title: Characterization and stability of ternary solid dispersions with PVP and PHPMA.
abstract: The effect of adding a third polymer to immiscible binary solid dispersions was investigated. The model actives griseofulvin (GF), progesterone (PG) and phenindione (PD) were selected because they exemplify a key property of many poorly soluble molecules of having at least one hydrogen bonding acceptor moiety while not having any hydrogen bond donating moieties. Ternary solid dispersions of the drug, PVP (polyvinylpyrrolidone) (proton acceptor) and PHPMA (poly[2-hydroxypropyl methacrylate]) (proton acceptor and donor) were prepared by spray drying. Stability results showed that binary solid dispersions (API and PVP) of GF and PVP crystallized quickly while the amorphous form was not possible to prepare for PG and PD. The amorphous form was prolonged upon the incorporation of PHPMA in the solid dispersion (API, PHPMA and PVP). Based on measuring the melting points, the energy of mixing the drug with the polymer was calculated using the Flory-Huggins theory. The results showed that GF had the lowest free energy followed by PG and finally PD which agreed well with the stability results. These results suggest that the addition of a third polymer to immiscible binary solid dispersions can significantly improve the stability of the amorphous form.
authors.affiliation: Institute of Pharmaceutical Sciences, King's College London, Franklin Wilkins Building, 150 Stamford Street, London SE1 9NH, UK. hisham.al-obaidi@kcl.ac.uk
authors.forename: Hisham
authors.initials: H
authors.lastname: Al-Obaidi
authors.forename: Peng
authors.initials: P
authors.lastname: Ke
authors.forename: Steve
authors.initials: S
authors.lastname: Brocchini
authors.forename: Graham
authors.initials: G
authors.lastname: Buckton
mesh_terms: D003460:Crystallization; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D006118:Griseofulvin / Q000008:administration & dosage* / Q000737:chemistry; D006860:Hydrogen Bonding; D010630:Phenindione / Q000008:administration & dosage* / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D011374:Progesterone / Q000008:administration & dosage* / Q000737:chemistry; D012995:Solubility; D044366:Transition Temperature
chemical_list: D004337:Drug Carriers; D011109:Polymethacrylic Acids; D006118:Griseofulvin; C011533:Duxon; D011374:Progesterone; D010630:Phenindione; D011205:Povidone