Development of a Direct Compression Excipient from Epichlorohydrin-Crosslinked Carboxymethyl Rice Starch with Sodium Silicate Using a Coprocessing Technique

A new, free-flowing tablet disintegrant based on a coprocessed, cross-linked carboxymethyl rice starch (CXO) is developed using a combination of chemical and physical modifications. Cross-linked carboxymethyl starches are synthesized from an etherification between native rice starch and mono-chloroacetic acid and a cross-linking reaction with epichlorohydrin with various ratios of the etherification reaction time to the cross-linking reaction time (1:1, 1:0.67, and 1:0.33). The modified starches are then coprecipitated with 0-25% sodium silicate solution in methanolic solvent to obtain the CXOs. The physicochemical properties of the CXOs are characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffractometry, and differential scanning calorimetry. The solubility, swellability, moisture sorption capacity, and flowability parameters are also investigated and compared with those of native starch. A 10% sodium silicate solution is found to be best suited for coprocessing, yielding a modified starch (CXO-12) with excellent flowability and compressibility. The lubricant sensitivity ratio of CXO (0.13) is 4-6 times lower than those of sodium starch glycolate (SSG) and croscarmellose sodium (CCS), and its dilution potential (11.2% w/w) is the best among the three excipients. The disintegration times of the model drug tablets containing CXO (16.83 +/- 3.19 s) are not significantly different from those containing SSG (14.00 +/- 2.45 s) or CCS (14.00 +/- 2.83 s). A dissolution study showed that the drug release is greater than 80% after 15 min in the medium. These results suggest that CXO could be applied as a free-flowing super disintegrant for direct compression processes.