title: Mechanochemical solid-state polymerization (XI): effect of water-insoluble pharmaceutical aids on drug release from mechanically synthesized polymeric prodrugs.
abstract: We discuss here the effect of water-insoluble pharmaceutical aids on the nature of drug release from composite polymeric prodrugs synthesized by mechanochemical solid-state polymerization. Magnesium stearate (Mgst) and hydrogen castor oil (HCO) were used as water-insoluble pharmaceutical aids. Composite polymeric prodrugs were synthesized by the mechanochemical solid-state polymerization of a vinyl monomer of 5-fluorouracil (I) in the presence of Mgst or HCO. The molecular weight of the resulting polymeric prodrugs increased with increasing the content of Mgst or HCO. Prodrug hydrolysis was carried out in a heterogeneous system in phosphate buffer at pH 6.8 and 37 degrees C. The rate of drug release from the composite polymeric prodrug containing Mgst (Poly-Mgst) was faster than that from polymeric prodrug containing no pharmaceutical aids (Poly-Non), while hydrolysis of the composite polymeric prodrug containing HCO (Poly-HCO) was slower than Poly-Non. Scanning electron microscope (SEM) photos showed the surface of Poly-HCO was smoother than that of Poly-Non and Poly-Mgst. It was suggested that the slower drug release from Poly-HCO may be responsible for the smaller specific surface area than that of Poly-Non. It was also shown that the rate of drug release from the composite polymeric prodrugs decreases with increasing the content of Mgst or HCO. Hence, novel composite polymeric prodrugs with a variety of drug release rates can be prepared by mechanochemical solid-state polymerization in a totally dry process.
authors.affiliation: Laboratory of Pharmaceutical Physical Chemistry, Gifu Pharmaceutical University, 5-6-1 Mitahora-Higashi, Gifu 502-8585, Japan. skondo@gifu-pu.ac.jp
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Kondo
authors.forename: Shouichi
authors.initials: S
authors.lastname: Hosaka
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sasai
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kuzuya
mesh_terms: D010592:Pharmaceutic Aids / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011108:Polymers / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011355:Prodrugs / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D012995:Solubility / Q000187:drug effects; D013678:Technology, Pharmaceutical / Q000379:methods*; D014867:Water / Q000737:chemistry / Q000378:metabolism
chemical_list: D010592:Pharmaceutic Aids; D011108:Polymers; D011355:Prodrugs; D014867:Water