title: Micropellet-loaded rods with dose-independent sustained release properties for individual dosing via the Solid Dosage Pen.
abstract: Individual dosing of medicines is relevant for paediatrics, geriatrics and personalised medicine. The Solid Dosage Pen (SDP) allows for individual dosing by cutting monolithic, tablet-like drug carriers of pre-defined heights. The aim of the present study was to develop micropellet-loaded rods (MPLRs) with dose-independent sustained release properties for individual dosing via the Solid Dosage Pen. Therefore, micropellets were successfully layered with carbamazepine and coated with polyvinyl acetate (PVAc) and PVAc/polyvinyl alcohol-polyethylene glycol (PVA-PEG). The tensile strength of the sustained release micropellets (300-450 μm) was more than two times higher (12.6-17.1 MPa) than pressures occurring during ram-extrusion of the MPLRs (below 5.8 MPa). Due to relative crystallinities above 93% for PVAc and PVA-PEG a low solubility of the coating films within the PEG-matrix was observed. The sustained release micropellets were successfully incorporated into MPLRs. Drug release properties of the pellets maintained after embedding into the matrix. Hence, the MPLRs provided dose-independent prolonged drug liberation which was not achieved for drug-loaded rods before. The MPLRs permitted the application of the SDP with a precise drug delivery from individually cut single doses. Storage stability was proven for MPLRs containing PVAc/PVA-PEG coated pellets. In conclusion, the MPLRs combined the advantages of multiparticulate dosage forms with the SDP as a device for individual dosing.
authors.affiliation: Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Duesseldorf, Germany.
authors.forename: Eva Julia
authors.initials: EJ
authors.lastname: Laukamp
authors.affiliation: Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Duesseldorf, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Knop
authors.affiliation: Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Duesseldorf, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Thommes
authors.affiliation: Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Duesseldorf, Germany. Electronic address: Joerg.Breitkreutz@hhu.de.
authors.forename: Joerg
authors.initials: J
authors.lastname: Breitkreutz
mesh_terms: D000927:Anticonvulsants / Q000008:administration & dosage / Q000737:chemistry; D002220:Carbamazepine / Q000008:administration & dosage* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003460:Crystallization; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004355:Drug Stability; D004356:Drug Storage; D011092:Polyethylene Glycols; D011142:Polyvinyl Alcohol / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry; D012995:Solubility; D013718:Tensile Strength
chemical_list: D000927:Anticonvulsants; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011145:Polyvinyls; C013215:polyvinyl acetate; D002220:Carbamazepine; D011092:Polyethylene Glycols; D011142:Polyvinyl Alcohol
keywords: Individual dosing; Micropellets; Multiparticulate dosage form; Solid Dosage Pen; Sustained release