WO1990011756A1 - Slow release vitreous systems - Google Patents

Slow release vitreous systems Download PDF

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Publication number
WO1990011756A1
WO1990011756A1 PCT/GB1990/000497 GB9000497W WO9011756A1 WO 1990011756 A1 WO1990011756 A1 WO 1990011756A1 GB 9000497 W GB9000497 W GB 9000497W WO 9011756 A1 WO9011756 A1 WO 9011756A1
Authority
WO
WIPO (PCT)
Prior art keywords
glass
active agent
release
water soluble
vitreous
Prior art date
Application number
PCT/GB1990/000497
Other languages
French (fr)
Inventor
James Lewis Wardell
John Alaister Duffy
Original Assignee
Aberdeen University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GB898908273A external-priority patent/GB8908273D0/en
Priority claimed from GB898909843A external-priority patent/GB8909843D0/en
Application filed by Aberdeen University filed Critical Aberdeen University
Publication of WO1990011756A1 publication Critical patent/WO1990011756A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2009—Inorganic compounds
    • C—CHEMISTRY; METALLURGY
    • C03—GLASS; MINERAL OR SLAG WOOL
    • C03C—CHEMICAL COMPOSITION OF GLASSES, GLAZES OR VITREOUS ENAMELS; SURFACE TREATMENT OF GLASS; SURFACE TREATMENT OF FIBRES OR FILAMENTS MADE FROM GLASS, MINERALS OR SLAGS; JOINING GLASS TO GLASS OR OTHER MATERIALS
    • C03C3/00—Glass compositions
    • C03C3/12—Silica-free oxide glass compositions
    • C—CHEMISTRY; METALLURGY
    • C03—GLASS; MINERAL OR SLAG WOOL
    • C03C—CHEMICAL COMPOSITION OF GLASSES, GLAZES OR VITREOUS ENAMELS; SURFACE TREATMENT OF GLASS; SURFACE TREATMENT OF FIBRES OR FILAMENTS MADE FROM GLASS, MINERALS OR SLAGS; JOINING GLASS TO GLASS OR OTHER MATERIALS
    • C03C4/00—Compositions for glass with special properties
    • C03C4/0035—Compositions for glass with special properties for soluble glass for controlled release of a compound incorporated in said glass

Definitions

  • the present invention relates to slow-release vitreous systems particularly for the release of biologically active materials to an aqueous environment of use over a predetermined time period.
  • Slow-release systems are well known in the art but tend to be specialised becaused of their inherent expense.
  • Slow-release systems are for example used in the pharmaceutical industry for the administration of biologically active agents to a patient over a predetermined time span at a constant or varying rate depending upon the circumstances.
  • Other slow-release systems are known for other purposes, but all suffer from the inherent expense or lack of flexibility of the slow-release vehicle.
  • Glass is a relatively cheap material, and the glasses which are water soluble are known. Indeed phosphate glasses have been used to release inorganic substances which are thermostable since the softening point of
  • phosphate glasses is for example 400 - 500°C. These phosphate glasses have a widely varying dissolution rate depending upon the precise constitution of the watersoluble glass chosen and are hence able to transmit inorganic salts to an environment of use over a predetermined time period.
  • Low melting point water soluble glasses for example the acetate glasses have been described in The Journal of the American Ceramic Society Vol 52, No. 4 April 1969 Pages 224-225. Further nitrate glasses have been described, as such, in the Journal of The Chemical Society 1969 pages 2398 et seq. It has not however been appreciated that the combination of the low softening point of the acetate and other carboxylates and nitrate type glasses combined with their variable water solubility provides an excellent slow release vehicle for heat-sensitive substances, such as biologically active substances, to an aqueous environment of use.
  • GB-A-2,182,034 discloses a vitreous system in which organic materials are incorporated in a water soluble glass by forming a sintered porous body and filling the same with an organic material in liquid form. This disclosure teaches against incorporating organic materials directly into the glass.
  • a slow release vitreous system comprising a water soluble glass having a softening point of less
  • glass describes amorphous material derived for example from carboxylates and nitrates.
  • the active agents which can be biologically active or nonbiologically active, need be stable only to the temperature of the softening point of the glass (see Table 1) . This illustrates the advantages of these glasses: compounds with low decomposition temperatures can be safely entrapped or dissolved with little decomposition.
  • the water soluble glass is a carboxylate, nitrate, sulphate or bisulphate glass having a low softening point, e.g.
  • the glass may be selected from a compound of the formula
  • R 1 and R2 are the same or different and are selected from
  • x has a value of 1 - 3;
  • R 1 and M2 are the same or different and are selected from H, an alkali metal or an alkaline earth metals or a chemically appropriate metal such as lead or zinc.
  • R 1 and M2 are the same or different and are selected from H, an alkali metal or an alkaline earth metals or a chemically appropriate metal such as lead or zinc.
  • M 1 and M2 are lithium, sodium, potassium, calcium, lead or zinc.
  • the glass selected is made from either a single salt or a mixture of salts or a mixture of salts and acids having general formula
  • M 1 , M2, M3... are the same or different and are selected from H, alkali metals or alkaline earth metals or a chemically appropriate metal such as zinc
  • a 1, A , A3 ... are the same or different and are selected from carboxylates preferably chiral carboxylates, such as tartrates nitrate, sulphate or bisulphate; wherein a, b, c ...
  • the invention is further characterised by a method for the production of a slow-release system which method comprises;
  • the glass dissolves to release the active agent over a predetermined time period.
  • the glasses as just described may be coated with a coating material to further modify the slow-release rate of the active agent to the environment of use.
  • the shape and geometry of the water soluble glass may also be adjusted to alter the release rates.
  • the coating material as just described may be a phosphate glass or any selected polymeric material so chosen as to give a desired rate of agent release (see Table 2 below) .
  • the geometry of the system in accordance with the present invention is important. It will be appreciated that the larger the system particle, the smaller the total surface area and hence the slower the release rate in aqueous environment of use. Thus physically relatively large slow-release systems in accordance with the present invention will release the active agent to the environment of use slower than small particles. Thus the constant release rate to an environment of use can be achieved over a long time period by not only selecting the materials from which the release systems are made, but also by altering the relative particle sizes in a mixture applied to an environment of use.
  • the geometry of the slow-release system in accordance " with the present invention may be configured to adjust the output rate of the active agent to an environment of use by altering the rate at which readily soluble glass is exposed for dissolution.
  • the geometry of the slow-release system in accordance " with the present invention may be configured to adjust the output rate of the active agent to an environment of use by altering the rate at which readily soluble glass is exposed for dissolution.
  • a multi-layer system may be achieved by providing a central core of the water soluble glass in accordance with the present invention, overlaid by, for example, a coating of a phosphate glass.
  • the relative diameter of the central core which need not be uniform throughout its length, can be adjusted to provide a desired predetermined dissolution rate.
  • the active agents in accordance with the present invention may for example be pharmaceutically active agents such as hormones and amino-acids, for administration to agriculturally significant animals for example to ruminants.
  • the active agents may be any suitable pharmaceutical agent such as an antibiotic which can be administered to a patient for slow-release.
  • slow-release systems of the present invention can be provided with pheromones which can be utilized to attract specific insects to a specific site.
  • the pheromones can be specific to an insect which is a pest on a particular crop. Tomatoes for example can be cleared of insect pests in a closed tomato growing area without application of toxic materials to the plants themselves. Since pheromones are specific to insects of a particular sex as well as a particular type, it is also possible to separate males and females of a particular species by this method.
  • fertilizers are formed with nitrogen, phosphorus, and potassium for administration to a crop in a seed bed preferably in a single pass operation.
  • the slow-release systems in accordance with the present invention of this type may also include insecticides, fungicides, or other pesticides in general which act to protect the crop during its growing season, (about three or four months), without the necessity for regular spraying.
  • slow-release systems in accordance of this type will be incoporated into the seed bed at the same time as the seed are sown thereby providing long term protection from pest attack as well as fertilization throughout its growing period.
  • the invention is also suitable for the slow-release of descaling agents for pipes and boilers and for the slow-release of bactericidal agents to water storage systems for the prevention, for example, of Leqionella .
  • the systems in accordance with the present invention may also be utilized as wood preservatives for in situ applications.
  • Carboxylate glasses were formed by standard methods to have the following consitution as shown in Table 1.
  • a dissolution rate could be adjusted to be between 24 minutes and 70 days. Since the dissolution rate of the acetate glasses is faster than that of the phosphate glasses in general it will be noted that the slow-release system can be adjusted to release its bolus within any desired time frame. Further by altering the relative geometry of the coating and the core it is possible to release more or less active agent to the enviroment of use over a predetermined portion of the time frame.
  • the invention therefore comprehends not only a slow-release system and a method for the production thereof, but a method of administering an active agent to an environment of use, said enviroment of use being agricultural, veterinary, human or industrial.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Geochemistry & Mineralogy (AREA)
  • Materials Engineering (AREA)
  • Organic Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention provides a slow release vitreous system comprising a water soluble glass having a softening point of less than 320°C and preferably less than 200°C wherein said water soluble glass has dissolved or admixed therein an active agent such as a pharmaceutical which is stable at the melting point of the glass and which releases to an aqueous environment of use over a predetermined time period.

Description

SLOW RELEASE VITREOUS SYSTEMS
The present invention relates to slow-release vitreous systems particularly for the release of biologically active materials to an aqueous environment of use over a predetermined time period.
Slow-release systems are well known in the art but tend to be specialised becaused of their inherent expense. Slow-release systems are for example used in the pharmaceutical industry for the administration of biologically active agents to a patient over a predetermined time span at a constant or varying rate depending upon the circumstances. Other slow-release systems are known for other purposes, but all suffer from the inherent expense or lack of flexibility of the slow-release vehicle.
Glass is a relatively cheap material, and the glasses which are water soluble are known. Indeed phosphate glasses have been used to release inorganic substances which are thermostable since the softening point of
phosphate glasses is for example 400 - 500°C. These phosphate glasses have a widely varying dissolution rate depending upon the precise constitution of the watersoluble glass chosen and are hence able to transmit inorganic salts to an environment of use over a predetermined time period.
Low melting point water soluble glasses for example the acetate glasses have been described in The Journal of the American Ceramic Society Vol 52, No. 4 April 1969 Pages 224-225. Further nitrate glasses have been described, as such, in the Journal of The Chemical Society 1969 pages 2398 et seq. It has not however been appreciated that the combination of the low softening point of the acetate and other carboxylates and nitrate type glasses combined with their variable water solubility provides an excellent slow release vehicle for heat-sensitive substances, such as biologically active substances, to an aqueous environment of use.
GB-A-2,182,034 discloses a vitreous system in which organic materials are incorporated in a water soluble glass by forming a sintered porous body and filling the same with an organic material in liquid form. This disclosure teaches against incorporating organic materials directly into the glass.
According therefore to the present invention there is provided a slow release vitreous system comprising a water soluble glass having a softening point of less
than 320 C characterised in that said water soluble glass has dissolved, or admixed therein, an active agent which releases to an aqueous environment of use over a predetermined time period.
Where "glass" describes amorphous material derived for example from carboxylates and nitrates. The active agents, which can be biologically active or nonbiologically active, need be stable only to the temperature of the softening point of the glass (see Table 1) . This illustrates the advantages of these glasses: compounds with low decomposition temperatures can be safely entrapped or dissolved with little decomposition.
In a preferred form of the invention the water soluble glass is a carboxylate, nitrate, sulphate or bisulphate glass having a low softening point, e.g.
below 200°C.
The glass may be selected from a compound of the formula
2 2
R^ K1.
wherein R 1 and R2 are the same or different and are selected from
(alkyl -COO-
wherein x has a value of 1 - 3;
and wherein 1 and M2 are the same or different and are selected from H, an alkali metal or an alkaline earth metals or a chemically appropriate metal such as lead or zinc. In a preferred embodiment of the foregoing formula; R
2 and R may be CH3 C00-; the preferred substituent for
M 1 and M2 are lithium, sodium, potassium, calcium, lead or zinc.
In a further aspect of the invention the glass selected is made from either a single salt or a mixture of salts or a mixture of salts and acids having general formula
m1(M1A1 a):m2(M2A2 b): 3(M3A^ ):
wherein M 1 , M2, M3... are the same or different and are selected from H, alkali metals or alkaline earth metals or a chemically appropriate metal such as zinc
or lead wherein A 1, A , A3 ... are the same or different and are selected from carboxylates preferably chiral carboxylates, such as tartrates nitrate, sulphate or bisulphate; wherein a, b, c ...
depend on the valencies of M1, M2, M3... and A1, A2,
3 A ...; wherein m., π , n ... are the same or different .
The invention is further characterised by a method for the production of a slow-release system which method comprises;
selecting a water soluble glass having an appropriate
softening point below 320°C and preferably below 200°C; carefully heating said selected glass to its softening temperature,
causing said softened glass to come into intimate contact with an active agent thereby to cause the active agent to be dissolved by, or be admixed therein,
subsequently cooling said system; whereby on exposure of the cooled system to an aqueous environment of use, the glass dissolves to release the active agent over a predetermined time period. The glasses as just described may be coated with a coating material to further modify the slow-release rate of the active agent to the environment of use. The shape and geometry of the water soluble glass may also be adjusted to alter the release rates.
The coating material as just described may be a phosphate glass or any selected polymeric material so chosen as to give a desired rate of agent release (see Table 2 below) .
The geometry of the system in accordance with the present invention is important. It will be appreciated that the larger the system particle, the smaller the total surface area and hence the slower the release rate in aqueous environment of use. Thus physically relatively large slow-release systems in accordance with the present invention will release the active agent to the environment of use slower than small particles. Thus the constant release rate to an environment of use can be achieved over a long time period by not only selecting the materials from which the release systems are made, but also by altering the relative particle sizes in a mixture applied to an environment of use.
Further the geometry of the slow-release system in accordance " with the present invention may be configured to adjust the output rate of the active agent to an environment of use by altering the rate at which readily soluble glass is exposed for dissolution. Thus for example it is possible to form a multi-layer system wherein layers of the water soluble glass in accordance with the present invention are overlaid by a phosphate glass or other polymeric material. It will be appreciated that the relative thicknesses of the layers can be adjusted to achieve a desired dissolution rate.
Alternatively a multi-layer system may be achieved by providing a central core of the water soluble glass in accordance with the present invention, overlaid by, for example, a coating of a phosphate glass. The relative diameter of the central core which need not be uniform throughout its length, can be adjusted to provide a desired predetermined dissolution rate. The active agents in accordance with the present invention may for example be pharmaceutically active agents such as hormones and amino-acids, for administration to agriculturally significant animals for example to ruminants. Alternatively the active agents may be any suitable pharmaceutical agent such as an antibiotic which can be administered to a patient for slow-release.
Alternatively slow-release systems of the present invention can be provided with pheromones which can be utilized to attract specific insects to a specific site. By way of example the pheromones can be specific to an insect which is a pest on a particular crop. Tomatoes for example can be cleared of insect pests in a closed tomato growing area without application of toxic materials to the plants themselves. Since pheromones are specific to insects of a particular sex as well as a particular type, it is also possible to separate males and females of a particular species by this method. In a further aspect of the invention for which a nitrate glass may be used, fertilizers are formed with nitrogen, phosphorus, and potassium for administration to a crop in a seed bed preferably in a single pass operation. Further the slow-release systems in accordance with the present invention of this type may also include insecticides, fungicides, or other pesticides in general which act to protect the crop during its growing season, (about three or four months), without the necessity for regular spraying.
It is envisaged that slow-release systems in accordance of this type will be incoporated into the seed bed at the same time as the seed are sown thereby providing long term protection from pest attack as well as fertilization throughout its growing period.
The invention is also suitable for the slow-release of descaling agents for pipes and boilers and for the slow-release of bactericidal agents to water storage systems for the prevention, for example, of Leqionella . The systems in accordance with the present invention may also be utilized as wood preservatives for in situ applications.
The invention will now be described, by way of illustration only in the following examples of the inventio .
Example 1
Carboxylate glasses were formed by standard methods to have the following consitution as shown in Table 1.
Table 1
Carboxylate Glasses
Glass Mole Ratio
Figure imgf000014_0001
°C
CH3C02Li:CH3CO2Na 1.33:1 160
CH3C02 :(CH3Cθ2)2Ca 1:1 270
CH3C02Na:(CH3CO2)2Ca 1:1 310
2:1 —
CH3C02 :(CH3C02)2Ca 2:1 -
CH3C02Li:(CH3C02)2Pb 1:1 -
(CH3C02)2Pb:CH3C02K 3:1 -
CH3C02Na:(CH3CO2) 2 Zn 1:1 180
CH3C02K:(C2H5C02)2Ca:C4HgC02Na 1:1:1 150
CH3C02 :(CH3C02)2Ca:CyH^COj a 2:2:1 150
(CH3C02)2Ca:C15H31C02Na 3:4 150 Glasses of this type were softened to their softening temperatures and active lactones and esters were incorporated thereinto. These were subsequently recovered from the carboxylate glasses so formed by dissolving the same in an aqueous solution and extracting the target substance from the solution so formed. It was found that the lactones and esters were substantially recoverable.
Selected carboxylate glasses of Table 1 in the form of a rod were then coated with a phosphate glass in accordance with Table 2.
Table 2
Examples of Phosphate coatinqs
Glass Ratio Softening Dis¬ Composition Temperature C solution Rate*
Na20:P205 1:1 440 24 mins
Na20:CaO:P205 2:2:3 - 8 hrs 20 mins 20:CaO:P205 2:2:3 560 5 days
K20:CaO:P205 4:2:5 480 1 hr
10 mins
K20:Na20:P205 1:2:2 - 14 mins
Li20:ZnO:P205 1:3:6 <400 31 days
Li20:ZnO:P205 2:1:7 4.! 9 days
Li20:ZnO:MgO.P205 2:1:0.2:6.8 <400 25 hrs
Li20:ZnO:BaO:Na : 1.95:0.65:0.65: P2°5 0.25:6.5 370
Na20:CaO:MgO:P205 4.4:0.6:0.5:4.5 320 No significant loss in weight after 20 hours a20:ZnO:P205 2:1.5:6.5 370 69 days
Li20:ZnO:Na20:P205 1:1.5:1.5:6 380 No significant loss in weight after 20 hrs
MgO:ZnO:P205 0.5:0.5:9
K20:MgO:ZnOΪP2°5
* Rate at which a tablet of glass (1 g, 450-550 mm ) dissolves to 50% of its original mass in 200 mis of water. The rod was exposed to the atmosphere at each end of the structure so formed. By selection of the phosphate glasses as shown, a dissolution rate could be adjusted to be between 24 minutes and 70 days. Since the dissolution rate of the acetate glasses is faster than that of the phosphate glasses in general it will be noted that the slow-release system can be adjusted to release its bolus within any desired time frame. Further by altering the relative geometry of the coating and the core it is possible to release more or less active agent to the enviroment of use over a predetermined portion of the time frame.
The invention therefore comprehends not only a slow-release system and a method for the production thereof, but a method of administering an active agent to an environment of use, said enviroment of use being agricultural, veterinary, human or industrial.

Claims

1. A slow release vitreous system comprising a water soluble glass having a softening point of less than
320°C; characterised in that said water soluble glass has dissolved or admixed therein an active agent which is stable' at the melting point of the glass and which releases to an aqueous environment of use over a predetermined time period.
2. A system according to claim 1 characterised in that the glass is a carboxylate, nitrate, sulphate or bisulpate glass having a softening point below
200°C.
3. A system according to either of claims 1 or 2 characterised in that the glass is selected from a compound of the formula
R 1- U1~i R2- T2 wherein R1 and R2 are the same or different and are selected from (alkyl -COO-) <_& wherein x has a value of
1 - 3,
and wherein M1 and M2 are the same or different and are selected from H, an alkali metal or an alkaline earth metal or a chemically appropriate metal.
4. A system according to claim 3 characterised in that the chemically appropriate metal is lead or zinc.
5. A system according to either of claims 1 or 2 characterised in that the glass is selected from a single salt or mixture of salts with or without acids of the general formula:
m1(M1A1 a):m2(M2A2 b):m3(M3A3 ):
wherein M 1 , M2, M3... are the same or different and axe selected from H, alkali metals or alkaline earth metals or a chemically appropriate metal wherein A1, A2 , A3 ... are the same or different and are selected from carboxylates nitrates, sulphates or bisulphates and
wherein a, b, c ... depend upon the valencies of M and A and wherein mιr π , π ... are the same or
different.
6. A system according to any preceding claim characterised in the vitreous glass as defined is coated with a phosphate glass having a predetermined solution rate.
7. A system according to any preceding claim characterised in that the geometry of the vitreous system is configured to adjust the output rate of the active agent to the aqueous environment of use by adjusting the rate at which readily soluble glass is exposed for dissolution.
8. A system according to claim 7 characterised in that the system is a multilayer system comprising layers of water soluble glass according to any of claims 1 to 5 overlaid by a phosphate glass of claim 6 or other polymeric material; thereby to adjust rates of dissolution to a desired pattern.
9. A system according to claim 7 characterised in that the system is formed of a central core coated with a phosphate class of claim 6.
10. A system according to any preceding claim characterised in that the active agent is selected from a hormone, an amino acid, an antibiotic, a bacteriocide or an agricultural chemical.
11. A method for the controlled release an agricultural, horticultural, or pharmaceutical active agent to an environment of use which comprises delivering such an agent to said environment when dissolved or intimatedly admixed in a vitreous system according to any of claims 1 to 10.
12. A method for the production of a slow-release vitreous system which method comprises:- selecting a water soluble glass having an appropriate
softening point below 320 C, carefully heating said selected glass to its softening temperature.
causing said softened glass to come into intimate contact with an active agent thereby to cause the active agent to be dissolved by, or be admixed therein,
subsequently cooling said system; whereby on exposure of the cooled system to an aqueous environment of use, the glass dissolves to release the active agent over a predetermined time period.
PCT/GB1990/000497 1989-04-12 1990-04-03 Slow release vitreous systems WO1990011756A1 (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB898908273A GB8908273D0 (en) 1989-04-12 1989-04-12 Slow release vitreous systems
GB8908273.9 1989-04-12
GB898909843A GB8909843D0 (en) 1989-04-28 1989-04-28 Slow release vitreous systems
GB8909843.8 1989-04-28

Publications (1)

Publication Number Publication Date
WO1990011756A1 true WO1990011756A1 (en) 1990-10-18

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WO1996003978A1 (en) * 1994-08-04 1996-02-15 Quadrant Holdings Cambridge Limited Solid delivery systems for controlled release of molecules incorporated therein and methods of making same
US5998315A (en) * 1994-08-02 1999-12-07 Morgan Crucible Company Plc Strontium aluminate inorganic fibers
US6102896A (en) * 1999-09-08 2000-08-15 Cambridge Biostability Limited Disposable injector device
US6290991B1 (en) 1994-12-02 2001-09-18 Quandrant Holdings Cambridge Limited Solid dose delivery vehicle and methods of making same
US6352722B1 (en) 1997-12-23 2002-03-05 Quadrant Holdings Cambridge Limited Derivatized carbohydrates, compositions comprised thereof and methods of use thereof
US6468782B1 (en) 1996-12-05 2002-10-22 Quadrant Healthcare (Uk) Limited Methods of preserving prokaryotic cells and compositions obtained thereby
US6517860B1 (en) 1996-12-31 2003-02-11 Quadrant Holdings Cambridge, Ltd. Methods and compositions for improved bioavailability of bioactive agents for mucosal delivery
US6586006B2 (en) 1994-08-04 2003-07-01 Elan Drug Delivery Limited Solid delivery systems for controlled release of molecules incorporated therein and methods of making same
US6623762B2 (en) 2001-02-16 2003-09-23 Cambridge Biostability Ltd. Composition and method for controlled release injections
US6632648B1 (en) 1996-05-14 2003-10-14 Elan Drug Delivery Limited Methods of terminal sterilization of fibrinogen
US6964771B1 (en) 1995-06-07 2005-11-15 Elan Drug Delivery Limited Method for stably incorporating substances within dry, foamed glass matrices
WO2011048379A2 (en) 2009-10-21 2011-04-28 Innovata Limited Composition
WO2012159632A1 (en) * 2011-05-26 2012-11-29 Vestergaard Frandsen Sa Sintered glass for release of nutrients or other agents
US8486439B2 (en) 2007-03-01 2013-07-16 Bioneedle Technologies Group B.V. Parenteral formulation
US8877162B2 (en) 2000-05-10 2014-11-04 Novartis Ag Stable metal ion-lipid powdered pharmaceutical compositions for drug delivery
US8883830B2 (en) 2003-06-20 2014-11-11 Afgin Pharma LLC. Topical therapy for the treatment of migraines, muscle sprains, muscle spasms, spasticity and related conditions
US9421166B2 (en) 2001-12-19 2016-08-23 Novartis Ag Pulmonary delivery of aminoglycoside
US9554993B2 (en) 1997-09-29 2017-01-31 Novartis Ag Pulmonary delivery particles comprising an active agent
WO2022237992A1 (en) * 2021-05-14 2022-11-17 Bimeda Animal Health Limited A water-soluble glass rumen bolus
WO2022237993A1 (en) * 2021-05-14 2022-11-17 Bimeda Animal Health Limited A water soluble or water dispersible bolus article containing bromoform

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US3649551A (en) * 1970-09-08 1972-03-14 Corning Glass Works Glassy acetate material
EP0009338A1 (en) * 1978-09-26 1980-04-02 International Standard Electric Corporation Glass composition
FR2521835A1 (en) * 1982-02-23 1983-08-26 Univ Leeds Ind Service Ltd WATER-SOLUBLE GLASS ARTICLES, THEIR MANUFACTURE AND THEIR USE FOR THE TREATMENT OF RUMINANTS
SU1351978A1 (en) * 1986-02-12 1987-11-15 Уральский политехнический институт им.С.М.Кирова Fusible glass

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US3649551A (en) * 1970-09-08 1972-03-14 Corning Glass Works Glassy acetate material
EP0009338A1 (en) * 1978-09-26 1980-04-02 International Standard Electric Corporation Glass composition
FR2521835A1 (en) * 1982-02-23 1983-08-26 Univ Leeds Ind Service Ltd WATER-SOLUBLE GLASS ARTICLES, THEIR MANUFACTURE AND THEIR USE FOR THE TREATMENT OF RUMINANTS
SU1351978A1 (en) * 1986-02-12 1987-11-15 Уральский политехнический институт им.С.М.Кирова Fusible glass

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CHEMICAL ABSTRACTS, Vol. 108, 1988 (Columbus, Ohio, US) see page 322* Abstract No. 61225x, & SU, A, 1351978 (Ural Polytechnic Institute) 15 November 1987* *
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