title: Formulation and in vitro, in vivo evaluation of effervescent floating sustained-release imatinib mesylate tablet.
abstract: BACKGROUND
  Imatinib mesylate is an antineoplastic agent which has high absorption in the upper part of the gastrointestinal tract (GIT). Conventional imatinib mesylate (Gleevec) tablets produce rapid and relatively high peak blood levels and requires frequent administration to keep the plasma drug level at an effective range. This might cause side effects, reduced effectiveness and poor therapeutic management. Therefore, floating sustained-release Imatinib tablets were developed to allow the tablets to be released in the upper part of the GIT and overcome the inadequacy of conventional tablets.
  
  
  METHODS
  Floating sustained-release Imatinib mesylate tablets were prepared using the wet granulation method. Tablets were formulated using Hydroxypropyl Methylcellulose (HPMC K4M), with Sodium alginate (SA) and Carbomer 934P (CP) as release-retarding polymers, sodium bicarbonate (NaHCO3) as the effervescent agent and lactose as a filler. Floating behavior, in vitro drug release, and swelling index studies were conducted. Initial and total drug release duration was compared with a commercial tablet (Gleevec) in 0.1 N HCl (pH 1.2) at 37 ± 0.5°C for 24 hours. Tablets were then evaluated for various physical parameters, including weight variation, thickness, hardness, friability, and drug content. Consequently, 6 months of physical stability studies and in vitro gastro-retentive studies were conducted.
  
  
  CONCLUSIONS
  Statistical data analysis revealed that tablets containing a composition of 14.67% w/w HPMC K4M, 10.67%, w/w Na alginate, 1.33%, w/w Carbomer 934P and 9.33%, w/w NaHCO3 produced the most favorable formulation to develop 24-hour sustained-release tablets with optimum floating behavior and satisfactory physicochemical characteristics. Furthermore, in vitro release study revealed that the formulated SR tablet had significantly lower Cmax and higher Tmax compared to the conventional tablet (Gleevec). Thus, formulated SR tablets preserved persistent concentration of plasma up to 24 hours.
  
  
  CONCLUSIONS
  In conclusion, in order to suggest a better drug delivery system with constant favorable release, resulting in optimized absorption and less side effects, formulated CP-HPMC-SA based imatinib mesylate floating sustained-release tablets can be a promising candidate for cancer chemotherapy.
authors.affiliation: Department of Pharmacy, Medical Faculty, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Ali
authors.initials: A
authors.lastname: Kadivar
authors.affiliation: Department of Pharmacy, Medical Faculty, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Behnam
authors.initials: B
authors.lastname: Kamalidehghan
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
authors.forename: Hamid Akbari
authors.initials: HA
authors.lastname: Javar
authors.affiliation: Department of Pharmacy, Medical Faculty, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Ehsan Taghizadeh
authors.initials: ET
authors.lastname: Davoudi
authors.affiliation: Department of Pharmacy, Medical Faculty, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Nurul Dhania
authors.initials: ND
authors.lastname: Zaharuddin
authors.affiliation: Department of Pharmacy, Medical Faculty, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Bahareh
authors.initials: B
authors.lastname: Sabeti
authors.affiliation: Department of Pharmacy, Medical Faculty, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Lip Yong
authors.initials: LY
authors.lastname: Chung
authors.affiliation: Department of Pharmacy, Medical Faculty, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Mohamed Ibrahim
authors.initials: MI
authors.lastname: Noordin
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000464:Alginates / Q000737:chemistry; D000818:Animals; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004355:Drug Stability; D005260:Female; D020723:Glucuronic Acid / Q000737:chemistry; D006244:Hardness; D006603:Hexuronic Acids / Q000737:chemistry; D065347:Hypromellose Derivatives / Q000737:chemistry; D000068877:Imatinib Mesylate / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D007700:Kinetics; D008297:Male; D011817:Rabbits; D017693:Sodium Bicarbonate / Q000737:chemistry; D012995:Solubility; D013607:Tablets / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D000180:Acrylic Resins; D000464:Alginates; D003692:Delayed-Action Preparations; D006603:Hexuronic Acids; D013607:Tablets; D065347:Hypromellose Derivatives; C006903:carbopol 940; D000068877:Imatinib Mesylate; D020723:Glucuronic Acid; D017693:Sodium Bicarbonate