title: Once daily controlled release matrix tablet of Prochlorperazine maleate: influence of Ethocel® and/or Methocel® on in vitro drug release and bioavailability.
abstract: BACKGROUND
  Controlled release (CR) matrix tablet of Prochlorperazine maleate was developed to improve its patient compliance.
  
  
  METHODS
  Tablet formulations F1, F2 and F3 based on different concentrations of Methocel(®) K100 LV-CR Premium, were compacted by direct compression method while tablet formulations F4, F5 and F6, based on distinct blends of Methocel(®) K100 LV-CR Premium and Ethocel(®) Standard 7FP Premium, were compressed by flow-bound dry granulation-slugging method. The prepared powder mixtures, granules and tablets were evaluated for their physicochemical performance. Bioequivalence study of the optimized test tablet versus reference-conventional Stemitil(®) tablet was conducted on rabbits, using HPLC-UV system at λ(max) 254 nm.
  
  
  RESULTS
  The test tablet, containing 28% Methocel(®) and 58% Ethocel(®) (F6) exhibited desired zero order kinetics for 24 h and was found stable at accelerated storage conditions for 6 months. In vitro drug release rate decreased as the Ethocel(®) content in the blend was increased, perhaps due to slower penetrability of water. Hydrodynamic conditions and hardness of tablets could not affect drug release kinetics. The tablet displayed significantly (p < 0.05) optimized peak drug concentration-C(max) (45 ± 3.42 vs. 64.5 ± 4.03), extended half life-t(1/2) (16.071 ± 3.97 vs. 5.257 ± 1.314 h) and bioequivalence to the reference tablet taken three times a day (1409 ± 15 ng·h/mL vs. 1346 ± 23 ng h/mL). The tablet showed strong Level A correlation (R(2) = 0.8458) between drug absorbed in vivo and drug released in vitro.
  
  
  CONCLUSIONS
  The developed tablet may be adopted by pharmaceutical industry to improve patient compliance of the Prochlorperazine maleate.
authors.affiliation: Pharmacy, Univeristy of Peshawar, Peshawar 25120 Pakistan. amir_badshah@upesh.edu.pk
authors.forename: Amir
authors.initials: A
authors.lastname: Badshah
authors.forename: Fazal
authors.initials: F
authors.lastname: Subhan
authors.forename: Nisar Hussain
authors.initials: NH
authors.lastname: Shah
authors.forename: Nadeem Irfan
authors.initials: NI
authors.lastname: Bukhari
authors.forename: Muhammad
authors.initials: M
authors.lastname: Saeed
authors.forename: Kifayat Ullah
authors.initials: KU
authors.lastname: Shah
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D002482:Cellulose / Q000031:analogs & derivatives* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D006801:Humans; D008297:Male; D008747:Methylcellulose / Q000494:pharmacology*; D011108:Polymers / Q000737:chemistry / Q000493:pharmacokinetics; D011346:Prochlorperazine / Q000737:chemistry / Q000493:pharmacokinetics*; D011817:Rabbits; D013607:Tablets; D013810:Therapeutic Equivalency
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D011108:Polymers; D013607:Tablets; C013517:ethyl cellulose; D002482:Cellulose; D008747:Methylcellulose; D011346:Prochlorperazine