Propranolol Hydrochloride Osmotic Capsule with Controlled Onset of Release

Hard gelatin capsule was coated by a cellulose acetate as a semi permeable membrane with or without castor oil and filled with propranolol hydrochloride, and sorbitol as an osmotic agent. After sealing the capsule with white bees wax plug, the onset of release and dissolution rate of the drug were studied. Water penetration into the capsule from the dissolution medium increases simultaneously the osmotic and hydrostatic pressures of its content. When the hydrostatic pressure is high enough to overweigh the gravity and frictional forces of the plug, the expulsion of the plug occurs and drug release starts. The effects of thicknesses of the membrane and plug as well as the concentrations of cellulose acetate and castor oil on the onset of drug release were presented by a polynomial model. It was found that the effect of plug thickness on the onset of release is more important when the membrane is thicker. The results showed that the presence of caster oil in coating formulation (cellulose acetate 10% or 15%) increased the onset of release (to values). The onset of release varied from 0.6 to 10.5 h among which the onset times of 4.2, 4.8, 5.9, 5.5, 7.5, 5.0, 7.8 and 10.5 h could be of use for either chronotherapeutic purposes in protection of patients against heart attacks and strokes during early morning hours or reducing daily frequency of dosage