GB2180749A

GB2180749A - Delivering biologically active agents

Info

Publication number: GB2180749A
Application number: GB08623087A
Authority: GB
Inventors: Michael T Shepherd
Original assignee: Coopers Animal Health Ltd; Coopers Animal Health NZ Ltd
Current assignee: SP Veterinary Ltd; Schering Plough Animal Health Ltd New Zealand
Priority date: 1985-09-25
Filing date: 1986-09-25
Publication date: 1987-04-08
Also published as: GB8623087D0; GB8523690D0

Abstract

A release unit for delivering an active ingredient, for example into the rumen of a ruminant animal, comprises a support 3 and an annular tablet 5 of e.g. sintered soluble glass containing the active ingredient which fits within the support 3 and is retained there by a boss 7 having radial projections 9, 11 and an orifice 13 through which the active ingredient is released. <IMAGE>

Description

SPECIFICATION Release unit The present invention relates to release units for fabricating devices for releasing substances, especially biologically active substances, into liquid environments.

Many devices have been proposed for administration of biologically active substances to ruminant. animals by direct release into the rumeno-reticular sac. Generally, these comprise a reservoir of the active substance in either unitary or segmented form, in a container which is provided with means to prevent regurgitation, for example suitable weighting or a geometrical feature such as protruding wings. In such devices, the reservoir may comprise the active substance in a liquid or gel form or as a solid formulation.

Solid formulations for this purpose may for example comprise routine tablet compositions formulated to provide the required delivery characteristics. Solid formulations may also in relatively non-conventional form such as a soluble glass (particularly a water-soluble glass) in which the active substance is dispersed. A device of the latter kind is described in European Patent Specification 147,932 A.

To provide very slow release of the active substance we have now found it advantageous to provide a device which comprises one or more agent release units of a particular novel kind.

Thus, according to the present invention we provide a release unit for delivery of a biologically active substance, said release unit comprising a dose unit of the active substance and a support means for the dose unit.

A release unit according to the invention may constitute the entire, or nearly the whole of the required device, or the device may be made from a plurality of such release units, optionally with one or more additional components.

These new release units are especially useful for fabricating devices for intraruminal administration of biologically active substances but are not exclusively limited to that utility.

One advantage of such a release unit resides in that the dose unit is prevented from beng regurgitated and also from being damaged inside the rumen until substantially all of the active substance has been released slowly over the intended time period. The release units may also be used for fabricating devices for the following uses which are intended to be neither exhaustive nor limiting of the scope of the present invention. These devices are those for releasing biologically active substances such as herbicides or pesticides into rivers, ponds, pools, lakes or other bodies of water, those for releasing biologically active substances in vivo into body fluids (other than ruminal fluids) of mammals, including humans and devices for releasing in a predetermined manner, any desired substance into a liquid which takes part in an industrial process.

In case of release units for intraruminal devices, examples of biologically active substances to be contained in the dose unit or units include therapeutic agents (such as anthelmintics), growth promotants (such as of the ionophore type) and trace elements.

The biologically active substance may constitute the whole of the dose unit, or where the nature of the substance makes necessary, is in the form of a composition of the substance formulated together with one or more accessory ingredients. Such accessory ingredients include regular pharmaceutical carriers and excipients for pharmaceutical formulation unit dose forms (such as tablet formulations), soluble glasses including sintered soluble glasses, biodegradable polymers, hydrogel materials, erodable or otherwise degradable metals and metal alloys (such as magnesium alloys) and soluble waxes.

The formulation of the active substance and accessory ingredient(s) may be effected by any appropriate method. For example, when the accessory ingredient is a sintered soluble glass, the active ingredient may be incorporated by admixture with the sintered glass which is then compacted, bonded, part-melted or otherwise caused to be held together in unitary form. Alternatively, the sintered glass alone may be brought into such unitary form and then the active ingredient melted and brought into association therewith in a way such that it can be absorbed into the sintered glass, after which it sets, or by the active ingredient being dissolved in an appropriate solvent which is caused to be absorbed into the sintered glass.In the latter case, the soi- vent is subsequently removed by being allowed to evaporate-off at room temperature or by heating and/or subjection to vacuum conditions as appropriate. Methods for the formulation of pharmaceutical unit dose such as tablets, including those for slow release applications, are well known to those skilled in the art.

It will also be appreciated that if desired, the dose unit of a release unit according to the invention may comprise two or more biologically active substances, optionally formulated together with one or more accessory ingredients.

The present invention will now be illustrated by way of the following particular embodiments and with reference to the accompanying drawings in which: Figure 1 represents in perspective view, a release unit for fabricating an intra-ruminal device.

Figure 2 shows the elements of the unit of Fig. 1 in section, prior to assembly.

Figure 3 shows in section, the assembled elements of Fig. 2.

Figure 4 shows an intra-ruminal bolus fabricated from a plurality of units of the kind shown in Figs. 1-3.

Figure 5 represents an intra-ruminal device comprising a plurality of release units according to the present invention.

A release unit 1 according to the present invention is shown in Fig. 1 and comprises a plastics collar 3 in which rests a dose unit comprising an annular tablet 5 of sintered glass containing a biologically active substance. The tablet is retained by a boss 7 having radial projections 9, 11. The boss is provided with an orifice 13 through the centre thereof. The collar is provided with an annular shoulder 14 for receiving a sealing washer.

Fig. 2 shows the collar, tablet and boss prior to assembly and Fig. 3 shows these components in assembled form.

Fig. 4 shows an intra-ruminal bolus comprising a plurality 15, 17 or release units of the kind shown in Fig. 1 held together by an interference fit on magnesium alloy rod 19 which is also held by interference fit in cavity 21 in steel endweight 23 to prevent regurgitation. A plurality of resilient plastics washers 24 are provided to effect a liquid impermeable seal betwen adjacent release units. However, it will be appreciated that the washers may be omitted if the collars of the units are sufficiently resilient in themselves. In use, the radial projections of the units prevent the tablet from fall away from the respective unit until substantially all of the tablet contents have been released. After (say) 15-20 days, galvanic corrosion of the alloy rod progresses sufficiently for the first unit to fall away from the body of the bolus, whereupon the unit and any tablet remains are regurgitated.

Fig. 5 shows an alternative intra-ruminal bolus 25 comprising a plurality of release units 27, 29 according to the present invention.

These units, each comprise an annular sintered glass tablet 31 containing a biologically active substance. The tablet is held in a support 33 of a suitable substance, for example a wax or a consolidated soluble glass. It will be seen the latter substance is poured in molten form around the tablets, for example in a suitable mould, and allowed to set. Thus the supports of adjacent units are contiguous. If necessary, appropriate weighting means is provided to prevent reguritaion.

Claims

1. A release unit for delivery of a biologically active substance, the release unit comprising a dose unit of the active substance and a support means for the dose unit.

2. A release unit according to claim 1 comprising a plurality of support means and dose units.

3. A release unit according to claim 1 or 2 wherein the dose unit comprises the active substance dispersed in a water-soluble glass.

4. An intra-ruminal device comprising a release unit according to any one of claims 1 to 3.

5. A release unit substantially as described herein with reference to the accompanying drawings.