, X-ray diffraction and near infrared spectroscopy. The suspensions studied were composed of different concentrations of beta-sitosterol, oil and water. Suspensions were prepared by crystallization of hot concentrated solution of beta-sitosterol in oil by cooling with simultaneous agitation and water addition. The structural analyses of the suspensions were performed by X-ray diffraction, near infrared spectroscopy and optical microscopy. The viscosity of the suspensions was analysed as a function of shear stress. beta-Sitosterol was observed to exist in three different forms: anhydrous, hemihydrated and monohydrated crystals. By changing both the beta-sitosterol and the water concentration of the suspension, the crystal size and shape could be controlled. Addition of water resulted in the formation of monohydrated needle-shaped crystals instead of platy-like anhydrous crystals. Needle-shaped particles formed structured suspensions with shear thinning behaviour. By increasing the volume fraction of solid particles in suspension by increasing the water and/or sterol concentration, the viscosity increased. A high sterol concentration resulted in high supersaturation and thus formation of small crystals.
Christiansen
Leena I
LI
Pharmaceutical Technology Division, Department of Pharmacy, PO Box 56, University of Helsinki, FIN-00014, Finland. leena.christiansen@helsinki.fi
Rantanen
Jukka T
JT
von Bonsdorff
Anna K
AK
Karjalainen
Milja A
MA
Yliruusi
Jouko K
JK
D000284:Administration, Oral; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D006937:Hypercholesterolemia / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000032:analysis / Q000138:chemical synthesis*; D009821:Oils / Q000008:administration & dosage / Q000032:analysis / Q000138:chemical synthesis*; D012212:Rheology; D012855:Sitosterols / Q000008:administration & dosage / Q000032:analysis / Q000138:chemical synthesis*; D019265:Spectroscopy, Near-Infrared; D013535:Suspensions; D013678:Technology, Pharmaceutical / Q000379:methods*; D013818:Thermogravimetry; D014961:X-Ray Diffraction
D000960:Hypolipidemic Agents; D009821:Oils; D012855:Sitosterols; D013535:Suspensions; C025473:gamma-sitosterol