Carboxymethyl high amylose starch as excipient for controlled drug release: mechanistic study and the influence of degree of substitution.

Sodium carboxymethyl high amylose starch, CMHAS(Na), with a DS up to 1.74 were synthesized in non-aqueous medium (with yields as high as 72%) in order to investigate the influence of the degree of substitution (DS) on physical and drug release properties. The CMHAS(Na) was converted to protonated form, CMHAS(H), by acid treatment. The DS and conversion of CMHAS(Na) to CMHAS(H) had a major impact on the physical properties of CMHAS particles and resulting tablets. Dissolution tests performed in simulated gastric fluid (SGF, pH 1.2) and in simulated intestinal fluid (SIF, pH 6.8), with acetaminophen as drug model (20% loading) showed CMHAS as a pH sensitive hydrophilic matrix whereas CMHAS(Na) seems suitable as controlled release matrix. CMHAS(Na) with DS between 0.1 and 0.2 can be preferably used as sustained release excipient since in both dissolution media, the drug release was driven by diffusion over a period up to 12 h. CMHAS(Na) with high DS, between 0.9 and 1.2, can be used as delayed release excipient since drug release in SGF was driven by diffusion over a period up to 20 h and in SIF by fast erosion lowering to less than 3 h the complete release of the drug.