Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Capsules
Reexamination Certificate
1994-12-15
2001-03-13
Bawa, Raj (Department: 1619)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Capsules
C424S422000, C424S457000, C424S463000, C424S487000, C424S488000
Reexamination Certificate
active
06200600
ABSTRACT:
This invention relates to novel devices for the controlled release of active materials, especially pharmaceutical drugs to an aqueous medium. More particularly this invention relates to devices which are adapted to release their contents over a relatively short period following a controlled delay after administration—a pulsed release device.
BACKGROUND OF THE INVENTION
A wide variety of devices for the controlled release of drugs have been proposed. These dosage forms which may be termed “sustained release”, “timed release”, “prolonged release” or “controlled release” forms are designed to dispense the drug in a controlled reproducible manner. Previous attempts to provide release in a short burst over a period of the order of minutes e.g. those described in U.S. Pat. No. 3,952,741 have not been successful in controlling the delay before which the pulsed release of active material occurs.
DESCRIPTION OF THE INVENTION
He have now discovered a novel device which provides a sharp pulsed release after a predetermined reproducible delay following administration. Furthermore in a preferred embodiment the devices of this invention combine or utilise this release profile with the controlled release of active material over the period before and/or after the sharp pulsed release.
From one aspect our invention provides a controlled release device comprising a water permeable capsule containing at least one active material which is characterised in that the wall of said capsule is formed from at least two separable pieces and said capsule contains a water sensitive material which when wet will cause a positive pressure to be exerted on the interior wall of the capsule and result in the separation of the two pieces.
The capsule may be formed in any convenient shape for example spheroidal, ellipsoidal or cylindrical. Capsules which are generally cylindrical are preferred.
The walls of the capsule may be formed from any material which is biologically and medically compatible, non allergenic, insoluble in and non-irritating to body fluids and tissues. In the preferred embodiment at least a part of the wall is formed from a water permeable material.
In a preferred embodiment a first piece of the wall of the capsule defines at least one orifice which orifice is closed by a second separable piece which Is a plug. The first piece may take the form of a generally cylindrical tube closed at one end and open at the other, the open end defining an orifice.
In another embodiment a first piece of the wall defines more than one and preferably two orifices. A suitable first piece is a generally cylindrical open ended tube wherein each end of the tube may be regarded as defining an orifice. The two orifices may be closed by suitable plugs thus defining a capsule.
The walls of the capsules may be formed in part from a water impermeable material or materials. They may be of uniform or laminar construction. They may take the form of an impermeable coating applied to the surface of a water permeable material from a water impermeable material or materials. Indeed such a construction represents a preferred embodiment since it facilitates the control of the rate of ingress of water into the interior of the capsule.
The capsule is constructed in such a manner as to control the rate of ingress of water into the interior of the capsule. The rate of ingress is affected by the permeability of the material or materials from which the capsule is constructed, the thickness of the walls of the capsule and the surface area of the capsule. Altering the surface area of the water-permeable section of the capsule wall represents a convenient method of controlling the rate of ingress of water. The capsule is constructed and filled in such a manner as to control the delay following the initial exposure of the device after which the water sensitive material comes into contact with an aqueous medium. The length of the delay may be varied through a wide range. Delays of 0.5 hours may be useful in some applications, whereas delays of up to seven days may be useful in others. More usually the devices may be constructed so as to provide delay times of from 1 to 12 hours, more usually from 4 to 8 hours. Such devices are of particular value in oral dosage forms.
This control may be achieved in a variety of ways dependent upon the delay which is required. Where the second separable piece, i.e. the plug is of such a size and constructed of such a material that the flux of water through the plug alone is sufficient then the first separable piece, i.e. the walls may be and preferably is constructed from a water impermeable material such as a plastic. Where a greater influx of water is desired the walls of the capsule may be constructed entirely from a water permeable material or materials. Where the walls of the capsule define an orifice which is closed with a plug the closure should be substantially watertight. The plug may be formed from a water swellable material so that in use the swelling may contribute to the separation of the plug and will assist in retaining a water tight seal.
It will be appreciated from the above that there are a number of factors which affect the length of the delay between the initial exposure of the device to an aqueous medium and the release of the active material. The dimensions of the plug may be used to vary the delay time. The plug is preferably cylindrical but may adopt other geometries such as cone sections. In particular in the preferred embodiment utilising a cylindrical plug the delay is proportional to the length of the plug. The position of any plug may also be utilised to regulate the delay time. In particular where the outer surface of the plug is recessed so as to lie below the level of the mouth of the orifice the ejection of the plug will be delayed by a time which is a function of the depth of the recess. In a preferred form the device is preferably constructed so as to facilitate the positioning of the plug by the provision of a retaining means, e.g. a ridge or ledge on the interior face of the orifice at an appropriate depth. The plug is then inserted so as to engage this means which is sufficiently wide to prevent the plug penetrating to a greater depth. The nature of the materials used to construct the capsule and the thickness of those materials can all affect the length of this delay. The dimensions of the plug may vary according to the size and intended application of the device. For devices intended for use as oral dosage forms in man the plugs will typically have a length of from 1 to 5 mm. Where they are recessed so as to lie below the surface of the capsule, the recession will generally be no more than 3 mm and preferably no more than 2 mm. In practice the delay may be adjusted empirically for any particular device until the desired delay is achieved. It is a feature of the devices of the present invention that the delay times for particular devices are reproducible to a high level of accuracy.
The capsule preferably comprises only one orifice which extends from its exterior to its interior. The hollow capsule may be preformed and a hole subsequently drilled from the exterior into the hollow interior or alternatively the capsule may be formed with an orifice, e.g. by forming a cylinder around a rod. The capsule may be formed by coating a solution of a soluble polymer or an organosol onto a former, by compression or injection moulding of a suitable thermoplastic polymer, by powder compression or by direct reaction moulding. Capsules of particular utility in the devices of the present invention are those which take the form of a cylindrical capsule closed at one end and open at the other which may be formed by moulding a polymer around the ends of a rod or from extruded plastic tube cut into lengths and preferably sealed at one end.
The interior of the capsules of this invention contains at least one water sensitive component and at least one active material. The contents preferably fill the interior of the capsule and if necessary other materials such as inert excipient may be intro
Bawa Raj
BTG International Limited
Nixon & Vanderhye
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