Formulation study and drug release mechanism of a new theophylline sustained-release preparation.
Two matrix theophylline tablets with different release mechanisms were compared. Tablet A was a swelling/disintegration-type wax matrix made of hydrophobic wax granules, consisting of stearic acid, hydrogenated oil and glycerol esters of fatty acids, and hydrophilic polymer granules composed primarily of hydroxypropyl methylcellulose (HPMC). We named Tablet A the cluster tablet. Tablet B was a gel matrix made of hydrophobic ethylcellulose granules, consisting of ethylcellulose and hydrogenated oil, and hydrophilic polymer granules consisting of HPMC and hydroxylpropylmethylcellulose acetate succinate (HPMCAS). The formulations were screened in vitro according to their dissolution characteristics. The drug release from each preparation was analyzed using release kinetics theories. In Tablet A, the value of the exponent(n) representing the apparent diffusion mechanism determined from the Korsmeyer-Peppas model equation was about 0.6 and was unlikely to be affected by the rotation speed. In Tablet B, the value of the exponent(n) by the Korsmeyer-Peppas model equation changed with the paddle rotation speed. These results suggested that the drug release mechanism of Tablet B is greatly affected by the extent of physical force in the gastrointestinal tract.
Hayashi
Tetsuo
T
Central Research Laboratories, SSP Co., Ltd., Nanpeidai 1143, Narita-shi, Chiba, and School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan. Tetsuo.Hayashi@ssp.co.jp
Kanbe
Hideyoshi
H
Okada
Minoru
M
Suzuki
Makoto
M
Ikeda
Yasuo
Y
Onuki
Yoichi
Y
Kaneko
Tetsuo
T
Sonobe
Takashi
T
D003692:Delayed-Action Preparations; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry*; D007700:Kinetics; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D013607:Tablets; D013806:Theophylline / Q000737:chemistry*
D003692:Delayed-Action Preparations; D005079:Excipients; D011108:Polymers; D013607:Tablets; D013806:Theophylline