Formulation study for lansoprazole fast-disintegrating tablet. II. Effect of triethyl citrate on the quality of the products.
The purpose of this study was to develop enteric-coated microgranules for the lansoprazole fast-disintegrating tablet (LFDT), which is a rapidly disintegrating tablet containing enteric-coated microgranules. In our previous study, it was clarified that sufficient flexibility of the enteric layer was achieved by the optimized combined ratio of methacrylic acid copolymer dispersion to ethyl acrylate-methyl methacrylate copolymer dispersion and adding the optimized concentration of triethyl citrate to reduce the damage during the compression process. However, since triethyl citrate has an unpleasant bitter taste and is especially incompatible with lansoprazole, it adversely affects the taste and stability of lansoprazole in the enteric-coated microgranules. The enteric layer containing macrogol 6000 was proven useful to improve the unpleasant bitter taste and stability of lansoprazole, because macrogol 6000 does not have an unpleasant bitter taste and is more compatible than triethyl citerate. By covering the inner (first enteric layer) and outer side (third enteric layer) of the enteric layer containing triethyl citrate (second enteric layer) with the enteric layer containing macrogol 6000, we resolved the stability problem of lansoprazole and the unpleasant bitter taste. Finally, we developed enteric-coated microgranules comprising seven layers: 1) core, 2) active compound layer, 3) intermediate layer, 4) first enteric layer, 5) second enteric layer, 6) third enteric layer, and 7) over coating layer. The enteric-coated microgranules have the multiple functions of reducing the damage to the enteric layer during the compression process, improving the stability of lansoprazole, and masking the unpleasant bitter taste.
Shimizu
Toshihiro
T
Pharmaceutical Development Laboratories, Pharmaceutical Production Division, Takeda Chemical Industries, Ltd. Ossaka, Japan. Shimizu_Toshihiro@takeda.co.jp
Kameoka
Norio
N
Iki
Hiroshi
H
Tabata
Tetsuro
T
Hamaguchi
Naoru
N
Igari
Yasutaka
Y
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D002021:Buffers; D002626:Chemistry, Pharmaceutical; D002951:Citrates / Q000737:chemistry*; D004344:Drug Incompatibility; D004355:Drug Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D064747:Lansoprazole; D008863:Microspheres; D009853:Omeprazole / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry*; D011092:Polyethylene Glycols; D012463:Saliva / Q000737:chemistry; D013607:Tablets; D013608:Tablets, Enteric-Coated; D013649:Taste
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D002021:Buffers; D002951:Citrates; D007202:Indicators and Reagents; D013607:Tablets; D013608:Tablets, Enteric-Coated; D064747:Lansoprazole; D011092:Polyethylene Glycols; C023001:ethyl citrate; D009853:Omeprazole