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The effectiveness of cyclodextrin polymer as a disintegrating agent for directly compressed tablets containing furosemide, cyclodextrin polymer and microcrystalline cellulose was investigated. Regression analysis based on statistically designed experiments made it possible to determine how various tablet characteristics are affected by the amount of excipients. As a result of computer optimization an optimum formulation was obtained exhibiting high dissolution rate, sufficient dissolution stability, fast disintegration, high hardness immediately after preparation and adequate hardness after ageing.

The binding and disintegrating properties of cyclodextrin polymer as well as its effect on the dissolution of a poorly soluble drug have been evaluated on the basis of the hardness, friability and disintegration time of directly compressed tablets. The hardness of tablets containing cyclodextrin polymer in addition to potato starch or lactose was lower than that of tablets with microcrystalline cellulose indicating that cyclodextrin polymer has a relatively poor binding capacity. The disintegrating action of cyclodextrin polymer was compared to those of potato starch and lactose, with microcrystalline cellulose as a binder. Equal disintegration times were obtained with 2.5% cyclodextrin polymer, 12.5% potato starch, and 25% lactose. The dissolution rate of furosemide was greatly accelerated by as little as 2.5% cyclodextrin polymer added to microcrystalline cellulose. A somewhat lower dissolution rate was observed with 12.5% potato starch. As a result it was shown that cyclodextrin polymer, which has excellent disintegrating properties as well as some binding capacity, can be used advantageously in direct compression systems as a binder-disintegrant.

Clofazimine (CLZ) is an antibiotic with a promising behavior against Gram-positive bacteria; however, the drug is completely insoluble in water and accumulates in fat tissues. We explored nanocarriers, labeled and not labeled with rhodamine, consisting of negatively charged sulfobutylether-beta-cyclodextrins for CLZ loading. A new oligomeric carrier was obtained cross-linking beta CyD with epichlorohydrin followed by sulfonation in a strongly alkaline aqueous medium. The oligomeric carrier has a MW of 53 kDa and forms small nanoparticles of a few tens of nm. With aqueous solutions containing a 25 mg/mL oligomeric carrier, we loaded up to 0.5 mg/mL of drug. The oligomers exhibited a 10-fold better loading capacity compared to monomers and formed nanoparticles with a size in the 20-60 nm range after drug loading. Circular dichroism confirmed encapsulation of the CLZ in the nanocarriers. All carriers with or without CLZ are not cytotoxic up to 1 mu M, while CLZ alone is highly cytotoxic at the same concentration. The drug has IC50 values below 100 nM against S. epidermidis. The same holds true also for clinical isolates of S. epidermidis, some displaying MDR So, the selectivity index significantly increased for CLZ/carrier systems compared to the drug alone. Taken all together, our results open new avenues for the clinical application of this antibiotic.