title: Fusion Method for Solubility and Dissolution Rate Enhancement of Ibuprofen Using Block Copolymer Poloxamer 407.
abstract: Aim of current research was to prepare ibuprofen-poloxamer 407 binary mixtures using fusion method and characterize them for their physicochemical and performance properties. Binary mixtures of ibuprofen and poloxamer were prepared in three different ratios (1:0.25, 1:0.5, and 1:0.75, respectively) using a water-jacketed high shear mixer. In vitro dissolution and saturation solubility studies were carried out for the drug, physical mixtures, and formulations for all ratios in de-ionized water, 0.1 N HCl (pH = 1.2), and phosphate buffer (pH = 7.2). Thermal and physical characterization of samples was done using modulated differential scanning calorimetry (mDSC), X-ray powder diffraction (XRD), and infrared spectroscopy (FTIR). Flow properties were evaluated using a powder rheometer. Maximum solubility enhancement was seen in acidic media for fused formulations where the ratio 1:0.75 had 18-fold increase. In vitro dissolution studies showed dissolution rate enhancement for physical mixtures and the formulations in all three media. The most pronounced effect was seen for formulation (1:0.75) in acidic media where the cumulative drug release was 58.27% while for drug, it was 3.67%. Model independent statistical methods and ANOVA based methods were used to check the significance of difference in the dissolution profiles. Thermograms from mDSC showed a characteristic peak for all formulations with Tpeakof around 45°C which suggested formation of a eutectic mixture. XRD data displayed that crystalline nature of ibuprofen was intact in the formulations. This work shows the effect of eutectic formation and micellar solubilization between ibuprofen and poloxamer at the given ratios on its solubility and dissolution rate enhancement.
authors.affiliation: Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Division of Pharmaceutical Sciences, Long Island University, Brooklyn, New York, 11201, USA.
authors.forename: Rohit P
authors.initials: RP
authors.lastname: Dugar
authors.affiliation: Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Division of Pharmaceutical Sciences, Long Island University, Brooklyn, New York, 11201, USA.
authors.forename: Bhavin Y
authors.initials: BY
authors.lastname: Gajera
authors.affiliation: Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Division of Pharmaceutical Sciences, Long Island University, Brooklyn, New York, 11201, USA. rutesh.dave@liu.edu.
authors.forename: Rutesh H
authors.initials: RH
authors.lastname: Dave
mesh_terms: D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004339:Drug Compounding / Q000379:methods*; D005079:Excipients / Q000737:chemistry; D007052:Ibuprofen / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning / Q000379:methods; D020442:Poloxamer / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011208:Powders / Q000737:chemistry; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D005079:Excipients; D011108:Polymers; D011208:Powders; D014867:Water; D020442:Poloxamer; D007052:Ibuprofen
keywords: dissolution rate enhancement; fusion method; ibuprofen; poloxamer; solubility enhancement