Oral dispersible tablets (ODTs) are promising pharmaceutical dosage forms and, theoretically, could be used for many active pharmaceutical ingredients. The development of ODTs by direct compression with rapid disintegration and suitable hardness is a formulation challenge. The hypothesis of the present work is to prepare a single super-disintegrant multifunctional excipient for the production of ODTs. A single multifunctional tablet component was prepared by crosslinking of chitosan-hydrochloride (CS-H) using multivalent anionic salts, such as carbonate, phosphate, and sulfate. An optimized tablet characteristic concerning the disintegration time (DT) and the compaction properties is obtained utilizing the response surface methodology (RSM). The DT and elastic ratio (ER) were used as responses, and two other factors were studied, i.e., concentration of anions (Csa) and compression pressure (Pc). The obtained crosslinked chitosan anionic salt powders were also characterized in terms of chemical interaction, flowability, moisture uptake, water sorption, and release behavior of an incorporated chemically reactive model drug (ibuprofen lysinate). Based on RSM, the optimal concentrations of chitosan phosphate and chitosan sulfate (as %) were 61.14, 60.89, and 64.65, respectively. The optimal compression pressures (in Mpa) of chitosan carbonate, phosphate, and sulfate were 107.02, 110.39, and 100, respectively. Moreover, 0.31, 0.15, and 0.47 (predicted elastic ratio) and 8, 17, and 2 (disintegration time, s) were obtained for chitosan carbonate, phosphate, and sulfate, respectively. The infrared spectroscopy and the differential scanning microscopy studies were used as tools to detect the interaction. Mean dissolution time was 20.5 min for chitosan hydrochloride compared with 6.9–8.52 for chitosan anionic salts, while the dissolution efficiency was 0.54 for chitosan compared with > 0.8 for chitosan anionic salts. Drug release was higher from chitosan anionic salt matrix systems compared with that of chitosan hydrochloride tablets. The RSM was successfully utilized to prepare optimized tablets using chitosan anionic salt as a single oral dispersible tablet excipient. These salts exhibited suitable physico-mechanical properties upon compaction with a concomitant super-disintegration ability. The chemical reactivity of chitosan hydrochloride against negatively charged molecules was dependent upon crosslinking with negatively charged anions as indicated by the release behavior of ibuprofen lysinate from the chitosan anionic salt matrix systems.
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