title: In-vitro characterization of 5-aminosalicylic acid release from MMX mesalamine tablets and determination of tablet coating thickness.
abstract: BACKGROUND
  Substantial variability in gastrointestinal pH is observed in patients with ulcerative colitis (UC). We characterized the effect of pH on 5-aminosalicylic acid (5-ASA) release from MMX mesalamine tablets (Shire Pharmaceuticals Inc., Wayne, PA, USA), examined thickness/uniformity of tablet film coatings, and explored the influence of simulating altered gastrointestinal motility.
  
  
  METHODS
  Nondestructive, three-dimensional, terahertz pulse imaging (TPI) was used to characterize the film coating of three lots of MMX mesalamine tablets (n=36). Thereafter, 5-ASA release from these tablets was evaluated using United States Pharmacopeia (USP) apparatus II at pH 6.8 and 7.2. Onset of tablet film-coat breach and mean dissolution time were determined for each lot. 5-ASA release was also assessed at three different paddle rotation speeds (50, 75, and 100 rpm) at pH 7.2.
  
  
  RESULTS
  The mean ± SD film-coating thickness of the three lots of MMX mesalamine tablets were 109.2 ± 16.8, 113.1 ± 19.5, and 113.8 ± 19.8 μM, respectively. At pH 6.8 (100 rpm), the onset of film-coat breach was 10-30 minutes, whereas at pH 7.2 this was observed within 10 minutes. 5-ASA release was uniform at both pH conditions, with minimal lot-to-lot variability. Complete drug release was achieved within 6 hours under both pH conditions. 5-ASA release increased in proportion with paddle speed, but remained prolonged at all speeds.
  
  
  CONCLUSIONS
  5-ASA release from MMX mesalamine is unaffected by normal variations in simulated intracolonic pH. The dissolution profile of 5-ASA from MMX mesalamine tablets may be attributed to consistent outer film coatings and the hydrogel-forming matrix that controls the drug release after dissolution of the film coating.
authors.affiliation: Shire Pharmaceuticals Inc., 725 Chesterbrook Blvd, Wayne, PA, Pennsylvania 19087, USA. stenjarla@shire.com
authors.forename: Srini
authors.initials: S
authors.lastname: Tenjarla
authors.forename: Adeyinka
authors.initials: A
authors.lastname: Abinusawa
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D005769:Gastrointestinal Motility / Q000187:drug effects; D041981:Gastrointestinal Tract / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D066298:In Vitro Techniques; D019804:Mesalamine / Q000494:pharmacology*; D013608:Tablets, Enteric-Coated / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D013608:Tablets, Enteric-Coated; D019804:Mesalamine