GB2087721A - Injectable antibiotic formulations stabilised with glycofurol - Google Patents
Injectable antibiotic formulations stabilised with glycofurol Download PDFInfo
- Publication number
- GB2087721A GB2087721A GB8133767A GB8133767A GB2087721A GB 2087721 A GB2087721 A GB 2087721A GB 8133767 A GB8133767 A GB 8133767A GB 8133767 A GB8133767 A GB 8133767A GB 2087721 A GB2087721 A GB 2087721A
- Authority
- GB
- United Kingdom
- Prior art keywords
- glycofurol
- water
- pharmaceutical composition
- soluble salt
- water soluble
- Prior art date
- Legal status (The legal status 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 status listed.)
- Granted
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 20
- CTPDSKVQLSDPLC-UHFFFAOYSA-N 2-(oxolan-2-ylmethoxy)ethanol Chemical compound OCCOCC1CCCO1 CTPDSKVQLSDPLC-UHFFFAOYSA-N 0.000 title claims abstract description 19
- 238000009472 formulation Methods 0.000 title abstract description 5
- 230000003115 biocidal effect Effects 0.000 title 1
- 229930186147 Cephalosporin Natural products 0.000 claims abstract description 18
- 229940124587 cephalosporin Drugs 0.000 claims abstract description 18
- 150000003839 salts Chemical class 0.000 claims abstract description 18
- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 claims abstract description 16
- 150000001780 cephalosporins Chemical class 0.000 claims abstract description 15
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 claims abstract description 13
- 229960003324 clavulanic acid Drugs 0.000 claims abstract description 13
- 230000003444 anaesthetic effect Effects 0.000 claims abstract description 3
- 238000010348 incorporation Methods 0.000 claims abstract 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 23
- 229930182555 Penicillin Natural products 0.000 claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 229940049954 penicillin Drugs 0.000 claims description 12
- 229960003022 amoxicillin Drugs 0.000 claims description 11
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 claims description 11
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 9
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 8
- 229910052708 sodium Inorganic materials 0.000 claims description 8
- 239000011734 sodium Substances 0.000 claims description 8
- 239000004480 active ingredient Substances 0.000 claims description 7
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 claims description 6
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 3
- 229940102223 injectable solution Drugs 0.000 claims description 3
- 229910052700 potassium Inorganic materials 0.000 claims description 3
- 239000011591 potassium Substances 0.000 claims description 3
- ABVRVIZBZKUTMK-JSYANWSFSA-M potassium clavulanate Chemical compound [K+].[O-]C(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 ABVRVIZBZKUTMK-JSYANWSFSA-M 0.000 claims description 3
- 229960000723 ampicillin Drugs 0.000 claims description 2
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 claims description 2
- 239000003242 anti bacterial agent Substances 0.000 claims description 2
- 229950004030 cefaloglycin Drugs 0.000 claims description 2
- FUBBGQLTSCSAON-PBFPGSCMSA-N cefaloglycin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)COC(=O)C)C(O)=O)=CC=CC=C1 FUBBGQLTSCSAON-PBFPGSCMSA-N 0.000 claims description 2
- 229960002588 cefradine Drugs 0.000 claims description 2
- 229940106164 cephalexin Drugs 0.000 claims description 2
- ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 claims description 2
- RDLPVSKMFDYCOR-UEKVPHQBSA-N cephradine Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CCC=CC1 RDLPVSKMFDYCOR-UEKVPHQBSA-N 0.000 claims description 2
- RPBAFSBGYDKNRG-NJBDSQKTSA-N epicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CCC=CC1 RPBAFSBGYDKNRG-NJBDSQKTSA-N 0.000 claims description 2
- 229960002457 epicillin Drugs 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- YECIFGHRMFEPJK-UHFFFAOYSA-N lidocaine hydrochloride monohydrate Chemical compound O.[Cl-].CC[NH+](CC)CC(=O)NC1=C(C)C=CC=C1C YECIFGHRMFEPJK-UHFFFAOYSA-N 0.000 abstract description 3
- 239000007972 injectable composition Substances 0.000 abstract description 2
- 150000002960 penicillins Chemical class 0.000 description 5
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- -1 cephalosporin salt Chemical class 0.000 description 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 2
- KYARBIJYVGJZLB-UHFFFAOYSA-N 7-amino-4-hydroxy-2-naphthalenesulfonic acid Chemical compound OC1=CC(S(O)(=O)=O)=CC2=CC(N)=CC=C21 KYARBIJYVGJZLB-UHFFFAOYSA-N 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical group OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000838698 Togo Species 0.000 description 1
- 239000001089 [(2R)-oxolan-2-yl]methanol Substances 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 0.000 description 1
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
An injectable formulation containing a soluble salt of clavulanic acid and a soluble salt of an alpha -aminopenicillin or cephalosporin has its stability on reconstitution improved by the incorporation therein of glycofurol. The formulations may also contain a local anaesthetic e.g. lignocaine hydrochloride.
Description
SPECIFICATION
Pharmaceutical compositions
This invention relates to pharmaceutical compositions and, in particular, to anti-bacterial pharmaceutical compositions which may be administered by injection.
British Patent Specification No. 1,508,977 describes interalia clavulanic acid of formula (I):
and salts thereof, and the use of such compounds as synergists for penicillins and cephalosporins.
Synergistic formulations for injection comprising clavulanic acid or salts thereof are described in the aforementioned British Patent and in European
Patent Application Publication No. 0008905. Certain of these compositions tend to lose potency fairly quickly on reconstitution in the solvent for injection.
It is an object of this invention to provide an injectable pharmaceutical composition having improved stability relative to the previously known compositions.
Accordingly the present invention provides an injectable pharmaceutical composition, which composition comprises: (a) a water soluble salt of clavulanic acid; (b) a water soluble salt of an a-amino penicillin or cephalosporin: and (c) a vehicle of water and glycofurol.
In one aspect, the present invention provides an injectable pharmaceutical composition, which composition comprises a solution of: (a) a water soluble salt of clavulanic acid; (b) a water soluble salt of an a-amino penicillin or cephalosporin; and (c) a vehicle of water and glycofurol; and (d) optionally a local anaesthetic such as lignocaine or benzyl alcohol.
Glycofurol is the recognised term in the art for tetrahydrofurfuryl alcohol polyethylene glycol ether with an average of two ethylene glycol groups.
Glycofurol may be regarded as having the formula (ill):
wherein n is an integer from 1 to 4, preferably 1 or 2.
Suitably the glycofurol is 'Glycofurol 75' supplied by
Roche.
The ratio of glycofurol to water in the compositions of this invention is normally in the range 70:30 to 10:90, usually in the range 60:40 to 20:80, preferably in the range 50:50 to 20:80 for example approximately 50:50 or approximately 25:75 (these ratios are volume/volume). Of these 25:75 is preferred.
The ratio of anti-bacterial agents to vehicle present in the composition is normally from 2:15 to 7:15 usually 2:15 to 4:15, and generally approximates to 3:15. [These ratios are weight (taken as free acid equivalent weight)/volume].
The ratio of clavulanate salt to penicillin or cephalosporin salt present in the composition will normally be in the range 10:1 to 1 :10, usually in the range 1:1 to 1:8, and will preferably be 1:2 to 1 :5, for example 1:2. [These ratios are weight/weight ratios based on free acid equivalent weights].
Suitably the clavulanate salt will be the sodium or potassium salt, preferably the potassium salt.
Suitably the penicillin or cephalosporin salt is the sodium or potassium salt, preferably the sodium salt.
a-Amino penicillins and cephalosporins have a side-chain of structure (III):
wherein R is an organic radical of up to 20 carbon atoms. In formula (Ill), the -NH-group is attached to the 6-or 7-position of the penicillin or cephalosporin nucleus.
A particularly useful class of such penicillins and cephalosporins has R in structure (lli) being phenyl, p-hydroxyphenyl or cyclohexadienyl. Examples of such penicillins include ampicillin and amoxycillin, and of such cephalosporins include cephradine.
It has been found that this invention is particularly pertinent to formulations wherein the penicillin is amoxycillin.
The formulations of this invention are particularly applicable for penicillins and cephalosporins that show a tendency to dimerise in aqueous solution at pH values greater than 7.0. Such penicillins and cephalosporins include cephalexin, cephaloglycine and epicillin.
Thus one preferred embodiment of this invention is an injectable pharmaceutical composition comprising a solution of sodium or potassium clavulanate and sodium or potassium amoxycillin in a vehicle of water and glycofurol.
In these preferred embodiments the relative proportions of the ingredients are suitably as hereinbefore.
Most preferably in these embodiments the active ingredients are potassium clavulanate and sodium amoxycillin.
In another aspect, the invention also provides a twin pack in which the first part of the pack contains the active ingredients and the second part of the pack contains the vehicle.
The invention also provides a process for preparing the composition of the invention, which process comprises bringing into association the active ingredients and the vehicle.
The exact nature of this process, of course, varies with the nature of the compositions to be prepared.
When the composition is in solution form, then the process comprises dissolving the active ingredients (either simultaneously or consecutively) in the vehicle.
When the composition is in the twin pack form, then the process comprises filling the appropriate ingredients into separate parts of the pack.
The twin pack of this invention will generallycom- prise a vial containing the mixed active ingredients in the form of a dry powder and/or a freeze dried plug and a second vial or ampoule containing the mixed solvents. In order to form the injectable solution the liquid from the second vial will be transferred to the first vial.
The vial containing the active ingredients is con venientlyfilled by freeze drying a solution of the clavulanate salt in situ and thereafter adding to the resulting plug the penicillin or cephalosporin salt in powder form. These dry components may then be sealed into a vial. Alternatively the vial may be filled in a convenient conventional manner with separately prepared dry salts in powder form.
The injectable compositions of this invention may be used in the manner described in U.K. Patent No.
1,508,977.
In yet a further aspect, the invention provides a method of improving the stability of an aqueous injectable solution of a water soluble salt of clavulanic acid and a water soluble salt of an a-amino penicillin or cephalosporin which method comprises incorporating in the solution glycofurol as hereinbefore described.
The following Examples illustrate the invention.
Example 1
Amoxycillin (as the sodium salt) 250mg
Clavulanic Acid (as the potassium salt) 125mg
Lignocaine hydrochloride 20mg
Solvent (50% waterforinjection 50% glycofurol) to 2ml togo* amoxycillin 35 mins
clavulanic acid 45 mins *t,, is defined as the time taken for the component to degrade to 90% of its initial value.
Clavulanic Solvent Total t90 (mins) Example no Amoxycillin acid (%glycofurol/ Volume Clavulanic Amoxycillin (mug) (mug) % Water) (mI) I acid 2 250 125 0/100 2 8 12 3 250 125 50/50 1.5 30 20 4 250 125 50/50 3.0 75 95 5 250 125 30/70 2.5 40 35 6 250 125 40/60 2.0 40 30 7 500 100 0/100 3.5 5 10 8 500 100 50/50 3.5 40 70 9 250 125 25/75 1.8 17 28 10 500 125 25/75 3.5 15 39 Amoxycillin was used as the Sodium Salt.
Clavulanic acid was used as the Potassium Salt.
All samples included 1 % W/v lignocaine hydrochloride.
Claims (11)
1. An injectable pharmaceutical composition, which composition comprises: (a) a water soluble salt of clavulanic acid; (b) a water soluble salt of an a-amino penicillin or cephalosporin: and (c) a vehicle of water and glycofurol.
2. A pharmaceutical composition as claimed in claim 1 which comprises a local anaesthetic.
3. A pharmaceutical composition as claimed in either claim 1 o r claim 2 wherein the ratio of glycofurol: water is from 70:30 to 10:90.
4. A pharmaceutical composition as claimed in claim 3 wherein the ratio of glycofurol: water is approximately 25:75.
5. A pharmaceutical composition as claimed in any of claims 1 to 4 wherein the ratio of antibacterial agents to vehicle present is from 2:15 to 7:15 wt/vol.
6. A composition as claimed in any of claims 1 to 5 wherein the salt of clavulanic acid is sodium or potassium.
7. A composition as claimed in any of claims 1 to 6 wherein the penicillin or cephalosporin is selected from ampicillin, amoxycillin, epicillin, cephradine, cephalexin and cephaloglycine.
8. A pharmaceutical composition as claimed in any of claims 1 to 7 which composition comprises a solution of sodium or potassium clavulanate and sodium or potassium amoxycillin in a vehicle of glycofurol and water.
9. A twin pack in which the first part of the pack contains a water soluble salt of clavulanic acid and a water soluble salt of an o-amino penicillin or cephalosporin, and the second part of the pack contains a vehicle of glycofurol and water.
10. A method for improving the stability of an aqueous injectable solution of a water soluble salt of clavulanic acid and a water soluble salt of an a-amino penicillin or cephalosporin which method comprises the incorporation of glycofurol into the solution.
11. A process for preparing a pharmaceutical composition according to any of claims 1 to 8 which process comprises bringing into association the active ingredients and the vehicle.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8133767A GB2087721B (en) | 1980-11-20 | 1981-11-09 | Injectable antibiotic formulations stabilised with glycofurol |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8037235 | 1980-11-20 | ||
| GB8133767A GB2087721B (en) | 1980-11-20 | 1981-11-09 | Injectable antibiotic formulations stabilised with glycofurol |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB2087721A true GB2087721A (en) | 1982-06-03 |
| GB2087721B GB2087721B (en) | 1984-01-25 |
Family
ID=26277580
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB8133767A Expired GB2087721B (en) | 1980-11-20 | 1981-11-09 | Injectable antibiotic formulations stabilised with glycofurol |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB2087721B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004000358A1 (en) * | 2002-06-20 | 2003-12-31 | Amnon Sintov | Transdermal drug delivery system |
| US20090227549A1 (en) * | 2008-03-07 | 2009-09-10 | Scidose Llc | Fulvestrant formulations |
| US11179468B2 (en) | 2012-04-09 | 2021-11-23 | Eagle Pharmaceuticals, Inc. | Fulvestrant formulations |
-
1981
- 1981-11-09 GB GB8133767A patent/GB2087721B/en not_active Expired
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004000358A1 (en) * | 2002-06-20 | 2003-12-31 | Amnon Sintov | Transdermal drug delivery system |
| US20090227549A1 (en) * | 2008-03-07 | 2009-09-10 | Scidose Llc | Fulvestrant formulations |
| US9180088B2 (en) * | 2008-03-07 | 2015-11-10 | Scidose, Llc | Fulvestrant formulations |
| US9801892B2 (en) | 2008-03-07 | 2017-10-31 | Haz Two, Llc | Fulvestrant formulations |
| US10363259B2 (en) | 2008-03-07 | 2019-07-30 | Eagle Pharmaceuticals, Inc. | Fulvestrant formulations |
| US11179468B2 (en) | 2012-04-09 | 2021-11-23 | Eagle Pharmaceuticals, Inc. | Fulvestrant formulations |
| US12350339B2 (en) | 2012-04-09 | 2025-07-08 | Eagle Pharmaceuticals, Inc. | Fulvestrant formulations |
Also Published As
| Publication number | Publication date |
|---|---|
| GB2087721B (en) | 1984-01-25 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PCNP | Patent ceased through non-payment of renewal fee |