title: Controlled release floating multiparticulates of metoprolol succinate by hot melt extrusion.
abstract: We present hot melt extrusion (HME) for the design of floating multiparticulates. Metoprolol succinate was selected as the model drug. Our foremost objective was to optimize the components Eudragit(®) RS PO, polyethylene oxide (PEO) and hydroxypropyl methylcellulose (HPMC) to balance both buoyancy and controlled release. Gas generated by sodium bicarbonate in acidic medium was trapped in the polymer matrix to enable floating. Eudragit(®) RS PO and PEO with sodium bicarbonate resulted in multiparticulates which exhibited rapid flotation within 3 min but inadequate total floating time (TFT) of 3h. Addition of HPMC to the matrix did not affect floating lag time (FLT), moreover TFT increased to more than 12h with controlled release of metoprolol succinate. Floating multiparticulates exhibited t50% of 5.24h and t90% of 10.12h. XRD and DSC analysis revealed crystalline state of drug while FTIR suggested nonexistence of chemical interaction between the drug and the other excipients. The assay, FLT, TFT and the drug release of the multiparticulates were unchanged when stored at 40°C/75%RH for 3 months confirming stability. We present floating multiparticulates by HME which could be extrapolated to a range of other drugs. Our approach hence presents platform technology for floating multiparticulates.
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga (E), Mumbai 400019, Maharashtra, India.
authors.forename: Vilas N
authors.initials: VN
authors.lastname: Malode
authors.affiliation: Centre for Pharmaceutical Engineering Sciences, University of Bradford, Richmond Road, Bradford, Yorkshire BD7 1DP, United Kingdom.
authors.forename: Anant
authors.initials: A
authors.lastname: Paradkar
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga (E), Mumbai 400019, Maharashtra, India. Electronic address: pvdevarajan@gmail.com.
authors.forename: Padma V
authors.initials: PV
authors.lastname: Devarajan
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D004355:Drug Stability; D005079:Excipients; D006358:Hot Temperature; D065347:Hypromellose Derivatives; D007700:Kinetics; D008790:Metoprolol / Q000008:administration & dosage* / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols; D011109:Polymethacrylic Acids
chemical_list: D000319:Adrenergic beta-Antagonists; D003692:Delayed-Action Preparations; D005079:Excipients; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols; D008790:Metoprolol
keywords: Eudragit(®) RS PO; Floating multiparticulates; Glyceryl monostearate (PubChem CID: 24699); Hot melt extrusion; Hydrochloric acid (PubChem CID: 313); Metoprolol succinate; Metoprolol succinate (PubChem CID: 4171); Polyethylene oxide; Sodium bicarbonate; Sodium bicarbonate (PubChem CID: 516892)