title: Improved stability of solid dispersions of manidipine with polyethylene glycol 4000/copovidone blends: application of ternary phase diagram.
abstract: BACKGROUND
  Manidipine (MDP) is generally used clinically as an antihypertensive agent; however, the bioavailability of orally administered MDP is limited due to their very low water solubility.
  
  
  OBJECTIVE
  The objectives of this research were, therefore, to increase the solubility of MDP by the formation of ternary solid dispersions (tSD) with polyethylene glycol 4000 (PEG4000) and copovidone and to improve their stability.
  
  
  METHODS
  Solid ternary phase diagram was constructed to find homogeneous solid dispersion region after melting and solidifying at low temperature with different quenching substances. The pulverized powder of solid dispersions was then determined, for their physicochemical properties, by differential scanning calorimetry, powder X-ray diffractometry, Fourier transform infrared (FTIR) spectroscopy and hot stage microscopy. The solubility and dissolution of MDP from the tSD were investigated. The physical stability of tSD was also determined under accelerated condition at 40 °C/75% relative humidity (RH) for 6 months.
  
  
  CONCLUSIONS
  The results showed that MDP was molecularly dispersed in PEG4000 and copovidone when the tSD was created from homogeneous region of solid ternary phase diagram. FTIR results confirmed that strong hydrogen bonding was presented between MDP and copovidone, leading to a significant increase in the solubility and dissolution of MDP. After storage at accelerated condition (40 °C/75%RH) for 6 months, the tSD still showed a good appearance and high solubility.
  
  
  CONCLUSIONS
  The results of this study suggest that tSD prepared by melting has promising potential for oral administration and may be an efficacious approach for improving the therapeutic potential of MDP.
authors.affiliation: a Department of Pharmaceutical Technology, Faculty of Pharmacy , Silpakorn University , Nakhon Pathom , Thailand.|b Pharmaceutical Biopolymer Group (PBiG), Faculty of Pharmacy , Silpakorn University , Nakhon Pathom , Thailand.
authors.forename: Benchawan
authors.initials: B
authors.lastname: Chamsai
authors.affiliation: a Department of Pharmaceutical Technology, Faculty of Pharmacy , Silpakorn University , Nakhon Pathom , Thailand.|b Pharmaceutical Biopolymer Group (PBiG), Faculty of Pharmacy , Silpakorn University , Nakhon Pathom , Thailand.
authors.forename: Sontaya
authors.initials: S
authors.lastname: Limmatvapirat
authors.affiliation: c Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences , Naresuan University , Phitsanulok , Thailand.
authors.forename: Srisagul
authors.initials: S
authors.lastname: Sungthongjeen
authors.affiliation: a Department of Pharmaceutical Technology, Faculty of Pharmacy , Silpakorn University , Nakhon Pathom , Thailand.|b Pharmaceutical Biopolymer Group (PBiG), Faculty of Pharmacy , Silpakorn University , Nakhon Pathom , Thailand.
authors.forename: Pornsak
authors.initials: P
authors.lastname: Sriamornsak
mesh_terms: D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004095:Dihydropyridines / Q000138:chemical synthesis*; D004355:Drug Stability; D009578:Nitrobenzenes; D010879:Piperazines; D011092:Polyethylene Glycols / Q000138:chemical synthesis*; D011759:Pyrrolidines / Q000138:chemical synthesis*; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D014753:Vinyl Compounds / Q000138:chemical synthesis*
chemical_list: D004095:Dihydropyridines; D009578:Nitrobenzenes; D010879:Piperazines; D011759:Pyrrolidines; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); D011092:Polyethylene Glycols; C000595214:polyethylene glycol 4000; C054218:manidipine
keywords: Manidipine; poorly water-soluble drug; ternary phase diagram; ternary solid dispersion