title: New formulation of in situ gelling Metolose-based liquid suppository.
abstract: BACKGROUND
  An in situ gelling liquid suppository is liquid at room temperature but forms a gel at body temperature. In our work, Metolose® SM-4000 (methylcellulose) is studied that basically shows thermal gelation at 68°C (2%, w/w).
  
  
  OBJECTIVE
  The objective was to study the potency of different factors (concentration, pH, additives) to change the value of thermal gelation temperature (T (t)) for Metolose® to form an in situ gelling liquid suppository.
  
  
  METHODS
  We studied the effect of Metolose® concentration, pH, and salts (sodium chloride, potassium chloride, sodium hydrogen carbonate, and sodium monohydrogen phosphate) on T (t) by viscosimetry. To choose the appropriate compound, in vitro drug release was examined. Rectal safety test was performed on rats in vivo after 12-hour application.
  
  
  RESULTS
  Increasing the Metolose® concentrations (0.5-4%, w/w), T (t) can be decreased, but it also altered the consistency of gel. pH does not affect the T (t). The water-soluble salts allowed reducing the gelation temperature to 37°C. Sodium monohydrogen phosphate in 4.5% concentration was found to be the most appropriate. The impact of examined factors on in vitro drug release of piroxicam from the in situ-formed gel was characterized according to Fickian diffusion. Metolose® and the chosen salt did not cause any morphological damage on the rectal tissues.
  
  
  CONCLUSIONS
  According to our study, Metolose® has the physical and chemical potential to be used as base for liquid suppositories.
authors.affiliation: Department of Pharmaceutics, Semmelweis University, Budapest, Hungary. pasztor.eszter@citromail.hu
authors.forename: E
authors.initials: E
authors.lastname: Pásztor
authors.forename: A
authors.initials: A
authors.lastname: Makó
authors.forename: G
authors.initials: G
authors.lastname: Csóka
authors.forename: Zs
authors.initials: Z
authors.lastname: Fenyvesi
authors.forename: R
authors.initials: R
authors.lastname: Benko
authors.forename: M
authors.initials: M
authors.lastname: Prosszer
authors.forename: S
authors.initials: S
authors.lastname: Marton
authors.forename: I
authors.initials: I
authors.lastname: Antal
authors.forename: I
authors.initials: I
authors.lastname: Klebovich
mesh_terms: D000285:Administration, Rectal; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D005782:Gels / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008297:Male; D008747:Methylcellulose / Q000737:chemistry*; D008954:Models, Biological; D010710:Phosphates / Q000737:chemistry*; D010894:Piroxicam / Q000008:administration & dosage / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013488:Suppositories / Q000737:chemistry*; D013696:Temperature
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005782:Gels; D010710:Phosphates; D013488:Suppositories; D010894:Piroxicam; D008747:Methylcellulose; C018279:sodium phosphate