Enhanced dissolution, stability and physicochemical characterization of ATRA/2-hydroxypropyl-β-cyclodextrin inclusion complex pellets prepared by fluid-bed coating technique.
The aim of this work was to prepare stable all-trans-retinoic acid (ATRA)/2-hydroxypropyl-β-cyclodextrin (HPCD) inclusion complex pellets with industrial feasible technology, the fluid-bed coating technique, using PVP K30 simultaneously as binder and reprecipitation retarder. The coating process was fluent with high coating efficiency. In vitro dissolution of the inclusion complex pellets in 5% w/v Cremopher EL solution was dramatically enhanced with no reprecipitation observed, and significantly improved stability against humidity (92.5% and 75% RH) and illumination (4500 lx ± 500 lx) was achieved by HPCD inclusion. Differential scanning calorimetry and powder X-ray diffractometry confirmed the absence of crystallinity of ATRA. Fourier transform-infrared spectrometry revealed interaction between ATRA and HPCD adding evidence on inclusion of ATRA moieties into HPCD cavities. Solid-state (13)C NMR spectrometry indicated possible inclusion of ATRA through the polyene chain, which was the main reason for the enhanced photostability. It is concluded that the fluid-bed coating technique has the potential use in the industrial preparation of ATRA/HPCD inclusion complex pellets.
School of Pharmacy, Fudan University, Shanghai 201203, China.
Zhongjian
Z
Chen
Yi
Y
Lu
Jianping
J
Qi
Wei
W
Wu
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D011232:Chemical Precipitation; D003460:Crystallization; D004304:Dosage Forms; D004339:Drug Compounding / Q000379:methods; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry*; D005240:Feasibility Studies; D005990:Glycerol / Q000031:analogs & derivatives / Q000737:chemistry; D006813:Humidity; D009682:Magnetic Resonance Spectroscopy; D010782:Photolysis; D011205:Povidone / Q000737:chemistry; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D014212:Tretinoin / Q000008:administration & dosage* / Q000737:chemistry; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry*
D000970:Antineoplastic Agents; D004304:Dosage Forms; D005079:Excipients; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D014212:Tretinoin; C000515:cremophor EL; D011205:Povidone; D005990:Glycerol