GB2063669A - Injectable solutions of sodium dicloxacillin - Google Patents

Injectable solutions of sodium dicloxacillin Download PDF

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Publication number
GB2063669A
GB2063669A GB8037236A GB8037236A GB2063669A GB 2063669 A GB2063669 A GB 2063669A GB 8037236 A GB8037236 A GB 8037236A GB 8037236 A GB8037236 A GB 8037236A GB 2063669 A GB2063669 A GB 2063669A
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GB
United Kingdom
Prior art keywords
pvp
dicloxacillin
molecular weight
compositions
composition
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
Application number
GB8037236A
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GB2063669B (en
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Beecham Group PLC
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Beecham Group PLC
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Filing date
Publication date
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Priority to GB8037236A priority Critical patent/GB2063669B/en
Publication of GB2063669A publication Critical patent/GB2063669A/en
Application granted granted Critical
Publication of GB2063669B publication Critical patent/GB2063669B/en
Expired legal-status Critical Current

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    • 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
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone

Abstract

A pharmaceutical composition, which on reconstitution with water yields an injectable solution, which composition comprises sodium dicloxacillin, and polyvinylpyrrolidone of molecular weight 1000 to 50,000.

Description

SPECIFICATION Injectable penicillin formulations This invention relates to an injectable penicillin formulation.
More specifically this invention relates to an injectable sodium dicloxacillin composition which has improved solubility at higher injection strengths and at lower temperatures.
Accordingly the present invention provides a pharmaceutical composition, which on reconstitution with water yields an injectable solution, which com position comprises sodium dicloxacillin, and polyvinylpyrrolidone of molecular weight 1000 to 50,000.
The polyvinyl pyrrolidone (hereinafter referred to as PVP) used in the composition of this invention has a molecular weight of from 1000 to 50,000. Since the material is a polymer it will be realised by a chemist that the molecular weight referred to is an average molecular weight. A suitable method of determining the average molecular weight of PVP for use in this composition is gel permeation chromatography. The PVP should not contain molecules with molecular weight of more than 60,000 similarly it should not have a monomer content of more than 1%. The K value of suitable PVP will generally be between 10 and 18.
Favourably the PVP employed will have a molecu larweight of 1000 to 12,000 more suitably 1500 to 6000.
A preferred PVP for use in the composition will have a molecular weight of 2000 to 3500. A PVP of this kind is Kollidon CE 5080 (Kollidon is a Registered Trade Mark) which is available from BASF Aktiengesselschaft, D-6700 Ludwigshafen, Federal Republic of Germany. This PVP has a K value of 12 to 14, which is a favoured range.
Normally the weight ratio of the dicloxacillin salt (taken as the free acid equivalent weight) to PVP in the compositions of the invention will be 10:1 to 1:5, more suitably 2:1 to 1:3.
The compositions of this invention may be reconstituted with an aqueous solvent, for example water, in conventional manner, the ingredients either being dissolved simultaneously or consecutively.
Normally sufficient composition will be dissolved to provide a solution containing 50 to 200 mg/ml of .s$icloxacillin (as free acid), more suitably 100 to 150 mg/ml.
One particularly useful aspect of the invention is an injectable solution containing 125 to 200 mg/ml of sodium dicloxacillin (as free acid), and PVP. Prefer ably such solutions contain 125 or 150 mg/ml of active ingredient.
The compositions ofthe invention may be presented in any convenient manner. For example a mixture of the sodium dicloxacillin and the PVP may be filled into a single container, such as a glass vial.
Alternatively the compositions may be presented as twin packs or the like, in which for example the sodium dicloxacillin and the PVP are in different parts of the pack -- in such an embodiment of course the PVP may be presented in aqueous solution so that the composition may simply be reconstituted by mixing together the parts of the pack.
It will be appreciated that as the compositions of the invention are to be used only after reconstitution into a solution, then the exact physical form of the dicloxacillin salt and the PVP in the (dry) compositions in unimportant although they will conveniently be in powder form.
The following Examples illustrate this invention.
EXAMPLE 1 The following Compositions were prepared by mixing together the stated ingredients in the stated proportions. The PVP used was Kollidon CE 5080 in Compositions 1 to 5 and Kollidon 30 (also available from BASF, molecularweight40000) in Compositions 6 and 7.
Composition Wt. of sodium Wt. of PVP Number dicloxacillin mg.
(p.f.a.), mg.
1 300 100 2 300 200 3 300 300 4 300 400 5 300 500 6 300 200 7 300 400 EXAMPLE2 The Compositions prepared in Example 1 were each dissolved in sufficient water to give 2 mls of clear solution having a sodium dicloxacillin concentration (as free acid) of 150 mg/ml.
1. A pharmaceutical composition, which on reconstitution with water yields an injectable solution, which composition comprises sodium dicloxacillin, and polyvinylpyrrolidone of molecular weight 1000 to 50,000.
2. A pharmaceutical composition as claimed in claim 1 wherein the polyvinylpyrrolidone has molecular weight of 1000 to 12000.
3. A pharmaceutical composition as claimed in claims 1 or 2 wherein the polyvinylpyrrolidone has molecular weight of 1500 to 6000.
4. A pharmaceutical composition as claimed in any one of claims 1 to 3 wherein the weight ratio of dicloxacillin salt to polyvinylpyrrolidone is in the range 10:1 to 1:5.
5. A pharmaceutical composition as claimed in any one of claims 1 to 4, wherein the weight ratio of dicloxacillin salt to polyvinylpyrrolidone is in the range 2:1 to 1:3.
6. A pharmaceutical composition as claimed in any one of claims 1 to 5, which on reconstitution with water provides an injectable solution containing 125-200 mg/ml of sodium dicloxacillin.
7. A pharmaceutical composition as claimed in any one of claims 1 to 6, which on reconstitution with water provides an injectable solution containing 125 - 150 mg/ml of sodium dicloxacillin.
8. A pharmaceutical composition as claimed in any one of claims 1 to 5 wherein thedicloxacillin salt
**WARNING** end of DESC field may overlap start of CLMS **.

Claims (8)

**WARNING** start of CLMS field may overlap end of DESC **. SPECIFICATION Injectable penicillin formulations This invention relates to an injectable penicillin formulation. More specifically this invention relates to an injectable sodium dicloxacillin composition which has improved solubility at higher injection strengths and at lower temperatures. Accordingly the present invention provides a pharmaceutical composition, which on reconstitution with water yields an injectable solution, which com position comprises sodium dicloxacillin, and polyvinylpyrrolidone of molecular weight 1000 to 50,000. The polyvinyl pyrrolidone (hereinafter referred to as PVP) used in the composition of this invention has a molecular weight of from 1000 to 50,000. Since the material is a polymer it will be realised by a chemist that the molecular weight referred to is an average molecular weight. A suitable method of determining the average molecular weight of PVP for use in this composition is gel permeation chromatography. The PVP should not contain molecules with molecular weight of more than 60,000 similarly it should not have a monomer content of more than 1%. The K value of suitable PVP will generally be between 10 and 18. Favourably the PVP employed will have a molecu larweight of 1000 to 12,000 more suitably 1500 to 6000. A preferred PVP for use in the composition will have a molecular weight of 2000 to 3500. A PVP of this kind is Kollidon CE 5080 (Kollidon is a Registered Trade Mark) which is available from BASF Aktiengesselschaft, D-6700 Ludwigshafen, Federal Republic of Germany. This PVP has a K value of 12 to 14, which is a favoured range. Normally the weight ratio of the dicloxacillin salt (taken as the free acid equivalent weight) to PVP in the compositions of the invention will be 10:1 to 1:5, more suitably 2:1 to 1:3. The compositions of this invention may be reconstituted with an aqueous solvent, for example water, in conventional manner, the ingredients either being dissolved simultaneously or consecutively. Normally sufficient composition will be dissolved to provide a solution containing 50 to 200 mg/ml of .s$icloxacillin (as free acid), more suitably 100 to 150 mg/ml. One particularly useful aspect of the invention is an injectable solution containing 125 to 200 mg/ml of sodium dicloxacillin (as free acid), and PVP. Prefer ably such solutions contain 125 or 150 mg/ml of active ingredient. The compositions ofthe invention may be presented in any convenient manner. For example a mixture of the sodium dicloxacillin and the PVP may be filled into a single container, such as a glass vial. Alternatively the compositions may be presented as twin packs or the like, in which for example the sodium dicloxacillin and the PVP are in different parts of the pack -- in such an embodiment of course the PVP may be presented in aqueous solution so that the composition may simply be reconstituted by mixing together the parts of the pack. It will be appreciated that as the compositions of the invention are to be used only after reconstitution into a solution, then the exact physical form of the dicloxacillin salt and the PVP in the (dry) compositions in unimportant although they will conveniently be in powder form. The following Examples illustrate this invention. EXAMPLE 1 The following Compositions were prepared by mixing together the stated ingredients in the stated proportions. The PVP used was Kollidon CE 5080 in Compositions 1 to 5 and Kollidon 30 (also available from BASF, molecularweight40000) in Compositions 6 and 7. Composition Wt. of sodium Wt. of PVP Number dicloxacillin mg. (p.f.a.), mg. 1 300 100 2 300 200 3 300 300 4 300 400 5 300 500 6 300 200 7 300 400 EXAMPLE2 The Compositions prepared in Example 1 were each dissolved in sufficient water to give 2 mls of clear solution having a sodium dicloxacillin concentration (as free acid) of 150 mg/ml. CLAIMS
1. A pharmaceutical composition, which on reconstitution with water yields an injectable solution, which composition comprises sodium dicloxacillin, and polyvinylpyrrolidone of molecular weight 1000 to 50,000.
2. A pharmaceutical composition as claimed in claim 1 wherein the polyvinylpyrrolidone has molecular weight of 1000 to 12000.
3. A pharmaceutical composition as claimed in claims 1 or 2 wherein the polyvinylpyrrolidone has molecular weight of 1500 to 6000.
4. A pharmaceutical composition as claimed in any one of claims 1 to 3 wherein the weight ratio of dicloxacillin salt to polyvinylpyrrolidone is in the range 10:1 to 1:5.
5. A pharmaceutical composition as claimed in any one of claims 1 to 4, wherein the weight ratio of dicloxacillin salt to polyvinylpyrrolidone is in the range 2:1 to 1:3.
6. A pharmaceutical composition as claimed in any one of claims 1 to 5, which on reconstitution with water provides an injectable solution containing 125-200 mg/ml of sodium dicloxacillin.
7. A pharmaceutical composition as claimed in any one of claims 1 to 6, which on reconstitution with water provides an injectable solution containing 125 - 150 mg/ml of sodium dicloxacillin.
8. A pharmaceutical composition as claimed in any one of claims 1 to 5 wherein thedicloxacillin salt and the polyvinylpyrrolidone are in powder form.
GB8037236A 1979-11-27 1980-11-20 Injectable solutions of sodium dicloxacillin Expired GB2063669B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
GB8037236A GB2063669B (en) 1979-11-27 1980-11-20 Injectable solutions of sodium dicloxacillin

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB7940908 1979-11-27
GB8037236A GB2063669B (en) 1979-11-27 1980-11-20 Injectable solutions of sodium dicloxacillin

Publications (2)

Publication Number Publication Date
GB2063669A true GB2063669A (en) 1981-06-10
GB2063669B GB2063669B (en) 1984-02-15

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Family Applications (1)

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GB8037236A Expired GB2063669B (en) 1979-11-27 1980-11-20 Injectable solutions of sodium dicloxacillin

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GB (1) GB2063669B (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0125725A1 (en) * 1983-05-09 1984-11-21 Gist-Brocades N.V. Oxytetracyclin solutions

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0125725A1 (en) * 1983-05-09 1984-11-21 Gist-Brocades N.V. Oxytetracyclin solutions

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Publication number Publication date
GB2063669B (en) 1984-02-15

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