WO1994009744A1

WO1994009744A1 - Capsule cap

Info

Publication number: WO1994009744A1
Application number: PCT/GB1993/002269
Authority: WO
Inventors: Howard Norman Ernest Stevens; James Leonard Mackie
Original assignee: R.P. Scherer Corporation
Priority date: 1992-11-05
Filing date: 1993-11-04
Publication date: 1994-05-11
Also published as: EP0692956A1; AU5426094A; JPH08505370A; CA2148456A1; GB9223148D0; KR950703924A

Abstract

A cap (8) for fitting to the body (6) of a capsule for delivering a dose of pharmaceutically active material has a tubular open end portion (20) and a domed closed end portion (26). To avoid jamming of the caps one-inside-another whilst being fed within a capsule filling machine, the external diameter of the domed end portion exceeds the internal diameter of the mouth (22) of the tubular open end portion. The taper of the cap may be reduced compared to conventional caps, and the wall thickness may be increased. An inwardly extending ring (28) may be provided near the mouth of the tubular portion. The domed end portion is preferably flattened and non-hemispherical.

Description

CAPSULE CAP

TECHNICAL FIELD

The present invention relates to a cap for fitting to the body of a capsule for containing a pharmaceutically active material. In particular, though not exclusively, the cap is for use with a controlled release capsule construction which comprises a male plug engaged within a neck of a female body; the male plug being formed of a water-swellable material which swells so as to disengage the female body upon exposure to an aqueous medium.

BACKGROUND

International Patent Specification WO 90/09168 discloses a capsule of this type which comprises a water swellable male plug engaged within a female body. A pharmaceutically active material is contained within tr_= device. When the capsule is exposed to water, the male hydrogel plug swells and eventually disengages itself from the female body, thereby allowing the pharmaceutically active material contained within the capsule to be released. It has been found that the time taken to release the pharmaceutical materiε.1 is predictable and reproducible, so that the device may be used to release pharmaceutically active material within the body of a patient after a predetermined time interval. This may, for example, be useful in the treatment of medical conditions where it is desirable to administer a pharmaceutically active material to the patient sometime through the night while the patient is asleep, so as to provide a desired level of the drug in the patient in accordance with his needs, for example during the night or when he awakes. It may also be useful to allow dosing of materials at a predetermined point as the capsule passes through the gastro-intestinal tract, for example in the colon.

Conventional hard gelatin capsules are produced and filled in large numbers using high speed automatic machinery. Such capsules comprise a body and a cap. Normally the cap is pre-fitted to the capsule body during manufacture of the capsule. During filling, the filling machine removes the cap, fills the capsule with pharmaceutical material, and then replaces the cap - often in a manner such that the cap is locked onto the capsule body. Patent Specification U.S. 3,399,803 discloses a self-locking medicament capsule wherein the body has a groove near its open end, and the cap has a corresponding ridge which snaps into the groove so as to lock the cap and body together. U.S. 4,442,941 discloses a bayonet-type arrangement whereby a raised portion on the cap is engaged into a groove on the body.

European Patent Specification 246804 also discloses a capsule body having a groove near its mouth for the purposes of preventing the capsule distorting from its cylindrical form, which may cause difficulty in fitting the cap onto the capsule body.

However, in the type of controlled release capsule construction disclosed in WO 90/09168 it may be inconvenient to employ pre-locked cap/body assemblies, since in a filling machine a number of steps are required to be carried out between the disengagement of the pre-locked assemblies and their reassembly. It would therefore be convenient to provide the caps and the bodies separately within the filling machine for subsequent assembly as part of the filling process. However, conventional caps have a tendency to nest and jam one inside another dur - ~ storage, and more particularly as the caps are directed sequentially down a chute in a filling machine. One reason for this is that the caps are not truly cylindrical but taper slightly (i.3. are frustro-conical) from a wider open end to a .-.arrower hemispherical end. The degree of taper is slight and is intended to assist removal of the c~.~ from its mould during production. Typically the caper is about 0.012 inch (304 microns) , that is to say the radius at the upper end of the frustro-conical section adjacent the hemispherical end is 0.012 inch less than the radius at the open end of the cap. However, this taper may be sufficient to allow the hemispherical end of one cap to get jammed inside the open end of ar. adjacent cap.

It is an object of the present invention to mitigate this problem by providing a cap construction wherein jamming together of the caps is minimised.

SUMMARY OF THE INVENTION

Thus, the present invention provides a cap for fitting to a body of a capsule, the cap having a tubular open end portion for engaging the capsule body and a domed closed end portion; the domed closed end portion having an external diameter greater than the internal diameter of the tubular open end portion, such as to substantially avoid interlocking of nested caps.

Generally speaking, this may be achieved in one of a number of wayε ; or some or all of them in combination. Firstly, the taper of the cap can be reduced compared to conventional caps. Secondly, the wall thickness of the cap can be increased. Thirdly, an inwardly extending protrusion or protrusions may be provided adjacent the mouth ~f the open end portion.

According to the first provision the taper may be reduced. Conventional substantially cylindrical caps generally have a taper such that the radial width of the cap reduces slightly from the open end to the closed end. This taper assists removal of the cap from its moulding pin during production of the cap. Usually, this taper is of the order of 300 microns. In an embodiment of the invention, the taper is reduced to no more than 250 microns. This has the effect of increasing the external radius of the domed portion relative to the internal radius of the tubular end portion. The taper is the difference between the radius of the domed end portion and the radius of the mouth of the tubular portion.

Secondly, the wall thickness may be increased. In order to increase the difference between the internal diameter of the mouth of the tubular open end portion and the external diameter of the domed portion, it is preferred to increase the wall thickness (over that conventionally used) such that the wall thickness is at least 200 microns, (e.g. 220 to 280 microns) . A conventional hard gelatin cap has a wall thickness of approximately 0.005" (127 microns).

According to a third provision, an inwardly extending protrusion or protrusions may be provided adjacent the mouth of the open end portion, such as to further minimise any tendency to nesting and jamming. The protrusions may be individual protrusions or the protrusions may together form a continuous inwardly extending ridge.

In one embodiment -he cap is wider at its domed end than its open end; the transverse external diameter of the domed end portion exceeding the transverse external diameter of the open end portion, usually by up to 5% of the diameter.

Advantageously, the domed end of the cap may be flattened relative to conventional hemispherical caps so as to increase the angle between a tangent at a position on the domed end where the domed end meets an adjacent cap, and the inside wall of the adjacent cap when nested thereto. In particular, the minor radius of the flattened dome may be from 60 to 80% of the major transversely extending radius (i.e. in the direction transverse to the longitudinal axis of the tubular open end portion) . The flattened dome may be substantially hemi-ovoid in shape or it may be a similar non-geometrically defined shape. Thus, the terms "radius" and "diameter" as used herein are not used in a strict geometrical sense but in a general sense.

Another aspect of the invention relates to a capsule comprising the cap fitted to a capsule body. In a preferred arrangement, the capsule body has a reduced diameter neck region adjacent the open mouth of the body, and the cap has an inwardly extending ridge between the tubular open end portion and the domed portion, the ridge being engaged within the ^.εc region of the body to lock the cap to the body.

A further aspect of the invention provides a method of filling the capsule, which comprises;

(i) providing a supply of the caps and a separate suDply of capsule bodies;

(ii) feeαing a body to a filling location and introducing a unit dose of pharmaceutically active material into the body; and

(iii) closing the capsule by fitting a cap over an open end of the capsule. The method may further comprise the step of introducing a plug of a water swellable material into a neck of the filled capsule body prior to fitting the cap thereto. Preferably the capsule body has a flared outwardly extending open mouth and the cap has inwardly extending protrusions, and the method comprises the further step of pressing the cap onto the body such that the inwardly extending protrusions clip over the flared mouth of the body to lock the cap in place on the body.

The present invention is particularly applicable to a controlled release capsule which comprises a male plug engaged within a neck portion of a female bc y; the male plug being substantially cylindrical and formed from a water-swellable material which swells so as to disengage the female body upon exposure to an aqueous medium. The water swellable material is preferably as disclosed i -. W090/09168.

DETAILED DESCRIPTION OF PREFERRED EMB DIMENTS

Embodiments of the present invention will now be described by way of example only with reference to the drawings wherein;

Figure 1 is a cross sectional elevation of a first embodiment;

Figure 2 is a schematic elevation of a series of caps in the chute of a capsule filling machine;

Figure 3 is an elevation of a second cap construction; and Figure 4 is a part cross sectional elevation of a series of caps according to the second construction in a filling machine chute.

The capsule shown in Figure 1 comprises a male plug 2 formed of a hydrogel material inserted in neck 4 of female body 6. The capsule is closed with a cap 8. Typically, a size "0" capsule size is employed.

The body 6 comprises a cylindrical main portion 10 and closed end 12. The main body narrows to the neck portion 4 which is substantially cylindrical so as to receive the male plug 2 with a close tolerance. The neck portion then flares out to a flared mouth portion 14 of a diameter substantially the same as the diameter of the main body portion 10.

The cap 8 comprises a tubular (substantially cylindrical) open end portion 20 having a mouth 22, and at its inner end a ridge 18 or series of detents for locking the cap onto the body and a stop ring 24 for locating the cap on the body. The cap has a domed closed end 26 which is flattened relative to a hemisphere. In the embodiments shown, the upstanding radius (along the longitudinal axis of the tubular open end portion) is approximately 70% of the transverse radial direction. This flattening helps avoid jamming of the nested caps by increasing the angle between the dome and the mouth of an adjacent cap when nested thereto. The cap wall thickness is substantially 250 microns. In the embodiments shown, the domed portion extends outwardly slightly beyond the tubular open end portion.

The male plug 2 is formed of a hydrogel material (such as disclosed in WO 90/09168) and is usually inserted so that the upper end of the plug is level with or below the upper end of the capsule body.

The cap is formed of a water soluble material, such as gelatin. The capsule body is formed of a water insoluble material, which may be a water insoluble plastics material or may be gelatin coated with a water-impermeable coating.

The capsule body is formed in conventional manner by dipping a mould pin into a gelatin solution and allowing to dry. The gelatin is then coated with a water-impermeable coatir.g (e.g. by dip-coating) after the capsule body is stripped from the mould pin and trimmed to size. Alternatively, the water-impermeable coating may JC3 applied by spray coating or vapour deposition onto the capsule body.

The walls of the female body may be formed from a wide variety of materials. They may be of homogenous constructions or they may be laminated. Examples of materials suitable for use in the construction of the body include polyethylene, polypropylene, poly(methylmethacrylate) , polyvinyl chloride, polystyrene, polyurethanes, polytetrafluoroethylene, nylons, polyformaldehydes, polyesters, cellulose acetate and nitro cellulose. However, a preferred construction uses an impermeable coating to cover the exterior of a body which has been formed from a water soluble material. The coating may conveniently be formed by dipping the body in a solution of a material which forms a layer which is impermeable to water. Alternatively, the body might be spray-coated. A preferred class of capsule bodies are conventional hard gelatin or starch capsule bodies coated with a solution of polyvinyl chloride or a polyvinyl acetate copolymer or an ethyl cellulose solution.

Figure 2 shows three nested caps 8 travelling down a delivery chute 30 in a filling machine, prior to being fitted onto the capsule body. During assembly, the capsule body is first filled with pharmaceutically active material. Then, the hydrogel plug is positioned in the neck cf the body and inserted into the body so as to be locate! correctly (usually either flush with the top of the body or slightly recessed) . Finally, the cap is fitted over the mouth of the capsule body to form the assembled capsule as shown in Figure 1.

Figure 3 shows a second embodiment which is generally similar to the first embodiment, analogous parts being labelled with the same reference numerals, but with the addition of a further ring 28 adjacent the open mouth 22 of the open ended portion 20 of the cap. As can be seen ₍ in Figure 4, this helps further assist prevention of jamming together of the nested caps in the filling chute. The ring 28 locates at the lower end of the neck 4 (see Figure 1) when the cap is fitted onto the body.

Depending on the intended application, the cap may be enteric coated to prevent dissolution in the stomach. In the higher pH of the intestine the enteric coating dissolves exposing the water soluble cap, which in turn dissolves in the aqueous medium. The enteric coating may be any coating material known in the art, such as those disclosed in WO 90/09168.

As used herein, the term enteric coating includes all coatings (whether pH dependent or not) which are able to pass through the stomach and dissolve in the intestine. This includes coating materials, such as fats, which dissolve preferentially under the enzymatic regime prevailing in the intestine.

Claims

A cap for fitting to a body of a capsule, the cap (8) having a tubular open end portion (20) for engaging the capsule body and a domed closed end portion (26) ; the domed closed end portion having an external diameter greater than the internal diameter of the mouth (22) of the tubular open end portion, such as to substantially avoid interlocking of nested caps.

A cap according to claim 1, wherein the domed closed end portion is flattened, such as to be non-hemispherical, and have a major radius extending substantially transversely to a longitudinal axis of the tubular open end portion, and a minor radius extending substantially along said longitudinal axis.

- zap according to claim 2, wherein the minor radius of the flattened dome is from 60 to 80% of the major transversely extending radius.

A cap according to any preceding claim wherein the transverse external diameter of the domed end portion exceeds the transverse external diameter of the tubular open end portion.

5. A cap according to any of claims 1 to 3 wherein the transverse external radius of the domed end portion is less than the external radius of the mouth of the tubular open end portion by no more than 250 microns.

6. A cap according to any preceding claim wherein the wall thickness of the tubular open end portion is at least 200 microns.

7. A cap according to any preceding claim which further comprises an inwardly extending protrusion or protrusions (28) adjacent the mouth of the tubular open end portion.

8. A cap according to claim 7 wherein the protrusion is in the form of a continuous inwardly extending rinσ (28) .

9. A capsule which comprises a cap according to any preceding claim, fitted to a capsule body (6) .

10. A capsule according to claim 9 wherein the capsule body has a reduced diameter neck region (4) adjacent the open mouth (14) of the body, and the cap has an inwardly extending ridge CIS) between the tubular open end portion and the αomed portion, the ridge being engaged within the necked region of the body to lock the cap to the body.

11. A capsule according to claims 10, 9, 8 and 7 wherein the protrusion(s) (28) adjacent the mouth of the tubular open end portion is/are also engaged within the neck region (4) of the body.

12. A capsule according to claim 10 or 11 which further comprises a plug (2) of a water-swellable material inserted in the neck region (4) of the capsule body.

13. A method of filling a capsule according to claim 9, which comprises;

(i) providing a supply of said caps and a separate supply of said capsule bodies; (ii) feeding a body to a filling location and introducing a unit dose of pharmaceutically active material into the body; and (iii) closing the capsule by fitting a cap over an open id of the capsule.

14. A method according to claim 13 which comprises the further step of inserting a plug of a water-swellable material into the neck region of the capsule body, prior to fitting of the cap.