Marie-Christine Levy

Cross-linked β-cyclodextrin microcapsules : preparation and properties

Abstract Microcapsules were prepared by interfacial cross-linking of β-cyclodextrins (β-CD) with terephthaloyl chloride (TC). Batches were prepared from β-CD solutions in 1 M NaOH, using 5% TC and a 30 min reaction time. Microcapsules were studied with respect to morphology (microscopy), size (laser diffraction technique) and, for selected batches, IR spectroscopy, determination of β-CD content (polarimetry after alkaline dissolution of microcapsules) and complexing properties, evaluated using p -nitrophenol (pNP) as the guest molecule. Well-formed microcapsules were obtained from 5, 7.5, and 10% β-CD solutions. The mean size of all batches was in the 10–35 μm range. The IR spectrum showed bands at 1724, 1280 and 731 cm −1 , reflecting the formation of esters. The β-CD contents were 46, 56–58 or 60–66% for batches prepared from 5, 7.5 or 10% β-CD solutions, respectively. The experiments conducted with 1 mM pNP showed a rapid complexation reaching a maximum within 1 h. When incubating 50 mg lyophilized microcapsules in 10 ml pNP solution, the maximal fixation (97.8 μmol/g microcapsules) was observed for small-sized particles (≈11 μm) prepared from a 7.5% β-CD solution. The method then appears as a simple and rapid procedure to provide stable microcapsules, having an interesting guest-binding ability.

Cross-linked β-cyclodextrin microcapsules. II. Retarding effect on drug release through semi-permeable membranes

Microcapsules were prepared by interfacial cross-linking of beta-cyclodextrins (beta-CD) with terephthaloylchloride (TC) as described previously. Complexation assays were conducted with propranolol HCl. After 1 h incubation of 50 mg lyophilized microcapsules in 10 ml propranolol solution, the amounts of fixed drug were 507.5+/-8.6 micromol and 811.2+/-16.0 micromol per g lyophilized microcapsules with 1 mM and 2 mM solutions, respectively. A dialysis experiment was then performed. After 1 h incubation of microcapsules (10 or 50 mg) in 10 ml of 2 mM propranolol solution, the suspension was dialysed against a phosphate buffer pH 7.4 at 37 degrees C. The drug diffusion was all the more retarded that the amount of added beta-CD microcapsules was higher. Finally, double microcapsules were prepared using a suspension of beta-CD microcapsules (10-100 mg) in a solution of methylene blue in an acetate buffer pH 7.4. After adding human serum albumin (HSA), the suspension was emulsified in cyclohexane and double microcapsules were obtained by cross-linking the HSA with TC. In vitro release studies showed that the incorporation of beta-CD microcapsules resulted in a decrease in release rate of methylene blue, the decrease being related to the amount of encapsulated beta-CD microcapsules. The study then suggests interesting applications of beta-CD microcapsules for modulating the release rate of drugs through semi-permeable membranes.