Dissolution of theophylline from film-coated slow release mini-tablets in various dissolution media.
The dissolution of an experimental formulation of film-coated slow release theophylline mini-tablets has been investigated using the USP paddle apparatus in test media at pH 1.2 (hydrochloric acid), pH 5.4 and 7.4 (phosphate buffers) at 37 degrees C. Monitoring of in-vitro theophylline release over 12 h, under identical hydrodynamic conditions, showed that the dissolution rate at pH 1.2 is substantially greater (95% of total drug content released in less than 10 h) than that in phosphate buffers. The maximum release after 12 h was approximately 20 and 30% of total drug content of the tablet at pH 5.4 and 7.4, respectively. However, in vivo bioavailability after oral administration of tablets to rabbits corresponded to over 95% of total drug, compared with the same dose administered intravenously. The retarded drug release during in-vitro dissolution in phosphate buffer was attributed to a possible interaction of phosphate ions with theophylline molecules at the tablet core-coat interface. These findings indicate that both rate and extent of theophylline release from the slow release coated mini-tablets are highly sensitive to phosphate buffers. The data also emphasize the usefulness of an animal model for assessment of in-vivo drug release and subsequent absorption, during the development of modified release dosage forms.
Fassihi
A R
AR
Department of Pharmacy, University of the Witwatersrand, Medical School, Johannesburg, South Africa.
Munday
D L
DL
D000818:Animals; D001682:Biological Availability; D002266:Carboxymethylcellulose Sodium; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D011817:Rabbits; D012995:Solubility; D012997:Solvents; D013607:Tablets; D013806:Theophylline / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics
D003692:Delayed-Action Preparations; D012997:Solvents; D013607:Tablets; D013806:Theophylline; D002266:Carboxymethylcellulose Sodium