Influence of dissolution media pH and USP1 basket speed on erosion and disintegration characteristics of immediate release metformin hydrochloride tablets

• Published in: Pharmaceutical development and technology Vol. 20; no. 5; p. 540
• Main Authors: Desai, Divyakant, Wong, Benjamin, Huang, Yande, Tang, Dan, Hemenway, Jeffrey, Paruchuri, Srinivasa, Guo, Hang, Hsieh, Daniel, Timmins, Peter
• Format: Journal Article
• Language: English
• Published: England 04.07.2015
• Subjects: Carboxymethylcellulose Sodium - chemistry; Diffusion; Drug Liberation; Hydrogen-Ion Concentration; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - chemistry; Metformin - administration & dosage; Metformin - chemistry; Pharmaceutic Aids - chemistry; Povidone - chemistry; Solubility; Tablets; erosion; super-disintegrant; Diffusion; disintegration; diffusion boundary layer
• ISSN: 1097-9867
• DOI: 10.3109/10837450.2014.892132

To investigate the influence of the pH of the dissolution medium on immediate release 850 mg metformin hydrochloride tablets. 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. 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. 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.