Formulation of Extended Release Theophylline Tablets Experimental, Modelling and Bioequivalence Studies

Abstract

Extended release drugs formulations are intended to continuously release medication over a prolonged period, after a single dose. Drugs which have a narrow therapeutic window and a moderate half life are good candidates for such formulations. One approach to such formulations is to embed the drug in a matrix which 'would act as a release retardant. We describe here our studies on the formulations of an extended release theophylline tablet using polymer matrices. Different acrylate copolymers sold in the market under the "Eudragit" label were subjected to experiment. Microcrystalline cellulose and calcium sulphate dihydrate were used as filler excepients. The theophylline release patterns of the different formulations were studied, at 37aC in phosplate buffers. The theophylline concentration were measured by Ul/ absorption spectroscopy A careful study of the release patterns of different formulations let to a formulation using Eudragit=E RSPO, a trimenthylammonioethyl methacrylate copolymer and calcium sulphate dihydrate, which conformed with the following release pattern in accordance with USP 25.

Time (hours) % Drug Released

1 10 - 30 2 30 - 55 4 55 - 80 8 >80

This formulations 'was used to prepare tablets with two dosages, paediatric dose (125 mg) and adult dose (250 mg). The adult dose was subjected to a bioequivalence study against an established commercially available slow release 250 mg formulation (Neulin 250 SR, 3M Pharmaceuticals, Australia) Twenty healthy male volunteers participated in the study. Theophylline concentrations in serum were determined by Fluorescence Polarization Immunoassay. There was no significant difference between the two formulations in basic bio availability and pharmacokinetic parameters (AUC CiliaIa'nd Tlllal The new Theophylline ER 125 mgformulation developed is nOH'being manufactured by the State Pharmaceutical Manufacturing Corporation (SPMC). a. State Pharmaceutical Manufacturing Corporation, Sri Johne Kothalawala Estate, Ratmalana, Sri Lanka 071-1815117 b. Dean Faculty 0.( Natural Science, University of Sri Jayawrdanapura, Nugegoda c. Pharmacology Division, Faculty of Medicine, University of Sri Jayawrdanapura, Nugegoda.