Carboxymethyl Starch Excipients for Drug Chronodelivery.

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.

Carboxymethyl-starch excipients for gastrointestinal stable oral protein formulations containing protease inhibitors.

PURPOSE: The aim of this study was to develop a formulation for bioactive compounds using Carboxymethyl Starch (CMS) as excipient containing protease inhibitors. This formulation provided gastro protection and enhanced stability against pancreatic enzymes. Such stability is needed for formulation of oral vaccines with specific antigens. METHODS: CMS was synthesized by treatment of starch with monochloroacetic acid in conditions leading to a substitution degree of about 1 meq/g and used as excipient for monolithic devices (300 mg tablets). Pefabloc SC and Aprotinin inhibitors were tested in dissolution media and in formulation to prevent the degradation of released bioactive materials. To evaluate the structural integrity and biological stability of plant proteins in the CMS formulation, albumin and lipase were added to the plant protein extract as protein and respectively as enzyme markers. The amounts of released and recovered proteins were evaluated by SDS-PAGE and densitometric analysis. RESULTS: It was found that 1.6 % (w/w) of Pefabloc SC provides 98 % protection of the released plant proteins for formulations of 30 % alfalfa protein extract (APE) with CMS. In addition, when bovine serum albumin (BSA) added to the plant protein extract as a marker, 90 % protection of the released BSA was observed. Furthermore, a much higher lipase activity was found in the releasing media when the formulations contained Pefabloc SC. CONCLUSION: Formulations with CM-Starch excipients and containing protease inhibitors prevent protein degradation and protect lipase activity, showing a marked potential to use for orally administered bioactive peptides and therapeutic enzymes.