The influence of magnesium stearate on the characteristics of mucoadhesive microspheres.
Microspheres containing the mucoadhesive polymer chitosan hydrochloride, with matrix polymer Eudragit RS, pipemidic acid as a model drug and agglomeration preventing agent magnesium stearate were prepared by the solvent evaporation method. The amount of magnesium stearate was varied and the following methods were used for microsphere evaluation: sieve analysis, drug content and dissolution determination, scanning electron microscopy, x-ray diffractometry, DSC and FTIR spectroscopy. The results showed that average particle size decreased with increasing amount of magnesium stearate used for microsphere preparation. This is probably a consequence of stabilization of the emulsion droplets with magnesium stearate. Higher pipemidic acid content in the microspheres was observed in larger particle size fractions and when higher amounts of magnesium stearate were used. It was also found that these two parameters significantly influenced the dissolution rate. The important reason for the differences in drug content in microspheres of different particle sizes is the diffusion of pipemidic acid from the acetone droplets in liquid paraffin during the preparation procedure. The physical state of pipemidic acid changed from crystalline to mostly amorphous with its incorporation in microspheres, as shown by x-ray diffractometry and differential scanning calorimetry. No differences were observed in the physical state of pipemidic acid and in microsphere shape and surface between different size fractions of microspheres, prepared with different amounts of magnesium stearate. Additionally, no correlation between the physical state of the drug in different microspheres and their biopharmaceutical properties was found.
Bogataj
M
M
Faculty of Pharmacy, University of Ljubljana, Slovenia. marija.bogataj@ffa.uni-lj.si
Mrhar
A
A
Grabnar
I
I
Rajtman
Z
Z
Bukovec
P
P
Srcic
S
S
Urleb
U
U
D000180:Acrylic Resins; D000268:Adhesiveness; D002152:Calorimetry, Differential Scanning; D002214:Capsules; D002686:Chitin / Q000031:analogs & derivatives; D048271:Chitosan; D004339:Drug Compounding; D016503:Drug Delivery Systems; D006801:Humans; D066298:In Vitro Techniques; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D009092:Mucous Membrane; D010316:Particle Size; D010876:Pipemidic Acid / Q000008:administration & dosage; D013229:Stearic Acids; D014961:X-Ray Diffraction
D000180:Acrylic Resins; D002214:Capsules; D013229:Stearic Acids; D002686:Chitin; C050528:Eudragit RS; C031183:stearic acid; D048271:Chitosan; D010876:Pipemidic Acid