title: Influence of dissolution media pH and USP1 basket speed on erosion and disintegration characteristics of immediate release metformin hydrochloride tablets.
abstract: OBJECTIVE
  To investigate the influence of the pH of the dissolution medium on immediate release 850 mg metformin hydrochloride tablets.
  
  
  METHODS
  A traditional wet granulation method was used to manufacture metformin hydrochloride tablets with or without a disintegrant. Tablet dissolution was conducted using the USP apparatus I at 100 rpm.
  
  
  RESULTS
  In spite of its pH-independent high solubility, metformin hydrochloride tablets dissolved significantly slower in 0.1 N HCl (pH 1.2) and 50 mM pH 4.5 acetate buffer compared with 50 mM pH 6.8 phosphate buffer, the dissolution medium in the USP. Metformin hydrochloride API compressed into a round 1200 mg disk showed a similar trend. When basket rotation speed was increased from 100 to 250 rpm, the dissolution of metformin hydrochloride tablets was similar in all three media. Incorporation of 2% w/w crospovidone in the tablet formulation improved the dissolution although the pH-dependent trend was still evident, but incorporation of 2% w/w croscarmellose sodium resulted in rapid pH-independent tablet dissolution.
  
  
  CONCLUSIONS
  In absence of a disintegrant in the tablet formulation, the dissolution was governed by the erosion-diffusion process. Even for a highly soluble drug, a super-disintegrant was needed in the formulation to overcome the diffusion layer limitation and change the dissolution mechanism from erosion-diffusion to disintegration.
authors.affiliation: Drug Product Science and Technology , New Brunswick, NJ , USA .
authors.forename: Divyakant
authors.initials: D
authors.lastname: Desai
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wong
authors.forename: Yande
authors.initials: Y
authors.lastname: Huang
authors.forename: Dan
authors.initials: D
authors.lastname: Tang
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Hemenway
authors.forename: Srinivasa
authors.initials: S
authors.lastname: Paruchuri
authors.forename: Hang
authors.initials: H
authors.lastname: Guo
authors.forename: Daniel
authors.initials: D
authors.lastname: Hsieh
authors.forename: Peter
authors.initials: P
authors.lastname: Timmins
mesh_terms: D002266:Carboxymethylcellulose Sodium / Q000737:chemistry*; D004058:Diffusion; D065546:Drug Liberation; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry*; D008687:Metformin / Q000008:administration & dosage / Q000737:chemistry*; D010592:Pharmaceutic Aids / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry*; D012995:Solubility; D013607:Tablets
chemical_list: D007004:Hypoglycemic Agents; D010592:Pharmaceutic Aids; D013607:Tablets; D008687:Metformin; D011205:Povidone; D002266:Carboxymethylcellulose Sodium
keywords: Diffusion; diffusion boundary layer; disintegration; erosion; super-disintegrant