Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Capsules
Patent
1994-08-16
1995-12-05
Page, Thurman K.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Capsules
424458, 424464, 424462, 424474, A61K 948
Patent
active
054727081
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
My invention relates to controlled absorbtion drug delivery systems and more particularly to combined coating dissolution and explosion mechanisms in coated drug-containing pellets for assured timely release of orally administered pharmaceuticals.
BACKGROUND ART
A unique sustained-release drug delivery system, Time-Controlled Explosion System (TCES), was described in U.S. Pat. No. 4,871,549 issued Nov. 3, 1989 to Ueda et al. Drug release is caused by explosion of an insoluble, water permeable membrane after a definite period of time. Beads or granules contain the drug and a swelling agent enclosed by the water insoluble membrane. Water permeates the membrane and causes the swelling agent to expand until the internal forces on the membrane cause it to burst or explode, thereby releasing the drug. This mechanism is especially useful with water insoluble drugs in which those prior art delay mechanisms related to diffusion of the drug through a permeable coating would not be effective.
A remarkable feature of the TCES is that drug is not released from the completely coated pellets or spheres until the membrane bursts, and then it is all available. This can provide for a pulse of drug release. The lag time before release is related to the thickness of the membrane with maximum lag times of approximately four hours reported by Ueda.
One of the principal uses for delayed release forms of medication is to provide for a once a day oral administration that releases drug in a continuous controlled rate or in a series of sequential pulses throughout the 24 hour period. This ensures a reasonably uniform blood level for maximum efficacy with the least toxic effect from high peaks of blood concentration. This is not easily accomplished with the system of Ueda because the insoluble membrane must be made very thick for long delays,and this makes explosion less reliable. If the membrane never bursts, the drug will be lost in the stool and the patient will get less drug than prescribed and never be aware of it. Furthermore, in cases where there is a delayed stomach emptying time, much of the explosion may take place in the stomach and not be available for absorbtion until the pyloric sphincter opens. This may present a very large dose for sudden absorbtion that may be very dangerous. Furthermore, acid unstable drugs should not be released to the acidic stomach contents, where an indeterminate portion of the drug dose may be destroyed.
DISCLOSURE OF THE INVENTION
It is accordingly an object of the invention to provide unit dosage forms for drugs or therapeutic agents that will release the drug into the environment of use in a series of sequential, pulsatile releasing events that employs conventional pharmaceutical equipment and products such as roller compaction methods for optimum economy, reliability and bioavailability. It is another object to provide dosage units readily adaptable to a variety of timing intervals, different therapeutic agents and combinations of agents, including agents which cannot be released by diffusion through an insoluble coating. It is yet another object to provide a system that can yield a large number of pulses within a single unit dosage form at no significant increase in cost over only one or two pulses. It is yet another object of the invention to provide means for protecting the drug from adverse environmental conditions prior to delivery into the environment of use. It is yet another object of the invention to provide a drug delivery system in which the explosive pellets mechanism for drug release is modified by changing the coating to delay the explosion event in a more controllable and reliable fashion than simply increasing the thickness of the insoluble coating.
The coating of the invention is provided with two means to alter release time of the drug. A first means for altering of the invention comprises the incorporation of a water soluble polymer along with the insoluble, water permeable coating material of the prior art. This water soluble polymer is of the ente
REFERENCES:
patent: 4716041 (1987-12-01), Kjornaes et al.
patent: 5017381 (1991-05-01), Maruyama et al.
patent: 5110597 (1992-05-01), Wong et al.
patent: 5213808 (1993-05-01), Bar-Shalom et al.
Andrx Pharmaceuticals Inc.
Benston, Jr. William E.
Blum Alvin S.
Page Thurman K.
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