Porous soluble dialdehyde cellulose beads: A new carrier for the formulation of poorly water-soluble drugs

Cellulose beads are porous spherical particles with promising futures for drug delivery applications. In this study, novel dialdehyde cellulose (DAC) beads are developed by periodate oxidation of pristine cellulose for oral delivery of weakly basic poorly water-soluble drugs. Diazepam and itraconazole were studied as model drugs. Drug loadings in DAC beads up to 40% were obtained. Depending on the drug loading, complete or partial amorphization of drugs in DAC beads was observed. Drugs in the amorphous state not only presented a higher extent of dissolution from the DAC beads compared to the crystalline model drug, but the obtained concentration was also supersaturated. This supersaturation is attributed to the amorphization of the drugs in the beads in conjunction with the dissolution of the DAC beads at a neutral pH of the dissolution medium. Further, the effects of two different solvent systems used in the lyophilization step during the preparation of the DAC beads (100% water and 90/10% tert-butanol/water mixture) on their structure were investigated. Interestingly, the selection of the solvent system greatly impacted the bead structure, resulting in radically different drug loading capacity, physical properties, and release behavior of the model drugs. In summary, this is the first study that reports on exploiting soluble, porous, dialdehyde cellulose beads, showing great potential as a carrier for improving the rate and extent of dissolution of poorly soluble drugs and maintaining supersaturation.

International Journal of Pharmaceutics Volume 615, 5 March 2022, 121491

https://doi.org/10.1016/j.ijpharm.2022.121491

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