Improved stability of Opalmon tablets under humid conditions IV: effect of polysaccharides and disintegrants on the stability and dissolution property of Opalmon tablets.
We studied the effects of dextran, dextrin, and disintegrants on the chemical stability of Opalmon tablets containing Limaprost-alfadex (Limaprost/alpha-cyclodextrin complex) and found that the addition of dextran or dextrin significantly improved the chemical stability of Opalmon tablets under high humidity, compared to lactose. We also examined how dextran stabilizes Limaprost in Opalmon tablets and studied the formulation of Opalmon tablets in order to achieve higher chemical stability, rapid dissolution and reduced stickiness. The results suggested that dextran increases stabilization after moisture adsorption by decreasing the dissociation of Limaprost-alfadex to the free drug and alpha-cyclodextrin in the dextran matrix, when compared with the lactose matrix. The stickiness of Opalmon tablets containing dextran and dextrin was negligible when dextran and dextrin amounted to less than 20% of the formulation. By selecting a proper disintegrant, we obtained Opalmon tablets with higher chemical stability and rapid dissolution properties.
Sekiya
Noboru
N
Pharmaceutical Development Laboratories, Ono Pharmaceutical Co., Ltd.,Osaka, Japan. sekiya@ono.co.jp
Nishiwaki
Atsushi
A
Nishiura
Akio
A
Yamamoto
Masanobu
M
Takeda
Kazuhisa
K
Iohara
Daisuke
D
Hirayama
Fumitoshi
F
Arima
Hidetoshi
H
Uekama
Kaneto
K
D000527:Alprostadil / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D003911:Dextrans / Q000737:chemistry / Q000493:pharmacokinetics; D003912:Dextrins / Q000737:chemistry / Q000493:pharmacokinetics; D019483:Disintegrins / Q000737:chemistry / Q000493:pharmacokinetics*; D005079:Excipients; D006813:Humidity; D015394:Molecular Structure; D011134:Polysaccharides / Q000493:pharmacokinetics*; D012995:Solubility; D013607:Tablets; D047391:alpha-Cyclodextrins / Q000737:chemistry / Q000493:pharmacokinetics*
D003911:Dextrans; D003912:Dextrins; D019483:Disintegrins; D005079:Excipients; D011134:Polysaccharides; D013607:Tablets; D047391:alpha-Cyclodextrins; C525749:limaprost-alfadex; D000527:Alprostadil; C059238:limaprost