title: Lipids bearing extruded-spheronized pellets for extended release of poorly soluble antiemetic agent-Meclizine HCl.
abstract: BACKGROUND
  Antiemetic agent Meclizine HCl, widely prescribed in vertigo, is available only in immediate release dosage forms. The approved therapeutic dose and shorter elimination half-life make Meclizine HCl a potential candidate to be formulated in extended release dosage form. This study was aimed to develop extended release Meclizine HCl pellets by extrusion spheronization using natural and synthetic lipids. Influence of lipid type, drug/lipid ratio and combinations of different lipids on drug release and sphericity of pellets were evaluated.
  
  
  METHODS
  Thirty two formulations were prepared with four different lipids, Glyceryl monostearate (Geleol®), Glyceryl palmitostearate (Precirol®), Glyceryl behenate (Compritol®) and Carnauba wax, utilized either alone or in combinations of drug/lipid ratio of 1:0.5-1:3. Dissolution studies were performed at variable pH and release kinetics were analyzed. Fourier transform infrared spectroscopy was conducted and no drug lipid interaction was found.
  
  
  RESULTS
  Sphericity indicated by shape factor (eR) varied with type and concentration of lipids: Geleol®(eR= 0.891-0.997), Precirol®(eR= 0.611-0.743), Compritol®(eR= 0.665-0.729) and Carnauba wax (eR= 0.499-0.551). Highly spherical pellets were obtained with Geleol®(Aspect ratio = 1.005-1.052) whereas irregularly shaped pellets were formed using Carnauba wax (Aspect ratio = 1.153-1.309). Drug release was effectively controlled by three different combinations of lipids: (i) Geleol®and Compritol®, (ii) Geleol®and Carnauba wax and (iii) Geleol®, Compritol®and Carnauba wax. Scanning electron microscopy of Compritol®pellets showed smooth surface with pores, whereas, irregular rough surface with hollow depressions was observed in Carnauba wax pellets. Energy dispersive spectroscopy indicated elemental composition of lipid matrix pellets. Kinetics of (i) Geleol®and Compritol®pellets, explained by Korsmeyer-Peppas (R2= 0.978-0.993) indicated non-Fickian diffusion (n = 0.519-0.597). Combinations of (ii) Geleol®and Carnauba wax and (iii) Geleol®, Compritol®and Carnauba wax pellets followed Zero-order (R2= 0.991-0.995). Similarity test was performed using combination of Geleol®and Compritol®(i) as a reference.
  
  
  CONCLUSIONS
  Matrices for the extended release of Meclizine HCl from extruded-spheronized pellets were successfully formed by using three lipids (Geleol®, Compritol®and Carnauba wax) in different combinations. The encapsulated pellets of Meclizine HCl can be effectively used for treatment of motion sickness, nausea and vertigo for extended period of time.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy & Pharmaceutical Sciences, University of Karachi, Karachi, 75270, Pakistan.
authors.forename: Faaiza
authors.initials: F
authors.lastname: Qazi
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy & Pharmaceutical Sciences, University of Karachi, Karachi, 75270, Pakistan. harrisshoaib2000@yahoo.com.
authors.forename: Muhammad Harris
authors.initials: MH
authors.lastname: Shoaib
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy & Pharmaceutical Sciences, University of Karachi, Karachi, 75270, Pakistan.
authors.forename: Rabia Ismail
authors.initials: RI
authors.lastname: Yousuf
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy & Pharmaceutical Sciences, University of Karachi, Karachi, 75270, Pakistan.
authors.forename: Muhammad Iqbal
authors.initials: MI
authors.lastname: Nasiri
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy & Pharmaceutical Sciences, University of Karachi, Karachi, 75270, Pakistan.
authors.forename: Kamran
authors.initials: K
authors.lastname: Ahmed
authors.affiliation: Research Institute of Pharmaceutical Sciences, Department of Pharmacognosy, Faculty of Pharmacy & Pharmaceutical Sciences, University of Karachi, Karachi, 75270, Pakistan.
authors.forename: Mansoor
authors.initials: M
authors.lastname: Ahmad
mesh_terms: D000284:Administration, Oral; D000932:Antiemetics / Q000008:administration & dosage* / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D004075:Diglycerides / Q000737:chemistry; D004339:Drug Compounding; D065546:Drug Liberation; D004355:Drug Stability; D004356:Drug Storage; D005227:Fatty Acids / Q000737:chemistry*; D005989:Glycerides / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000737:chemistry*; D008468:Meclizine / Q000008:administration & dosage* / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D014677:Pharmaceutical Vehicles / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D014867:Water / Q000032:analysis; D014885:Waxes / Q000737:chemistry*
chemical_list: D000932:Antiemetics; D003692:Delayed-Action Preparations; D004075:Diglycerides; D005227:Fatty Acids; D005989:Glycerides; D008055:Lipids; D014677:Pharmaceutical Vehicles; D014885:Waxes; D014867:Water; C086409:glyceryl behenate; C048159:glyceryl monostearate; D008468:Meclizine; C009032:precirol; C026344:carnauba wax
keywords: Extended release; Extrusion spheronization; Lipids; Meclizine HCl; Pellets