Controlled delivery devices

A device for controllably delivering a material into an aqueous medium, the device comprising a soluble portion which is adapted, in use, to dissolve in an aqueous medium thereby to deliver into the aqueous medium a material which is retained in the device, the soluble portion comprising a soluble phosphate glass having a P.sub.2 O.sub.5 content of from 40 to 50 mole %, and constraining means which are located in the vicinity of the soluble portion and which are arranged, in use, to constrain a stationary liquid layer between the soluble portion and the constraining means. The invention also relates to a method of controllably dissolving a soluble phosphate glass in an aqueous medium.

BACKGROUND OF THE INVENTION 
This invention relates to a device including a portion of phosphate glass 
which can be controllably dissolved to perform a function, for example to 
release controlled quantities of an active material into an aqueous 
environment at or after a pre-determined time interval. The invention also 
relates to a method for controlling the dissolution of a phosphate glass. 
There is a need for the release of active materials such as drugs or 
pesticides into an aqueous environment at or after a pre-determined time 
after being placed in contact with the aqueous environment, or 
continuously at a predetermined rate. It is known to employ glasses which 
act as a barrier between the aqueous environment and the active material 
and which dissolve in the aqueous environment over a period of time 
thereby to release the active material at or after a pre-determined time 
Period. It is also known to employ such glasses which themselves 
incorporate the active material. Previous work in this field includes the 
work reported in UK-B-2057420 which dealt with the overall control of the 
dissolution of glasses and exemplified phosphate glasses with a P.sub.2 
O.sub.5 content in excess of 50 mole %. 
The glasses disclosed in UK-B-2057420 suffer from the disadvantage that 
controlled dissolution of the glasses is not possible since, for glass 
compositions having greater than 50 mole % P.sub.2 O.sub.5, the solution 
products are hindered from leaving the glass surface because there is a 
tendency for gelatinous films to form adjacent to the glass surface. The 
gelatinous films interfere with the dissolution of the glass and render 
the dissolution rate time - dependent i.e. the dissolution rate decreases 
with time. This means that the dissolution of the glass cannot be reliably 
controlled. 
SUMMARY OF THE INVENTION 
It is an aim of the present invention to enable reliably controlled release 
of an active material by controlled dissolution of a Phosphate glass. 
Accordingly, in one aspect the present invention provides a device for 
controllably delivering a material into an aqueous medium, the device 
comprising a soluble portion which is adapted, in use, to dissolve in an 
aqueous medium thereby to deliver into the aqueous medium a material which 
is retained in the device, the soluble portion comprising a soluble 
phosphate glass having a P.sub.2 O.sub.5 content of from 40 to 50 mole %, 
and constraining means which are located in the vicinity of the soluble 
portion and which are arranged, in use, to constrain a stationary liquid 
layer between the soluble portion and the contraining means. 
In a second aspect, the present invention provides a method of controllably 
dissolving a soluble phosphate glass in an aqueous medium, the soluble 
phosphate glass having a P.sub.2 O.sub.5 content of from 40 to 50 mole %, 
the method comprising disposing the soluble phosphate glass in the aqueous 
medium and locating constraining means in the vicinity of the portion 
thereby to constrain a stationary liquid layer therebetween. 
The present invention is based on the discovery (a) that glasses containing 
from 40 to 50 mole % P.sub.2 O.sub.5 dissolve in a controllable manner at 
certain concentration ranges of the dissolution products in the aqueous 
medium and (b) of the need to retain a uniform stationary layer of the 
aqueous medium at the dissolving surface from which solution products may 
diffuse in a controlled manner. This means that the devices according to 
the invention can take many forms so long as this basic requirement of the 
provision of a stationary liquid layer is met, and the phosphate glass 
used has a P.sub.2 O.sub.5 content in the range from 40 to 50 mole %.

DESCRIPTION OF THE PREFERRED EMBODIMENTS 
In the devices of each of the three illustrated embodiments of the present 
invention, there is provided a specific means to retain a stationary 
liquid layer of controlled thickness adjacent to at least a portion of the 
soluble phosphate glass. In the following description of the embodiments 
of FIGS. 1 to 3, the means to retain the stationary liquid layer are 
initially described. The theory underlying, and the experimental data 
evidencing, the advantages of the present invention are subsequently 
described. 
FIG. 1 shows a form of a device in accordance with a first embodiment of 
the present invention in which a glass disc 1 is retained within a 
container 2 by means of a spring-clip 4 which transmits pressure via a 
washer 5 thereby to press the glass disc 1 between two elastomeric O-rings 
6 against the shoulder 7 in the container 2. The container has an end wall 
3. The glass disc 1 is composed of a soluble phosphate glass having a 
P.sub.2 O.sub.5 content of from 40 to 50 mole %. O-rings 6 form a 
water-tight seal between a space 8 and body 9 of the container 2 which 
contains the agent 10 to be released. The glass disc 1 initially acts as a 
barrier between the agent 10 and the exterior of the device. As will be 
described hereinafter, the glass disc 1 is slowly dissolved by an aqueous 
medium in which the device is, in use, disposed. The end wall 3 of the 
container 2 is provided with holes 11 which allow diffusion of liquid and 
dissolution products from the space 8 next to the glass disc 1 to the 
exterior of the device and the end wall 3 acts to maintain a stationary 
liquid film between the end wall 3 and the glass disc 1 in which the 
concentration of dissolution products is maintained within a predetermined 
range. The dimensions of the upper O-ring 6, the washer 5 and the clip 4 
are selected to give the desired thickness of stationary layer above the 
glass disc 1. Liquid and dissolution products can diffuse into the body of 
the liquid exterior of the device through the holes 11. The space 8 may be 
filled with filter paper which forms a permeable membrane which assists in 
ensuring that a stationary liquid film is maintained above the glass disc 
as it dissolves. 
The devices of the present invention are of particular value in the pulsed 
release in ruminant animals of various materials which must otherwise be 
dispersed in the animals feed or supplied by periodic drenching or 
injection. Such active materials include anthelmintics and growth 
promoters. Many of these materials are insoluble in aqueous media and are 
therefore difficult to disperse uniformly in a feed mix. They must also be 
released in pulsed doses so that only sufficient material is released in 
the animal for its immediate needs. 
In use, the device initially contains an active material such as an 
anthelmintic (i.e. a composition for killing worms in the rumen of 
ruminant animals). The device is inserted into the rumen of the animal, 
e.g. by swallowing. The water-based medium in the rumen surrounds the 
device and enters the space 8 through the holes 11. The glass disc 1 
slowly dissolves into the aqueous medium in the stationary liquid layer so 
formed. The stationary liquid layer permits a controlled concentration 
gradient of dissolution products of prescribed thickness to be established 
which, in combination with the particular concentration of P.sub.2 O.sub.5 
in the glass being from 40 to 50 mole %, enables a substantially uniform 
dissolution rate of the material of the glass disc into the stationary 
liquid layer over a Period of time. After a prescribed period has elapsed, 
the glass disc is perforated as a result of the dissolution thereof 
thereby releasing the active material into the rumen of the animal. 
FIGS. 2a, 2b and 2c show a device in accordance with a second embodiment of 
the Present invention in which a pair of half cylinders 21 and 22 are 
connected by a flat hinge 23 made of resilient material so that the pair 
of cylinders may be folded together into the configuration shown in FIG. 
2c for insertion into the rumen of an animal. Typically, the 
half-cylinders 21 and 22 and the hinge 23 are composed of an integral body 
of moulded plastics. The half cylinders 21, 22 may be held in the 
configuration shown in FIG. 2c by restraining means 24 which surround a 
portion of the half cylinders 21, 22 and which in the rumen environment 
are released e.g. by degradation to allow the device to return to the open 
configuration shown in FIGS. 2a and 2b. The restraining means may be or 
comprise any material which is dissolved, destroyed, ruptured or broken in 
the rumen environment. Suitable materials include gelatin string or 
gelatin tape. Alternatively, the restraining means may comprise water 
soluble adhesives. 
Each half cylinder 21, 22 is provided with a respective longitudinal 
passageway 25, 26 into which a sealed glass tubule or sealed glass 
capillary 27 filled with active material is placed. The glass of the 
tubule or capillary has a P.sub.2 O.sub.5 content ranging from 40 to 50 
mole %. A longitudinal edge of each passageway 25, 26 is disposed in the 
flat longitudinal surface 28, 29 of the respective half cylinder 21, 22 
thereby to provide a respective continuous longitudinal slot 30, 31 in 
each half cylinder 21, 22 which allows access of the rumen fluid to the 
glass of the tubule or capillary enclosing the active material 33. A 
stationary liquid layer 34 is formed in the vicinity of the line of 
contact between the tubule or capillary 27 and the edge 35, 36 of the 
slots 30, 31 where there is free access to the rumen fluid along the slots 
30, 31. This means that dissolution of the glass of the tubule or 
capillary occurs in a controlled manner in the region of the stationary 
liquid layer and when the wall of the tubule or capillary is dissolved 
away, the active material can easily flow out of the passageway. Although 
rumen fluid can also enter the passageway 25, 26 via a free open end 37, 
38 thereof so as to lie behind the tubule or capillary, controlled and 
preferential dissolution of the soluble phosphate glass occurs in the 
region of the stationary liquid layer. 
The tubules placed in the passageways can be made with a portion of their 
walls of a smaller thickness than elsewhere and the tubules positioned so 
that that portion is placed above the opening of the respective slot. This 
enables precise control over the release of the active material. In order 
to obtain pulsed release of e.g. an anthelmintic, tubules or capillaries 
chosen to release after different elapsed times by having different glass 
compositions or thicknesses may be placed in one or more devices. 
FIG. 3 shows a device in accordance with a third embodiment of the present 
invention. The device consists of a sealed glass tubule 40 of soluble 
phosphate glass having a P.sub.2 O.sub.5 content of from 40 to 50 mole % 
and enclosing an active material 41. A pair of rubber bands 42 (or washers 
or grommets) is placed around the tubule 40. Each rubber band 42 is about 
5mm wide and is placed with its centre about 8mm from a respective end 43, 
44 of the tubule 40. In use, the tubule 40 is received in a respective 
passageway 25, 26 of the device illustrated in FIGS. 2a, 2b and 2c instead 
of the tubule 27 illustrated in those Figures. The rubber bands 42 assist 
in retaining the tubule 40 securely in the passageways 25, 26. When the 
device is disposed in an aqueous medium, a stationary liquid layer is 
retained between each of the rubber bands 42 and the tubule 40. 
Accordingly, the glass of the tubule 40 dissolves preferentially under the 
rubber bands 42 in a controlled manner. When the glass of the tubule 40 is 
perforated as a result of the dissolution, active material 41 can easily 
flow out of the tubule 40 via the perforation so formed. 
The present invention is based on the discovery by the present inventor 
that in situations where the diffusion of dissolution products away from 
the vicinity of a P.sub.2 O.sub.5 containing glass surface is constrained, 
the dissolution rate is related not only to the composition of the glass 
but also to the concentration of such products at the glass-solution 
interface, and the ability controllably to avoid the formation, on the 
surface of the glass, of a film which can interfere with dissolution. The 
formation of such a film particularly arises where the aqueous environment 
contains cations which can form insoluble phosphates e.g. Ca.sup.++ and 
Mg.sup.++. Such environments include hard water and body fluids of 
animals. Thus it is not only necessary to select a glass composition to 
get a particular dissolution rate, but also to select conditions for the 
dissolution of that glass in relation to its glass composition. Such a 
selection means that the presence of dissolution products in the aqueous 
medium in the vicinity of that glass surface does not interfere with the 
dissolution rate. Any such interference will render the selection of 
accurate time intervals for dissolution impossible. 
In the case of glasses with a P.sub.2 O.sub.5 content below about 40 mole % 
we have found that the total phosphate ions released when the glass 
dissolves contain only a small porportion of polyphosphate ions. 
Consequently, complexing of M.sup.++ ions in the aqueous medium by 
polyphosphate ions to produce soluble dissolution products may not take 
place at a sufficient rate to prevent the build up of the concentration of 
M.sup.++ ions adjacent the glass to a value at which film formation of 
insoluble phosphates occurs adjacent the glass surface. This inhibits 
dissolution of the glass and reduces the dissolution rate, generally by an 
unpredictable amount. 
For glasses having a P.sub.2 O.sub.5 content above about 50 mole %, the 
high proportion of polyphosphate ions in the total phosphate ions released 
when the glass dissolves tends to result in the formation of gelatinous 
complexed phosphate films adjacent the glass surface which also reduce the 
dissolution rate of the glass. 
In accordance with the present invention, in order to achieve a controlled 
dissolution rate the soluble phosphate glasses have a P.sub.2 O.sub.5 
content of from 40 to 50 mole %, preferably from 44 to 48 mole %. We have 
found that for glasses having a P.sub.2 O.sub.5 content of from 40 to 50 
mole %, the dissolution rate is substantially constant and controllable in 
any selected set of operating conditions, in particular over a selected 
concentration range of dissolution products in the stationary liquid 
layer. In the case of glasses with a P.sub.2 O.sub.5 content of from about 
44 to 48 mole %, we have found that the dissolution rate is independent of 
the concentration of the dissolution products over a wide range from about 
30ppm to 30000 ppm. The dissolution rate remains constant since the 
release of polyphosphate ions is such as to complex the M.sup.++ ions as 
fast as they arrive by diffusion from the bulk solution as well as the 
M.sup.++ ions released from the glass itself. As one moves towards 50 mole 
% P.sub.2 O.sub.5, the tendency for gelatinous films to form increases. As 
one moves below 45 mole % P.sub.2 O.sub.5, the tendency for dissolution 
products to separate, from a deposit and interfere with dissolution 
increases and the dissolution rate can only be controlled by a more 
careful control of the concentration of dissolution products. It is 
believed that this is due to the inability of the dissolution products, 
which in the case of the lower P.sub.2 O.sub.5 content glasses are 
primarily relatively short chain phosphate anions, to complex with ions 
such as Ca.sup.++ to form soluble complexes. This results in insoluble 
phosphate products forming a continuous or semicontinuous layer on the 
glass surface and reducing the dissolution rate at that surface. Moreover, 
the dissolution rate may decrease with time as the film becomes thicker so 
that it is not possible to achieve a time - independent solution rate. As 
the solution rate becomes more dependent on the concentration of the 
solution products it becomes necessary to maintain control of the 
concentration of the dissolution products at the glass/liquid interface 
within fairly narrow limits to achieve a predictable dissolution rate. 
Suitable glass compositions in the range 40 to 49 mole % P.sub.2 O.sub.5 
for use in the devices of the present invention disclosed above are shown 
in Table I below. It is preferred to minimize the use of Al.sub.2 O.sub.3 
as we have found that glasses containing more than 1.5 mole % Al.sub.2 
O.sub.3 do not give as consistent a performance as glasses in which the 
dissolution rate is varied using other materials such as CaO, MgO and ZnO. 
The glass compositions may contain components to tint the glass, different 
tints being chosen to indicate different dissolution rates. Any standard 
glass colouring oxide can be used. The concentration is normally less than 
0.5 mole %. Suitable oxides are e.g. nickel oxide or manganese oxide. 
TABLE I 
__________________________________________________________________________ 
All glass compositions in Mole % 
1 2 
3 4 
5 
6 
7 
8 
9 
10 
11 
12 13 
14 
15 16 17 
__________________________________________________________________________ 
P.sub.2 O.sub.5 
40 
45 
45 45 
45 
45 
45 
45 
45 
45 
45 
44.8 
47 
49 
45 45 45.0 
CaO 22 
20 
9 24 
18 
16 
14 
12 
10 
22 
14 
22.1 
20 
18 
6.0 
6.3 
6.15 
Na.sub.2 O 
38 
35 
39 31 
35 
35 
35 
35 
35 
33 
39 
33.1 
33 
33 
39.0 
39.0 
39.0 
MgO -- 
-- 
3 -- 
2 
4 
6 
8 
10 
-- 
2 
-- -- 
-- 
6.0 
6.5 
6.5 
ZnO -- 
-- 
3 -- 
-- 
-- 
-- 
-- 
-- 
-- 
-- 
-- -- 
-- 
3.0 
3.0 
3.0 
MnO -- 
-- 
1 -- 
-- 
-- 
-- 
-- 
-- 
-- 
-- 
-- -- 
-- 
1.0 
0 0 
Al.sub.2 O.sub.3 
-- 
-- 
-- -- 
-- 
-- 
-- 
-- 
-- 
-- 
-- 
-- -- 
-- 
0 0.2 
0.35 
__________________________________________________________________________ 
As indicated above, the dissolution rate is related to the concentration of 
dissolution products at the glass/solution interface. It is well known 
that when a solid surface is Present in a moving liquid there is always a 
thin, stationary film of this liquid held at the solid/liquid interface. 
The thickness of this thin film is an inverse function of how fast the 
bulk of the liquid is circulating and/or flowing past the solid surface at 
that point. The products of dissolution of the solid in the liquid are 
transported away from the solid surface to the bulk solution by diffusion 
through this film and any species in solution in the bulk solution are 
transported to the solid surface by diffusion through this film. It 
follows that the thinner this film, the lower will be the concentration of 
solution products at the solid-liquid interface. In a well-stirred liquid 
this stationary liquid film will be very thin, transport of dissolution 
products through it very fast and, consequently the concentration of 
dissolution Products at the solid-liquid interface is very low an the 
concentration at the solid-liquid interface of species present in the bulk 
solution is near to that of the bulk solution. In accordance with the 
present invention it is provided that the dissolution of the phosphate 
glass in the device of the invention occurs under such conditions that the 
thickness of the stationary liquid film is independent of the flow 
conditions in the bulk liquid. A uniform stationary liquid film thickness 
is maintained over the area where dissolution is occurring so that the 
rate at which the glass is dissolving, and the rate of diffusion of 
dissolution products out of the film, are at a value where the 
concentration of dissolution products in the film remains in the range 
where the dissolution rate for that particular glass remains substantially 
constant. In a steady state, the rate of diffusion of the products across 
the boundary between the surface film of the liquid and the bulk liquid 
will be equal to the rate at which the glass is dissolving. For any 
particular initial film thickness selected as described below, knowing the 
glass dissolution rate and the rate of removal of dissolution products by 
diffusion it is possible to calculate the concentration of dissolution 
products at the glass-liquid interface and also knowing the concentration 
of ion-species in the bulk solution it becomes possible to check whether 
the choice of a particular liquid film thickness results in a 
concentration in the desired range for a particular glass. 
In the three illustrated embodiments, the initial liquid film thickness is 
selected by control of the spacing between the end wall and the glass disc 
in the embodiment of FIG. 1; by the juxtaposition of the tubule and the 
passageway in the embodiment of FIG. 2; and by the placing of the rubber 
bands around the tubule in the embodiment of FIG. 3. The diffusion is 
controlled by providing a barrier which allows any escape from the 
constrained film to be by means of diffusion at a rate such that the 
concentration of the solution products in the film remains in the desired 
range. In other embodiments, the initial liquid film thickness may be 
selected by providing a thin water permeable barrier such as filter paper, 
a solid plate with holes, or a mesh to constrain the liquid film in place. 
In the embodiment of FIG. 3, preferential dissolution in a narrow band 
encircling the tubule in the region of the grommet at a faster rate than 
elsewhere can result in the tubule breaking apart at one or more places 
releasing its contents. The trapped film thickness will of course increase 
as the glass dissolves to that e.g. with a 2 mm thick soluble phosphate 
glass an initial choice of film thickness of 2.5 mm would increase to 4.5 
mm. We have found that any such change in film thickness does not produce 
an adverse change in the concentration of the solution products so as to 
interfere with the uniform dissolution of the glass surface exposed to the 
aqueous solution. 
The actual dimensions of a device are determined by the volume of active 
material such as e.g. an anthelmintic which it is desired to release from 
the device on dissolution of a glass retaining member e.g. in the form of 
a disc, or a wall of a capillary, and the elapsed time before that release 
takes place after immersion in the aqueous medium. The actual dissolution 
rate and the concentration of dissolution products needed to maintain 
substantially that actual dissolution rate can be set down for any 
situation. As broad criteria we have found with dissolution rates ranging 
from 0.05mg/cm.sup.2 /h to 5.0 mg/cm.sup.2 /h (i.e. ranging over 2 orders 
of magnitude), a glass with a composition in the range from 40 to 50 mole 
% P.sub.2 O.sub.5 will dissolve consistently if the concentration of 
solution products is maintained in the range 0.1 to 6 g/l. It is possible 
for the man skilled in the art designing a device which has a particular 
elapsed time before release of the active material at least to determine 
on a theoretical basis, an approximate film thickness for a particular 
glass having a known dissolution rate. Starting from that basis, the man 
can then determine experimentally the exact dimensions of the device 
needed to ensure a satisfactory layer thickness. For the dissolution 
process, in the steady state which is promoted by the existence of the 
stationary liquid layer, the rate of diffusion of dissolution products 
across the boundary between the stationary liquid layer and the bulk 
liquid is given by: 
##EQU1## 
where D is the diffusion constant, Cs is the concentration of solution 
products at the surface of the glass, x is the thickness of the stationary 
liquid layer and the concentration of solution products in the bulk liquid 
is assumed to be zero. In the steady state, R.sub.Boundary is equal to the 
rate R at which the glass is dissolving. From the equation it is possible 
to determine x, knowing R and C.sub.s, and C.sub.s knowing R and x. The 
devices of the invention when used e.g. to release anthelmintics could 
have production runs running in excess of several million, and hence the 
experimental work to define exact dimensions for a device so as to achieve 
Particular release characteristics is justifiable. Even such a device 
would probably go through several prototypes before the production version 
was approved. 
Experimental results illustrating the present invention will now be 
described. 
A number of the glass compositions specified in Table 1 were examined as 
described below in order to determine the various dissolution parameters 
and mechanisms. 
In order to demonstrate the effect of the concentration of the solution 
products in the liquid surrounding a phosphate glass, the solution rates 
of the above glasses were examined under different conditions. The 
solution rates were determined by measuring the loss of weight of a 
sample. Samples were simply removed at intervals from the solution and 
blotted dry with paper tissue. 
FIG. 4 is a graph showing the relationship between the dissolution rate 
R(mg cm.sup.-2 h.sup.-1) at 38.degree. C. and the molar Percent of P.sub.2 
O.sub.5 for a series of glass compositions. The dissolution rate was 
measured by suspending samples in an open neck nylon bag in liquid. The 
amount of P.sub.2 O.sub.5 varied between 30 and 55 mole %. The amount of 
CaO with compositions was a constant 23 mole % and the remainder of each 
composition comprised Na.sub.2 O. 
The graph shows the results for flowing distilled water and for static 
distilled water. The pH varied between notional limits of pH 5 to 8 due to 
the effects, inter alia, of dissolved atmospheric CO.sub.2 in the water, 
and ionic concentrations. 
In flowing distilled water, all glass compositions exhibit a controlled 
dissolution behaviour i.e. the value of R is reproducible and a unique 
function of the glass composition. This is because there are sufficient 
polyphosphate ions to complex the small amount of M.sup.++ ions present, 
namely those emanating from the glass, and a time - independent steady - 
state dissolution rate is established. 
In static distilled water, the value of R varies in a roughly similar 
manner to that in flowing distilled water but is reduced since there tends 
to be a higher concentration of M.sup.++ ions at the surface of the glass 
leading to the formation of phosphates which inhibit dissolution. 
Thus the dissolution behaviour of a phosphate glass can be influenced by 
choice of composition in relation to the environment in which it is to be 
used. 
Although not illustrated in a graph, we have found that in flowing hard tap 
water, the value of R is an order of magnitude or more lower than the 
value in flowing distilled water for glasses of the same composition. This 
value can change under certain conditions with elapsed time, and such 
changes can be abrupt. This is believed to be due to the presence of free 
M.sup.++ ions in the liquid layer adjacent to the glass surface which 
react with ortho- and pyro-phosphate ions released from the glass surface 
to form compounds with a low solubility product. The formation of these 
compounds can result in a continuous film being deposited on the glass, 
and the rate limiting process becomes the diffusion through this slightly 
permeable layer. Abrupt changes can then occur when there is an alteration 
of the integrity of the film. Film formation occurs, it is believed, when 
the water is sufficiently hard that there is a continuous supply of 
M.sup.++ ions to the glass in excess of the ability of the polyphosphates 
released from the glass to complex these ions to form soluble complexes. 
In a limited volume of hard water, the behaviour is dependent on the value 
of the dissolution rate R, and the most extreme type of behaviour is 
observed for glasses with values of the dissolution rate less than 0.1 
mg/cm/.sup.2 /h. The value of R falls as the insoluble phosphate film 
builds up, and continues at this reduced rate until sufficient 
polyphosphates are dissolved from the glass to complex all the M.sup.++ 
ions present in the solution. 
In the case of glasses with P.sub.2 O.sub.5 44 to 50 mole % and very low R, 
the surface film may persist for very long periods when the glass is 
exposed to hard water because of the low rate of release of polyphosphate 
complexing ions into the solution. Care should be therefore taken in 
choosing a glass for operating in hard water conditions to choose a 
composition with an R higher than about 0.1 in order to avoid such 
effects. This may mean using a device with a greater thickness of glass in 
order to achieve a particular elapsed time for the release of an active 
material. Alternatively polyphosphate ions may be provided from some other 
source such as a sacrificial supply of glass with a composition chosen to 
give an adequate release of polyphosphate ions rapidly to complex the 
Ca.sup.++ and Mg.sup.++ ions initially present in the stationary liquid 
layer. This can be done by e.g. combining solid rods or granules of glass 
as an integral part of any device. 
FIG. 5 is a graph showing the relationship between weight loss (in mg) and 
leaching time (in hours) for a series of five flat buttons made of a glass 
of composition in mole % P.sub.2 O.sub.5 40, CaO 22, Na.sub.2 O 38. The 
buttons of glass were cut 2 to 4 mm thick from a rod of about 1 cm 
diameter and were supported vertically in 40 ml unstirred solvent at 
38.degree. C. This was done by supporting the buttons between two pins on 
a rubber bung. The solvent is water, in four cases distilled water 
containing a selected initial concentration of the solution products of 
the glass under test and in one case being tap water (Hardness 340 ppm 
Ca.sup.++). 
The solution was static and the concentration of the dissolution products 
increased with time. 
The graph shows that with P.sub.2 O.sub.5 at 40 mole %, for relatively low 
initial concentrations of dissolution products (i.e. initial 
concentrations of 125, 320 and 3125 mgl.sup.-1), the dissolution rate R 
(which is related to the slope of the lines) is initially high but falls 
off as the concentration of solution products increases with time. Also, 
there is no concentration region in which R is independent of solution 
concentration. For a high initial concentration of dissolution products 
(i.e. initial concentration of 10000 mgl.sup.-1) and tap water, the 
dissolution rate R is too low for practical use, the rate being limited by 
the diffusion of water and dissolution products through the insoluble 
phosphate film which forms on the glass surface. 
Thus for phosphate glasses having 40 mole % P.sub.2 O.sub.5, the 
dissolution rate rate can vary greatly depending on the concentration of 
dissolution products in the aqueous solution. 
FIG. 6 is a graph showing the relationship between weight loss (in mg) and 
leaching time (in hours) at 38.degree. C. for a series of five buttons 
similar to those described above which were made glasses containing a 
constant amount of P.sub.2 O.sub.5 45 mole %, and a constant total of MO 
(where MO=CaO+MgO) at 18 mole %, and Na.sub.2 O 37 mole %. The glass were 
varied in composition from the MO content being solely CaO to CaO being 10 
mole % and MgO 8 mole %, by replacing CaO by MgO in 2 mole % steps. The 
buttons after etching were placed initially in 40 ml of tap water 
containing 1g/litre of solution products and this was maintained 
substantially constant for 100 hours, and the concentration was then 
increased to a substantially constant 2g/l for the remainder of the 
experiment. The solution was static. 
FIG. 6 shows that with a steady concentration of dissolution products, the 
value of R varies with the amount of MgO and CaO in the glass. The Figure 
also shows that R (related to the gradiant of each line) is substantially 
constant for each glass at each concentration of dissolution products 
examined. The small variation in the dissolution rates being the two 
different concentrations is due, inter alia, to changes in the pH of the 
solution which can vary with the concentration and also depends on the 
glass composition employed. Thus for a given phosphate glass composition 
having 45 mole % P.sub.2 O.sub.5, the dissolution rate R does not vary 
substantially as a result of changes in concentration of the dissolution 
products in the aqueous solution. 
FIGS. 7 and 8 are graphs showing the relationship between weight loss (in 
mg) and leaching time (in hours) for a further series of five buttons in 
different respective dissolution conditions. 
In the experiment of FIG. 7, a series of five buttons were made, the 
buttons being comprised of a glass containing a constant amount of P.sub.2 
O.sub.5 at 45 mole %, and an amount of CaO varying in steps of 2 mole % 
from 17 to 25 mole %, with a fall of Na.sub.2 O content from 38 mole % to 
30 mole %. The buttons were placed in 40 ml of distilled water containing 
10 g/l as a fixed initial amount of solution products, and the weight in 
mg was measured against time. The concentration of dissolution products 
was maintained substantially constant. The liquid was static. The results 
were plotted as weight loss against time for each glass, and the 
dissolution rate (R) calculated. 
In the experiment of FIG. 8, a further set of five buttons, the same as 
those used in the experiment whose results are given in FIG. 7, were 
examined under conditions in which the buttons were placed in 40 ml 
distilled water with no change in the aqueous solution being made during 
the course of measurements so that dissolution products built up in the 
solvent. The solvent was static. Weight loss in mg was then plotted 
against time and the dissolution rate (R) calculated for each glass. 
FIGS. 7 and 8 show that for a phosphate glass containing 45 mole % P.sub.2 
O.sub.5 the dissolution rate for any given glass under either of the 
conditions is substantially constant (i.e. the gradient of each line is 
substantially constant, apart from an initial start-up period before a 
steady state is reached). Those Figures also show that for any given glass 
composition containing 45 mole % P.sub.2 O.sub.5, the value of R is 
substantially the same whether the dissolution products remain at a 
constant concentration (FIG. 7) or are allowed to increase in 
concentration as dissolution continues (FIG. 8). Thus phosphate glasses 
having 45 mole % P.sub.2 O.sub.5 have dissolution rates which are 
relatively independent of the concentration of dissolution products in the 
aqueous solution. 
In FIGS. 7 and 8, the initial start-up period in which the gradient is not 
linear results from the initial state of the glass buttons. If the glass 
buttons are cut from a rod, the surface of the buttons will have 
irregularities on the cut surface. The influence of such irregularities on 
the dissolution rate was studied by preparing two samples of the same 
glass composition, one sample being as cut, and the other being etched 
before immersion in the solvent to reduce the thickness of the button by 
at least 0.2 mm as measured by a micrometer thereby to remove 
irregularities on the cut surface. Each sample button had the same glass 
composition in mole % of P.sub.2 O.sub.5 45, MgO 2, CaO 14 and Na.sub.2 O 
39. The buttons were immersed in 40 ml distilled water at 38.degree. C., 
with no change being made to the dissolved products composition during 
course of the measurements so that the dissolution products built up in 
the solvent. The results are shown in FIG. 9 which is a graph illustrating 
the relationship between weight loss (in mg) and leaching time (in hours). 
FIG. 9 simply demonstrates that when a glass is etched to remove the rough 
surface, the initial high rate of dissolution is not observed, and that 
the steady values of R are the same for each glass. This shows that for 
controlled dissolution it is important to be aware of this initial high 
rate if use of glasses with damaged surfaces cannot be avoided. This is 
consistent with FIGS. 7 and 8 wherein the initial high dissolution rates 
represented by the curved portions of the plots were due to the presence 
of cut surfaces on the buttons. 
FIGS. 10a to 10g are graphs showing the relationship between the 
dissolution rate R (in mg cm.sup.-2 h.sup.-1) at 38.degree. C. and the 
logarithm of the concentration of the solution products (in mg 1.sup.-1) 
for a variety of soluble phosphate glass compositions. FIG. 10a 
demonstrates that with P.sub.2 O.sub.5 at 40 mole %, as the concentration 
of dissolution products increases with time, there is a falling off in the 
value of R, and there is no concentration region in which R is independent 
of solution concentration. This is consistent with the three upper lines 
in FIG. 4. Hence if one wishes to achieve a reasonably constant 
dissolution rate with a 40 mole % P.sub.2 O.sub.5 glass it is essential in 
this case to avoid the concentration of dissolution products building up 
in the region of the glass surface, and to keep that concentration at a 
leval where the desired dissolution rate can be achieved. It is clearly 
preferable if possible to avoid working in this glass-composition region 
unless accurate control of the concentration of dissolution products can 
be achieved and the glass chosen has the desired dissolution rate under 
those conditions. One situation where it would be possible to work with 
glasses of about 40 mole % P.sub.2 O.sub.5 is where the water was 
naturally soft or was artificially softened so as to be substantially free 
of calcium and magnesium ions. 
As the glass composition varies from 40 to about 44 mole % P.sub.2 O.sub.5, 
this requirement to have a carefully controlled specific concentration of 
dissolution products is reduced and it is possible to get a substantially 
controlled dissolution rate over a narrow concentration range. 
As the glass composition reaches 44 mole % P.sub.2 O.sub.5 and above, there 
is a fairly broad concentration range which still provides a substantially 
constant dissolution rate. 
FIGS. 10b to 10g demonstrate that for glasses of differing compositions 
between 44.8 and 49 mole % P.sub.2 O.sub.5, the dissolution rate R is 
substantially constant with varying concentration of dissolution products 
in the solvent over a particular concentration range. This is represented 
by the flat portion of the plot. It should be noted that the actual value 
of R varies greatly between different glass compositions. 
FIG. 11 is a graph showing the relationship between the mole % P.sub.2 
O.sub.5 in the glass compositions of FIGS. 10a to 10g and the logarithm of 
the concentration --the graph having been compiled from the data of FIGS. 
10a to 10g. It may be seen that for each glass composition there is a 
concentration range in which R is independent (+5%) of concentration, each 
range being respectively represented by a horizontal straight line. The 
horizontal straight lines together define an approximate area, which is 
shown hatched, which defines a region wherein for any given P.sub.2 
O.sub.5 molar amount the value of R does not substantially vary over the 
relevant concentration range. Thus, when designing controlled delivery 
devices in accordance with the present invention, if one selects a 
particular molar percentage of P.sub.2 O.sub.5 for the glass composition 
it is possible to determine within which concentration range the device 
must be employed in order to obtain a substantially constant dissolution 
rate. It will be seen from FIG. 11 that as the value of P.sub.2 O.sub.5 
approaches 50 mole %, the region where R is constant becomes limited in 
size and as P.sub.2 O.sub.5 approaches 40 mole % the region becomes 
vanishingly small.