Delayed, sustained-release pharmaceutical preparation

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The preferred delayed, sustained-release pharmaceutical preparation of the present invention is a water soluble core drug surrounded by a hydratable diffusion barrier comprising an insoluble film-forming polymer such as Eudragit NE30D (Rohm Pharma) and an additive which controls the rate of hydration and permeability of the diffusion barrier, together in microparticle form.
The core drug is preferably a soluble orally administered drug which provides sustained release over periods of 4 to 24 hours.
The solubility of the drug in the intestines should be greater than 10 grams per liter as drugs with lower solubility will not dissolve and diffuse through the hydrated diffusion barrier at adequate rates.
Examples of suitable drugs include propranolol hydrochloride, guinidine gluconate, diltiazem hydrochloride, dextromethorphan hydrobromide, diphenhydramine hydrochloride, disopyramide phosphate, and verapamil hydrochloride.
The hydratable diffusion barrier is formed by combining the film-forming polymer and additives which control the rate of hydration and permeability of the diffusion barrier, and then spray coating the core drug.
As mentioned previously, the film-forming polymer may comprise Eudragit NE30D while the additives may include Eudragit RS30D and RL30D.
The Eudragit RS30D and RL30D are aqueous dispersions of film-forming polymers, and may be combined with the insoluble film-forming polymer in any proportion to achieve the desired permeability.
Preferably, when mixing the film-forming polymer such as Eudragit NE30D with additives such as Eudragit RS30D and RL30D, an anionic surfactant is added to the NE30D in an amount of about 1% to prevent the dispersions from becoming unstable.
Thus, in the most preferred embodiment, the additive is a mixture of materials used to achieve the desired hydration and permeability of the diffusion barrier.
In one embodiment, the additive comprises from about 3 to 50% of a fully esterified acrylic resin suspension containing quaternary amine side chains such as Eudragit RS30D or RL30D, from about 0 to 1% sodium lauryl sulfate, from about 10 to 20% magnesium stearate, and from about 40 to 87% water