Development of a novel combination tablet containing trimebutine maleate and mosapride citrate for the treatment of functional dyspepsia.
To develop a novel combination tablet which contained 100 mg trimebutine maleate and 5 mg mosapride citrate (TMCT) for the treatment of functional dyspepsia, the wet granulation method was used to prepare TMCTs with various amounts of diluents and stabilizers. The levels of impurities, the stability and the dissolution of the TMCTs were investigated. The oral bioavailability of drugs in the TMCTs was then evaluated and compared to the simultaneous oral administration of trimebutine maleate-loaded and mosapride citrate-loaded commercial products in the beagle dog. Among the diluents tested, D-mannitol was selected, since the microcrystalline cellulose and lactose did not inhibit the production of drug impurities due to their hygroscopic properties and chemical interactions, respectively. Furthermore, succinic acid was selected as the stabilizer because it gave the lowest level of total drug impurities of the organic acids tested. The combination tablet of trimebutine maleate and mosapride citrate prepared with D-mannitol and succinic acid gave a total drug content higher than 95% and total impurities lower than 0.5% at 25°C/60% RH and 40°C/75% RH during a 6-month period, indicating that the tablets were stable for at least 6 months. Furthermore, this combination tablet showed a similar dissolution to the trimebutine maleate-loaded and mosapride citrate-loaded commercial products and gave insignificantly different absorption compared to these commercial products in beagle dogs. Thus, the combination tablet of trimebutine maleate and mosapride citrate prepared with D-mannitol and succinic acid would be a stable and effective oral pharmaceutical product for the treatment of functional dyspepsia.
Cho
Kwan Hyung
KH
College of Pharmacy, Yeungnam University, 214-1 Dae-Dong, Gyongsan 712-749, South Korea.
Choi
Young Keun
YK
Kang
Jun Heok
JH
Choi
Han-Gon
HG
Yong
Chul Soon
CS
Park
Young-Joon
YJ
D000818:Animals; D001549:Benzamides / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001682:Biological Availability; D004285:Dogs; D004338:Drug Combinations; D004339:Drug Compounding; D004355:Drug Stability; D004415:Dyspepsia / Q000188:drug therapy*; D005079:Excipients / Q000737:chemistry; D005765:Gastrointestinal Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008353:Mannitol / Q000737:chemistry; D009025:Morpholines / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012995:Solubility; D019802:Succinic Acid / Q000737:chemistry; D013607:Tablets; D014287:Trimebutine / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use
D001549:Benzamides; D004338:Drug Combinations; D005079:Excipients; D005765:Gastrointestinal Agents; D009025:Morpholines; D013607:Tablets; D008353:Mannitol; D019802:Succinic Acid; C062720:mosapride; D014287:Trimebutine