ABSTRACT
This article investigated preparation of solid dispersions containing a poor water-soluble drug, indomethacin (IND), and a new surfactant polymer, polyoxyethylene 32 distearate (POED). Solid dispersions were prepared by the melting method and characterized by DSC, hot-stage microscopy (HSM), X-ray diffraction (XRD) and scanning electron microscopy (SEM). DSC and HSM analyses performed on IND/POED physical mixtures indicated that IND could dissolve in liquid POED. The materials showed complete miscibility at liquid state. Combination of DSC, XRD, and SEM revealed that these materials had limited miscibility at the solid state. Up to 20% w/w IND in POED, we did not detect significant modification of physical properties of the polymer. It supports the formation of a solid solution of IND in solid POED. Above 20% w/w, the solid dispersions presented particular behavior upon heating (recrystallization of IND) and at the solid state (presence of some IND crystallites). Under 3-month storage at 25 degrees C/53% RH, the solid dispersions demonstrated a good stability of the samples. Finally, in vitro dissolution studies showed that IND release was greatly improved (5.5-12 times as fast) by formation of solid dispersion. This enhancement was principally attributed to the high dispersion of IND in POED and to the polymer surfactant properties.
Subject(s)
Drug Carriers/chemistry , Polyethylene Glycols/chemistry , Crystallization , Drug Carriers/administration & dosage , Drug Carriers/chemical synthesis , Drug Compounding/methods , Drug Stability , Drug Storage , Indomethacin/administration & dosage , Indomethacin/chemistry , Polyethylene Glycols/administration & dosage , Polymers/administration & dosage , Polymers/chemistry , Solubility , Surface-Active Agents/administration & dosage , Surface-Active Agents/chemistryABSTRACT
A thorough review of the relevant literature reveals that the interaction between water vapour and magnesium stearate, in contrast to many other metal soaps, is not properly understood. The structural modifications associated with the up-take or loss of water of vegetable-derived commercial magnesium stearate powders exposed to humid air or vacuum at room temperature are investigated using standard powder X-ray diffractometry. It is found that in such conditions magnesium stearate reacts reversibly with the vapour phase with structural consequences very similar to the high temperature transition between the crystalline and rotator phases of other anhydrous metal soaps. When temperature is increased under dry nitrogen the diffraction band characteristic of the rotator phase shifts towards higher angle values and the corresponding lattice spacing increases at the rate of 6.9x10(-4)C(-1). Melting takes place gradually above 100 degrees C as revealed by the collapse of the diffraction band and the growth of the broader diffusion band characteristic of the liquid state. Full clarification of the structure of the hydrated and dried phases proves impossible based on powder diffraction spectra obtained with conventional high resolution X-ray diffraction equipment.
