title: Carboxymethyl starch and lecithin complex as matrix for targeted drug delivery: I. Monolithic mesalamine forms for colon delivery.
abstract: For drugs expected to act locally in the colon, and for successful treatment, a delivery device is necessary, in order to limit the systemic absorption which decreases effectiveness and causes important side effects. Various delayed release systems are currently commercialized; most of them based on pH-dependent release which is sensitive to gastrointestinal pH variation. This study proposes a novel excipient for colon delivery. This new preparation consists in the complexation between carboxymethyl starch (CMS) and Lecithin (L). As opposed to existing excipients, the new complex is pH-independent, inexpensive, and easy to manufacture and allows a high drug loading. FTIR, X-ray, and SEM structural analysis all support the hypothesis of the formation of a complex. By minor variation of the excipient content within the tablet, it is possible to modulate the release time and delivery at specific sites of the gastrointestinal tract. This study opens the door to a new pH-independent delivery system for mesalamine targeted administration. Our novel formulation fits well with the posology of mesalamine, used in the treatment of Inflammatory Bowel Disease (IBD), which requires repeated administrations (1g orally four times a day) to maintain a good quality of life.
authors.affiliation: Departement of Chemistry, Université du Québec à Montréal, Montréal, Canada.
authors.forename: Maria
authors.initials: M
authors.lastname: Mihaela Friciu
authors.forename: Tien
authors.initials: T
authors.lastname: Canh Le
authors.forename: Pompilia
authors.initials: P
authors.lastname: Ispas-Szabo
authors.forename: Mircea Alexandru
authors.initials: MA
authors.lastname: Mateescu
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics; D003106:Colon / Q000378:metabolism; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D054709:Lecithins / Q000737:chemistry*; D019804:Mesalamine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D017550:Spectroscopy, Fourier Transform Infrared; D013213:Starch / Q000031:analogs & derivatives* / Q000737:chemistry; D013607:Tablets; D013997:Time Factors; D014961:X-Ray Diffraction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005079:Excipients; D054709:Lecithins; D013607:Tablets; D019804:Mesalamine; D013213:Starch; C034848:carboxymethyl starch
keywords: CMC; CMC/L; CMS; CMS/GT; CMS/L; Carboxymethyl starch; Colon delivery; Complex; FTIR; Fourier transform infrared spectroscopy; GI; GT; High drug loading; IBD; L; Lecithin; Mesalamine; SEM; SGF; SIF; X-ray diffractometry; XRD; carboxymethyl starch; carboxymethyl starch/glyceryl tristearate; carboxymethyl starch/lecithin complex; carboxymethylcellulose; carboxymethylcellulose/lecithin; gastrointestinal; glyceryl tristearate; inflammatory bowel disease; lecithin; scanning electron microscopy; simulated gastric fluid; simulated intestinal fluid