title: The influence of thermal treatment and type of insoluble poly(meth)acrylates on dissolution behavior of very soluble drug from hypromellose matrix tablets evaluated by multivariate data analysis.
abstract: Hypromellose matrices exhibit extended burst effect immediately after contact with aqueous medium, especially when a water-soluble drug is incorporated. The objective of this study was to reduce burst effect and maintain complete dissolution of a very soluble levetiracetam over 12 h period from hypromellose K4M matrices to obtain zero-order kinetics. Desired changes were achieved by applying water dispersions of insoluble Eudragits®(NE, NM, RL, RS) as a granulation liquid to the drug/microcrystalline cellulose mixture during high-shear granulation (non-thermal treated set) and consequently by thermally treating granules or final tablets (TT), respectively. Applying Eudragit®water dispersions to the drug/microcrystalline cellulose mixture was recognized as an effective method of significantly reducing the burst release (25.4-33.7%) of levetiracetam in comparison with a reference sample without Eudragit®. Multivariate data analysis showed that the addition of Eudragit®reduced burst effect, increased fitting with zero-order kinetics, and supported matrix erosion as the supplementary mechanism to predominant diffusion. Moreover, resulting PCA sub-model revealed the addition of Eudragit®RL and thermal treatment of tablets to be the most suitable method of all. For a 12 h dissolution profile, characterized by low burst effect and drug release close to 100% at the 12th hour, sample RL_TT was the most suitable.
authors.affiliation: a Department of Pharmaceutics, Faculty of Pharmacy , University of Veterinary and Pharmaceutical Sciences Brno , Brno , Czech Republic.
authors.forename: Katerina
authors.initials: K
authors.lastname: Kubova
authors.affiliation: a Department of Pharmaceutics, Faculty of Pharmacy , University of Veterinary and Pharmaceutical Sciences Brno , Brno , Czech Republic.
authors.forename: Daniel
authors.initials: D
authors.lastname: Peček
authors.affiliation: a Department of Pharmaceutics, Faculty of Pharmacy , University of Veterinary and Pharmaceutical Sciences Brno , Brno , Czech Republic.
authors.forename: Kristýna
authors.initials: K
authors.lastname: Hasserová
authors.affiliation: a Department of Pharmaceutics, Faculty of Pharmacy , University of Veterinary and Pharmaceutical Sciences Brno , Brno , Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Doležel
authors.affiliation: a Department of Pharmaceutics, Faculty of Pharmacy , University of Veterinary and Pharmaceutical Sciences Brno , Brno , Czech Republic.
authors.forename: Miroslava
authors.initials: M
authors.lastname: Pavelková
authors.affiliation: a Department of Pharmaceutics, Faculty of Pharmacy , University of Veterinary and Pharmaceutical Sciences Brno , Brno , Czech Republic.
authors.forename: Jakub
authors.initials: J
authors.lastname: Vyslouzil
authors.affiliation: a Department of Pharmaceutics, Faculty of Pharmacy , University of Veterinary and Pharmaceutical Sciences Brno , Brno , Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Muselík
authors.affiliation: a Department of Pharmaceutics, Faculty of Pharmacy , University of Veterinary and Pharmaceutical Sciences Brno , Brno , Czech Republic.
authors.forename: David
authors.initials: D
authors.lastname: Vetchy
mesh_terms: D000927:Anticonvulsants / Q000008:administration & dosage* / Q000737:chemistry; D002482:Cellulose / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods; D065546:Drug Liberation; D065347:Hypromellose Derivatives / Q000737:chemistry*; D000077287:Levetiracetam; D015999:Multivariate Analysis; D010889:Piracetam / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry*; D012995:Solubility; D013607:Tablets; D013696:Temperature
chemical_list: D000927:Anticonvulsants; D003692:Delayed-Action Preparations; D011109:Polymethacrylic Acids; D013607:Tablets; C038300:methylmethacrylate-methacrylic acid copolymer; D065347:Hypromellose Derivatives; D000077287:Levetiracetam; D002482:Cellulose; C109691:microcrystalline cellulose; D010889:Piracetam
keywords: Eudragit® NE; HPMC; NM; Prolonged drug release; RL; RS; burst effect; levetiracetam; matrix tablets; multivariate data analysis; thermal treatment