In vitro and in vivo evaluation of carbamazepine-loaded enteric microparticles

The objective of the study was to prepare and evaluate carbamazepine-loaded enteric microparticles produced by a novel coacervation method. An aqueous polymeric stabilizer solution was added to an organic carbamazepine/Eudragit ® L100-55 solution. Water, which is a non-solvent for the drug and the e...

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Bibliographic Details
Published in:International journal of pharmaceutics 2007-02, Vol.331 (1), p.84-92
Main Authors: Dong, W.Y., Maincent, P., Bodmeier, R.
Format: Article
Language:English
Subjects:
Acrylic Resins - chemistry
Animals
Anticonvulsants - blood
Anticonvulsants - chemistry
Anticonvulsants - pharmacokinetics
Biological and medical sciences
Biological Availability
Carbamazepine
Carbamazepine - blood
Carbamazepine - chemistry
Carbamazepine - pharmacokinetics
Coacervation
Dissolution rate
Drug Carriers - chemistry
Drug Carriers - pharmacokinetics
Drug Stability
Enteric polymer
General pharmacology
Male
Medical sciences
Microencapsulation
Microscopy, Electron, Scanning
Particle Size
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Rabbits
Solubility
X-Ray Diffraction
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Summary:The objective of the study was to prepare and evaluate carbamazepine-loaded enteric microparticles produced by a novel coacervation method. An aqueous polymeric stabilizer solution was added to an organic carbamazepine/Eudragit ® L100-55 solution. Water, which is a non-solvent for the drug and the enteric polymer, caused phase separation and the formation of coacervate droplets. These droplets hardened into microparticles upon further addition of the aqueous phase. The microparticles were characterized with respect to particle size distribution, morphology, encapsulation efficiency, yield, physical state and physical stability of the drug, wettability, in vitro release and in vivo bioavailability. Microparticles with a smooth surface and dense structure were obtained with high encapsulation efficiency (>85%) and yield (>90%). The drug was in a non-crystalline state in the matrix and physically stable for 5 months at room temperature. Under sink conditions, the drug dissolution rate from the microparticles was significantly enhanced compared to the physical mixture and to the pure drug; the release profile of the microparticles was stable after 5 months. Under non-sink conditions, an unstable supersaturated solution of carbamazepine was obtained from microparticles with the subesequent formation of needle-shaped crystals. The high surface area and good wettability of the microparticles, the non-crystalline state of the drug in the matrix and the fast dissolution rate contributed to a significantly enhanced oral bioavailability from the microparticles when compared to the physical mixture.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2006.09.018