Development of cyclodextrin microspheres for pulmonary drug delivery.
OBJECTIVE
Microparticles of diameter < 5 microm were synthesized by interfacial cross-linking of 7.5% (w/v) beta-cyclodextrins (beta-CD) with 4.5% (w/v) terephtaloyle chloride in 1 M NaOH, in order to provide stable vector for drug encapsulation suitable for administration at the alveolar scale.


METHODS
Batches were prepared varying different parameters such as amount of monomer (beta-CD) (5-30% w/v), NaOH concentration (0.5-4 M), reaction time (15-240 min), agitation rate (8000-24000 rpm), amount of cross-linking agent (terephtaloyle chloride: 1.25-10% w/v), surfactant percentage (2.5-10% of Span 85), studying the influence of the freeze-drying step. Microparticles were controlled with respect to their size by a laser diffraction technique, pH of the colloidal suspension, IR spectroscopy, Differential Scanning Calorimetry. After optimization of the microparticles size, complexation with amikacin sulfate was investigated comparing encapsulation efficiency and yield at each step of the preparation (solubilization, emulsification, cross-linking, freeze-drying), contact time and influence of the amount of amikacin.


RESULTS
An optimized method was obtained with 1 M NaOH, 4.5% (w/v) cross-linking agent and 5% (w/v) surfactant agent, a 30 min reaction time, a 24000 rpm agitation rate, conducting to microparticles whose size is inferior to 5 microm. Amikacin sulfate encapsulation in polycondensed beta-cyclodextrin showed that better incorporation was obtained during the solubilization step or just before freeze-drying.


CONCLUSIONS
Amikacin encapsulation in 5 microm diameter microparticles of beta-CD is achievable for pulmonary drug delivery.
Skiba
Malika
M
Laboratoire de Pharmacie Galénique et Biopharmacie, ADEN-UPRES EA 3234, UFR de Medecine-Pharmacie, Rouen Cedex, France.
Bounoure
Frédéric
F
Barbot
Cecile
C
Arnaud
Philippe
P
Skiba
Mohamed
M
D000280:Administration, Inhalation; D003505:Cyclodextrins / Q000008:administration & dosage / Q000138:chemical synthesis*; D016503:Drug Delivery Systems / Q000379:methods*; D008168:Lung / Q000187:drug effects; D008863:Microspheres; D010316:Particle Size
D003505:Cyclodextrins