title: Formulation optimization of gastroretentive drug delivery system for allopurinol using experimental design.
abstract: OBJECTIVE
  The objective of the study was to develop gastroretentive dosage form (GRDF) for allopurinol (ALP) using combined approaches of mucoadhesion and floating systems. GRDF was systematically optimized using 3(2)-full factorial design.
  
  
  METHODS
  Concentrations of sodium carboxymethyl cellulose (X1) and concentration of polyoxyethylene oxide WSR 303 (X2) were selected as independent variables, whereas gastroretentive parameters like total floating time (TFT) (Y1), mucoadhesive force (MF) (Y2), time required for 10% drug release (Y3) and time required for 80% drug release (Y4) were selected as dependent variables in development of robust GRDF of ALP. GRDF was evaluated for gastroretentive parameters such as floating lag time (FLT) and TFT, MF using texture analyzer and ex vivo residence time using modified disintegration test apparatus. Roentgenography study of optimized formulation was conducted to evaluate in vivo gastro retentive behavior using albino rabbits.
  
  
  RESULTS
  Developed tablets showed immediate in situ gas generation and exhibited FLT of 1.68 s after placing into simulated gastric fluid, which lead to buoyancy as well as controlled drug release for 24 h with zero-order drug release kinetics. The optimized formulation was selected based on in vitro drug release characteristics. In vivo retention of optimized formulation was corroborated using roentgenography studies.
  
  
  CONCLUSIONS
  The study concluded that the combination of mucoadhesive and floating approaches for GRDF aids to achieve desired gastroretentive performance and drug release properties for ALP. The formulation scientists may adopt these formulation strategies for drugs suitable for the development of GRDF.
authors.affiliation: Nirma University, Institute of Pharmacy, Department of Pharmaceutics and Pharmaceutical Technology , S. G. Highway, Ahmedabad-382 481, Ahmedabad, Gujarat , India.
authors.forename: Om Prakash
authors.initials: OP
authors.lastname: Sharma
authors.forename: Mahek V
authors.initials: MV
authors.lastname: Shah
authors.forename: Dhaivat C
authors.initials: DC
authors.lastname: Parikh
authors.forename: Tejal A
authors.initials: TA
authors.lastname: Mehta
mesh_terms: D000493:Allopurinol / Q000008:administration & dosage*; D000818:Animals; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D005260:Female; D008297:Male; D011817:Rabbits; D013270:Stomach; D013607:Tablets
chemical_list: D003692:Delayed-Action Preparations; D013607:Tablets; D000493:Allopurinol; D002266:Carboxymethylcellulose Sodium
keywords: floating; full factorial design; gastro-retentive; mucoadhesive; texture analysis