Bioadhesive dosage form for peroral administration of timolol base.

Timolol base was prepared from its maleate salt and checked for purity, pKa (9.03) and n-octanol/phosphate buffer pH 6.6 partition coefficient (1.72). The rate of swelling of sodium carboxymethylcellulose, Carbopol 934 (CP) and hydroxypropylcellulose (HPC) was examined prior to use in bioadhesive compacts with the model drug methylene blue to study their influence on device integrity and drug diffusion. A final compact containing a core of timolol base and Precirol, a bioadhesive layer of CP and HPC, and a cap of magnesium stearate gave sustained release of the drug in simulated saliva pH 6.6. After preliminary evaluation in dogs, the compact was evaluated in a panel of humans in whom it was shown that the flux of drug could be increased from 70 to 127 micrograms mm-2 h-1 by inclusion of the penetration enhancer sodium lauryl-sulphate into the core formulation.