Modeling of drug release from multi-unit dosage tablets of theophylline

  • MU Uhumwangho
  • RS Okor
Keywords: Theophylline, modeling, drug release, multi-unit dose tablets.


A model of multi-unit dose tablets of theophylline (dose, 600 mg) has been designed to give a prompt release dose (200 mg) in the first 1 h and the remaining sustained release dose (400 mg) to be released
over 11 h at a first order release rate constant of 0.24 h-1. The prompt release component (A) consisted of conventional granules of the drug while the sustained release component (B) was made up of matrix
granules of the drug obtained by melt granulation i.e. granulating the drug powder with a melted wax (carnuba). To form the multi-unit dose tablets, granules of A and B were mixed together in various
proportions in the ratios (A: B) 2:1, 1:1 and 1:2. The disintegration times of the tablets and their dissolution profiles were measured to investigate consistence with the model. The results showed that
the tablets generally disintegrated readily within 10 min irrespective of the proportion of A to B. Of the various formulations tested, only the formulation consisting of A and B in the ratio 1:1 gave dissolution
profile that was comparable to that of the model. The following were the dissolution parameters of this formulation: the maximum release (m) = 580 mg, prompt release dose (mp) = 180 mg, time to attain
maximum release (t) = 11 h and first order release rate constant (k1) = 0.27 h-1 which is comparable with the release data for the model. The other formulations deviated by giving mp and t that were either too
high or too low compared with those of the model. The indication is that the prompt release dose was not determined only by the amount of A in the multi-unit dose formulation but also by the amount of B,
attributable to the deformation of granules of A into B during tableting.

Journal Identifiers

eISSN: 1684-5315