title: Development of Metronidazole-Loaded Colon-Targeted Microparticulate Drug Delivery System.
abstract: BACKGROUND
  Crohn’s disease and ulcerative colitis are the main autoimmune inflammatory bowel diseases. Metronidazole is the most commonly used drug for the treatment of Crohn’s disease. However, the pharmacokinetic profile of this drug indicates that the largest amount of the drug is absorbed from the upper part of the intestines and very little concentration of the drugs reaches the colon.Objectives: The aim of this investigation was to formulate metronidazole loaded microspheres for the efficient therapy of inflammatory bowel diseases.Material and Methods: Microspheres were prepared using the emulsification-solvent evaporation method. The effect of Eudragit S100 concentration and the ratio of liquid paraffin (light: heavy) on percentage yield, particle size, morphology, drug encapsulation and in vitro drug release was examined. Drug-polymer interaction was investigated using Fourier Transformed Infrared Spectroscopy (FTIR).
  
  
  RESULTS
  The results showed that the particle had good flow properties, encapsulation efficiency (56.11 ・} 1.51–81.02 ・} 2.14%)and cumulative drug release (64.14 ・} 0.83–79.69 ・} 2.45%) in a phosphate buffer (pH 6.8) after 10 h of the dissolution study.An increased particle size was observed with an increasing polymer concentration. It was observed that the Eudragit had a positive effect on the drug encapsulation and negative effect on drug release. Aggregation of drug-polymer droplets was observed at a lower level of magnesium stearate during microsphere preparation. The results of FTIR spectroscopy revealed the absence of any drug-polymer interactions. However, slight peak shifting and suppression in peak height was observed.This might be due to the minor ionic interactions. The microspheres were discrete, spherical and free-flowing. The spherical shape of the microspheres was confirmed from SEM photomicrographs. The developed microspheres showed a controlled drug release and were found to follow Higuchi’s model. The release mechanism of metronidazole from the microspheres was Fickian diffusion without swelling.
  
  
  CONCLUSIONS
  The results suggest that the developed microspheres could enhance drug entrapment, and inflect the drug release.
authors.affiliation: Department of Pharmaceutics, Laureate Institute of Pharmacy, Kathog, Tehsil-Dehra, Distt-Kangra, Himachal Pradesh, India.
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Department of Pharmaceutics, Laureate Institute of Pharmacy, Kathog, Tehsil-Dehra, Distt-Kangra, Himachal Pradesh, India.
authors.forename: Rajendra
authors.initials: R
authors.lastname: Awasthi
mesh_terms: D003106:Colon; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D006801:Humans; D008795:Metronidazole / Q000008:administration & dosage* / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D008899:Mineral Oil; D010316:Particle Size; D011109:Polymethacrylic Acids / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D004337:Drug Carriers; D011109:Polymethacrylic Acids; D008795:Metronidazole; C038300:methylmethacrylate-methacrylic acid copolymer; D008899:Mineral Oil