The influence of protonation ratio on properties of carboxymethyl starch excipient at various substitution degrees: Structural insights and drug release kinetics

Published Date

15 July 2010, Vol.394(1):75–84, doi:10.1016/j.ijpharm.2010.04.037

Title 

The influence of protonation ratio on properties of carboxymethyl starch excipient at various substitution degrees: Structural insights and drug release kinetics

• Author 

• Elias Assaad
• Mircea Alexandru Mateescu ^,

• Department of Chemistry and Pharmaqam Center, Université du Québec à Montréal (UQAM), CP 8888, Succ. Centre-ville, Montréal (QC), H3C 3P8, Canada

Received 4 March 2010. Revised 22 April 2010. Accepted 26 April 2010. Available online 30 April 2010.

Abstract

Carboxymethyl starch (CMS) with pH sensitivity modulated by the protonation ratio (PR 0–100%) and the degree of substitution (DS 0.07–0.20) was synthesized in aqueous medium. The properties of CMS excipient and the mechanism of acetaminophen release from monolithic tablets in simulated gastric fluid (SGF, pH 1.2) and in simulated intestinal fluid (SIF, pH 6.8) were investigated. Compared to sodium CMS, the protonated CMS provided a longer release time which increases with the increase of PR. Over storage time, the highly protonated CMS showed a decrease in solubility and a progressive structural alteration due to hydrogen bonded carboxyl groups. Simultaneously, an acceleration of release rate of formulated drug was observed. The CMS(DS 0.11) with PR up to 50% showed relatively low sensitivity to dissolution medium pH and sustained release pattern almost independent of tablet preincubation in SGF and of drug loading (20% and 40%). The CMS(DS 0.20) was more sensitive to pH and showed an accelerated release rate in SIF. For the CMS formulations, a diffusion mechanism was suggested in SGF, whereas in SIF the release was mostly controlled by swelling and erosion.

Abbreviations

CMS, carboxymethyl starch

SGF, simulated gastric fluid (pH 1.2)

SIF, simulated intestinal fluid (pH 6.8)

DS, degree of substitution (the average number of carboxymethyl groups per glucose unit)

PR, protonation ratio as percentage of carboxyl groups (–COOH) in the sum of carboxylate (–COONa) and carboxyl groups

S_control, starch treated with NaOH to obtain the control of CMS samples

S_g, gelatinized starch

t_90%, time (h) for the release of 90% of drug.

Keywords

Carboxymethyl starch

Excipient

Protonation ratio

Degree of substitution

Monolithic tablet

Drug delivery

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