Evaluation of the microstructure of semicrystalline solid dispersions.
As a result of an increase in the number of emerging therapies with dissolution limited bioavailability, formulation strategies such as solid dispersions that enhance the rate of solubilization are of interest. In this study, the microstructure of solid dispersions prepared with polyethylene glycol (PEG) and four model compounds with different physicochemical properties was evaluated using a variety of experimental techniques. Solid dispersions were prepared by fusion and evaluated using small-angle X-ray scattering (SAXS), powder X-ray diffraction (PXRD), atomic force microscopy (AFM), optical microscopy and differential scanning calorimetry (DSC). SAXS results indicated that aceclofenac and chlorpropamide solid dispersions favored the interlamellar incorporation of the drug in the PEG matrix. Optical microscopy did not show any evidence of interspherulitic accumulation for any of the model compounds. Haloperidol was highly crystalline in the dispersions, whereas evidence of amorphous material was found for the other model compounds. Results indicated that both the crystallization tendency of the drug and its solubility in amorphous regions of PEG played important roles in determining the location (i.e., interlamellar, interfibrillar or interspherulitic regions) and size of the drug domains within the dispersion.
Zhu
Qing
Q
School of Chemical Engineering and Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, Indiana 47907, USA.
Taylor
Lynne S
LS
Harris
Michael T
MT
D002152:Calorimetry, Differential Scanning; D002747:Chlorpropamide / Q000737:chemistry; D004008:Diclofenac / Q000031:analogs & derivatives / Q000737:chemistry; D005079:Excipients / Q000737:chemistry; D006220:Haloperidol / Q000737:chemistry; D018625:Microscopy, Atomic Force; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D053838:Scattering, Small Angle; D012995:Solubility; D014961:X-Ray Diffraction
D005079:Excipients; D004364:Pharmaceutical Preparations; D004008:Diclofenac; D011092:Polyethylene Glycols; D006220:Haloperidol; C056498:aceclofenac; D002747:Chlorpropamide