Effects of spray drying process parameters on the solubility behavior and physical stability of solid dispersions prepared using a laboratory-scale spray dryer.
OBJECTIVE
The purpose of this study is to determine the process parameters of the laboratory-scale spray dryer affecting the solubility behavior and physical stability of solid dispersions.


METHODS
Solid dispersions of the model drug (nilvadipine or nifedipine) and hypromellose (HPMC) (w/w: 1/1) were prepared using the laboratory-scale spray dryer. As process parameters, nitrogen flow rate, sample concentration and pump speed were investigated. The samples were characterized by dissolution tests, powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), scanning electron microscope (SEM), and nanoscale thermal analysis (Nano-TA). The physical stability was monitored after 7 months storage at 25°C.


RESULTS
Solubility behavior and physical stability were improved by setting the low nitrogen flow rate and high sample concentration. DSC showed that the physical state depends on the spray drying conditions, whereas, every sample showed the similar morphology from SEM results. The difference of solubility behavior and physical stability were found to come from the microstructural phase separation of the spray dried particles using a novel analytical technique (Nano-TA).


CONCLUSIONS
This study demonstrated that nitrogen flow rate and sample concentration should be the critical parameters for the enhancements of the solubility and physical stability of solid dispersions.
Production Engineering Department, Chugai Pharmaceutical Co., Ltd., Kita-ku, Tokyo, Japan. kojimayuk@chugai-pharm.co.jp
Yuki
Y
Kojima
Tomoaki
T
Ohta
Kouji
K
Shiraki
Ryusuke
R
Takano
Hiroyuki
H
Maeda
Yutaka
Y
Ogawa
D002121:Calcium Channel Blockers / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D004339:Drug Compounding; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry*; D006358:Hot Temperature / Q000009:adverse effects; D065347:Hypromellose Derivatives; D007700:Kinetics; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D008956:Models, Chemical; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000737:chemistry*; D033362:Powder Diffraction; D011208:Powders; D011786:Quality Control; D012995:Solubility; D013535:Suspensions; D044366:Transition Temperature
D002121:Calcium Channel Blockers; D005079:Excipients; D011208:Powders; D013535:Suspensions; C035100:nilvadipine; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D009543:Nifedipine