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Carboxymethyl Starch Excipients for Drug Chronodelivery

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Abstract

Carboxymethyl starch (CMS) is a pH-responsive excipient exhibiting also interesting properties for applications in delayed drug delivery systems. This work was aimed to investigate the release properties of monolithic and dry-coated tablets based on ionic sodium CMS and on protonated CMS, formulated with three model tracers: acetaminophen, acetylsalicylic acid (ASA), and sodium diclofenac. The sodium or protonated CMS were obtained from the same CMS synthesis by controlling the final pH of reaction media. The two forms of CMS were confirmed by the Fourier transform infrared spectroscopy. The in vitro dissolution profiles for monolithic and double core tablets were different and allowed a better understanding of characteristics of the two excipient forms. It was found that the protonated CMS exhibited a better stability in simulated gastric fluid in comparison to its sodium salt in monolithic dosage forms, whereas both excipients afforded a complete gastric protection of drugs when formulated as dry-coated dosages. Determination of water uptake and erosion rate of monolithic matrices based on the two CMS forms showed different mechanisms involved in the delivery of the three model active molecules in simulated intestinal media. When pancreatic enzymes were added in dissolution media, the drug release was accelerated showing that CMS is still a substrate for alpha-amylase. Both sodium and protonated starch excipients, formulated as dry-coated dosages, afforded a good gastro-protection and allowed a drug chronodelivery at various intervals up to 4–5 h. They could be considered as an alternative for delayed delivery and a solvent-free coating procedure.

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Acknowledgments

Thanks are due to NSERC of Canada for the financial support of this research (MAM) and for a Canada fellowship for doctoral studies (CC).

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Authors and Affiliations

  1. Department of Chemistry and PharmaQAM Center, Université du Québec à Montréal, CP 8888, Branch. A, Montreal, Quebec, H3C 3P8, Canada

    Pompilia Ispas-Szabo, Patrick De Koninck, Carmen Calinescu & Mircea Alexandru Mateescu

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  1. Pompilia Ispas-Szabo
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  2. Patrick De Koninck
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  3. Carmen Calinescu
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  4. Mircea Alexandru Mateescu
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Correspondence to Mircea Alexandru Mateescu.

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Ispas-Szabo, P., De Koninck, P., Calinescu, C. et al. Carboxymethyl Starch Excipients for Drug Chronodelivery. AAPS PharmSciTech 18, 1673–1682 (2017). https://doi.org/10.1208/s12249-016-0634-8

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  • DOI: https://doi.org/10.1208/s12249-016-0634-8

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