Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Capsules
Reexamination Certificate
2001-01-24
2003-12-30
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Capsules
C424S472000, C424S453000, C424S464000, C424S466000, C424S468000, C424S470000
Reexamination Certificate
active
06669954
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates generally to drug delivery systems, more specifically, the invention relates to a device and a method for controlling release of pharmaceutical agents.
2. Description of the Related Art
The advantages of controlled release preparations of therapeutic agents are well-established. When a drug release is non-controlled, the concentration of drug available in the bloodstream after administration quickly rises and then declines. It is desirable to maintain more constant drug levels over time, allowing administration of fewer doses per day, making patient compliance more likely and reducing the frequency of swings of drug levels in the patient's system. Controlled release preparations are an important means of avoiding an excessively rapid increase in drug concentration and attendant side-effects. In addition, such preparations prevent the drug concentration from falling below therapeutic levels.
The fundamental parameters that affect the release of drug from a controlled release dosage form include the solubility of the drug, Cs, the effective diffusivity of the drug, D
eff
, and the surface area available for release of the drug from the dosage form, SA.
FIG. 1
illustrates the relationship between these factors where m is mass, t is time, D
eff
is the effective diffusivity, SA is the surface area, Cs is the concentration of drug in solution at the surface of the solid, Cb is the concentration of drug in solution in the bulk, and &dgr; is the thickness of the diffusional boundary layer. While there are numerous adaptations on this theory, such as, osmotic controlled release, polymeric barriers, encapsulation, Cs, D
eff
and SA remain the rate limiting parameters.
In addition to the above analysis, drug release can be controlled using polymeric barriers such as hydrogels. As the hydrogel swells and drug is released, the diffusional boundary layer increases, slowing down the rate of release.
FIG. 2
illustrates this process, where Q is the amount of drug release per unit surface area, D is the diffusivity, A is the total amount of drug loaded into the dosage for, Cs is the solubility of the drug and t is the time. Equation 2 is often referred to as the Higuchi equation and is used to estimate the amount of drug that will be released from a matrix delivery system. T. Higuchi,
J. Soc. Cosm. Chem.
11 (1960) p. 85.
There exists a continuing unmet need for a device and method for controlled delivery which provides simple, inexpensive means of defining release parameters of both water soluble and insoluble pharmaceutically active agents. The present invention controls the release of drug by limiting the surface area available for release and by controlling the length of the diffusion boundary layer.
SUMMARY OF THE INVENTION
The invention provides a device for the controlled release of pharmaceutical agents which includes a coated, apertured container permeable to water that is only semi-permeable to a pharmaceutical agent in the container, a removable aperture cover and an excipient formulation in the container. The invention is also directed to a drug delivery system where the container composition optionally includes a biocompatible polymer. The container may optionally be a hard gelatin capsule. The excipient formulation may include release control components, filling agents and lubricating agents. The drug delivery device may be used to deliver organic, inorganic or organometallic pharmaceutical agents. The container is coated with a covering permeable to water but only semi-permeable to the pharmaceutical agent in the container. The covering may optionally include cellulose acetate. Also provided is a process for drug delivery using the device described.
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Amidon Gordon L.
Crison John R.
Bennett Rachel M.
Gifford, Krass, Groh Sprinkle, Anderson & Citkowski, P.C.
Page Thurman K.
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