Enhanced release of indomethacin from Pvp/stearic acid microcapsules prepared coupling Co-freeze-drying and ultrasound assisted spray-congealing process.
OBJECTIVE
Fast releasing indomethacin microparticles were prepared encapsulating co-freeze-dried indomethacin/poly(vinylpyrrolidone) particles (IMC/PVP) into molten stearic acid (SA), by means of a ultrasonic spray-congealing technique.


METHODS
IMC particles were suspended in a PVP aqueous solution and the system was then freeze-dried. A suspension was prepared from the co-freeze dried IMC/PVP powder into molten SA that was then atomized into small droplets using ultrasound. Solidification in air produced microparticles having regular macroscopic morphology and coated by a SA thin external film. At each step the material was examined by electron microscopy (SEM and EDAX), thermal analysis and dissolution tests.


RESULTS
SEM examination did not reveal a smooth surface, differently from what was observed in the case of pure SA microparticles, obtained by the same method. The external film was found to uniformly protect the internal core of the capsules: EDAX spectra demonstrated the absence of the IMC identifying Cl peak on the surface, when the spectra were carried out at low energy of the electron beam. HPLC analysis verified that the drug was uniformly distributed inside the final microparticles at all the size fractions considered. Thermal microscopy confirmed the presence of IMC crystals, after the fusion of the external SA coat.


CONCLUSIONS
The behavior of microparticles to dissolution at pH 7.4 was superior to that of pure drug, reaching 70% of the drug released, after 20 min. Finally the system examined is stable towards aging: no difference in the dissolution behavior could be detected for the final microparticles after 8 months at 25 degrees C.
Cavallari
Cristina
C
Departimento di Scienze Farmaceutiche, Università di Bologna, Via San Donato 19/2, Bologna 40127, Italy. cavallar@biocfarm.unibo.it
Luppi
Barbara
B
Di Pietra
Anna Maria
AM
Rodriguez
Lorenzo
L
Fini
Adamo
A
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000493:pharmacokinetics; D002152:Calorimetry, Differential Scanning; D002214:Capsules; D002851:Chromatography, High Pressure Liquid; D003116:Color; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics*; D004339:Drug Compounding / Q000379:methods; D005612:Freeze Drying / Q000379:methods*; D007213:Indomethacin / Q000737:chemistry / Q000493:pharmacokinetics*; D008854:Microscopy, Electron; D010316:Particle Size; D011145:Polyvinyls / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry*; D012995:Solubility; D013229:Stearic Acids / Q000737:chemistry*; D013535:Suspensions; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature; D013997:Time Factors; D014465:Ultrasonics; D014961:X-Ray Diffraction
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002214:Capsules; D003692:Delayed-Action Preparations; D011145:Polyvinyls; D011759:Pyrrolidines; D013229:Stearic Acids; D013535:Suspensions; C505150:poly(N-vinylpyrrolidine); C031183:stearic acid; D007213:Indomethacin