GB2388025A - Kit for preparing a formulation of paclitaxel - Google Patents
Kit for preparing a formulation of paclitaxel Download PDFInfo
- Publication number
- GB2388025A GB2388025A GB0207991A GB0207991A GB2388025A GB 2388025 A GB2388025 A GB 2388025A GB 0207991 A GB0207991 A GB 0207991A GB 0207991 A GB0207991 A GB 0207991A GB 2388025 A GB2388025 A GB 2388025A
- Authority
- GB
- United Kingdom
- Prior art keywords
- solution
- paclitaxel
- cremophor
- kit
- citric acid
- 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.)
- Withdrawn
Links
Classifications
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Abstract
A kit for preparing a pharmaceutical formulation of Paclitaxel, whereby the individual ingredients are supplied in separate, sterilely sealed containers. The formulation is chemically, pharmaceutically, and also microbiologically stable.
Description
Kit for Preparing a Formulation of Paclitaxel The invention relates to a
kit for preparing a pharmaceutical formulation of Paclitaxel. Paclitaxel is a naturally occurring compound which can be isolated from yews or yew bark. The active substance posse sees cytostatic and cytotoxic properties and is the main ingredient of pharmaceutical products used in cancer therapy.
Treatment with Paclitaxel has, for example, been described for ovarian cancer (cf. inter alla, McGuire et al., Ann. Int. Med. 111, 273 -279 (1989)), breast cancer (cf. inter alla, Holmes et al., Proceedings of the American Society of Clinical Oncology, Vol. 10, p. 60), lung cancer (cf. inter alla, Brown et al., J of Clin Oncol, Vol. 9, No. 7, pp. 1261-1267), and leukemia (cf. inter alla, Rowinsky et al., Cancer Research 49, 4640 4647).
Paclitaxel itself is not readily soluble in water, so it is difficult to prepare a proper formulation which can then be further diluted with aqueous infusion solutions (e.g. 0.9% NaCI solution). Furthermore, because of its responsivity to water and alkalis, Paclitaxel is also not sufficiently stable in lipophilic solvents, e.g. polyethoxylated castor oil, such as Cremophor EL or Cremophor ELP@, or in alcoholic solvents, such as ethanol.
The problem behind the invention is to supply Paclitaxel in such a way that the aforementioned stability problems are avoided and the form of preparation necessary for administration to the patient can be prepared quickly and simply.
( 2 The problem of the invention was solve d by developing a kit for the preparation of a form With a defined composition which can be administered as a pharmaceutical. Thus, the object of the invention is a kit for the preparation of a pharmaceutical formulation of Paclitaxel, characterized in th at a defined quantity of Paclitaxel is supplied in one sterilely sealed vial, a defined solution of citric acid anhydride in ethanol (solution A) in a second sterilely sealed vial, and a defined solution of Cremophor ELF or Cremophor ELAN in absolute ethanol (solution B) in a third sterilely sealed vial.
The medication prepared with this method represents a dearly costeffective alternative to the manufactured pharmaceutical products currently on the market with the ingredient Paclitaxel.
Stability problems during lengthy storage of the solution are avoided by supplying the active substance, the solvent, and the stabilizer separately. The dissolved form of the active substance is prepared immediately before its use by the pharmacist or doctor.
The active substance Paclitaxel is supplied in a precisely defined quantity in the first sterilely sealed vial.
The vial is appropriately sized to take in corresponding quantities of solution A and solution B during the preparation of the solution.
The active substance Paclitaxel is present in the first vial in a precisely defined quantity. This allows the preparation of, for example, exactly 30 mg, 100 mg, 300 mg, 500 mg, 1000 mg, 2000 mg, 3000 me, or more of Paclitaxel.
Paclitaxel is only dissolved when shaken after a defined quantity of solution A has been added. It is not normally necessary to heat the mixture; however, the mixture may be heated by the warmth of the preparer's hands in order to accelerate the dissolution process.
Solution A consists of anhyd rous citric acid (or citric acid anhydride) and absolute ethanol, whereby 970 mg of citric acid (or citric acid anhydride) are dissolved in 70.6 mg of absolute ethanol (=89.4 ml).
A defined quantity of solution B is then added, and the mixture is shaken u ntil the solution becomes homogenous.
Solution B consists of a mixture of Cremophor EL or Crernophor ALPS (BASE Company), which has also been purified by hypercritical fluids if necessary, whereby 258.8 mg of Cremophor and 123.5 mg of ethanol (=156.4 ml) are present in the vial.
The vials are made of glass or a chemically inert material and are sterilely sealed.
3 ml of solution A and 14 ml of solution B are used per 100 mg of Paclitaxel.
Multiples or fractions of these solvents are used as appropriat e for the larger quantities of Paclitaxel indicated above.
The formulation of Paclitaxel prepared in this manner is chemically, pharmaceutically, and also microbiologically stable for at least one year.
Additional preparation for infusion into the patien t is performed by diluting the Paclitaxel concentrate prepared in this manner with the usual infusion solutions.
Example 1:
3 ml of solution A are added to 100 mg of Paclitaxel in the first vial, and Paclitaxel is dissolved in this solution by shaking. 14 ml of solution B are then added, and the mixture is shaken until it is homogenous.
The concentrate can now be processed further to prepare an infusion solution.
It is also possible to store this Paclitaxel concentrate for at least 1 year.
Example 2:
9 ml of solution A are added to 300 mg of Paclitaxel in the first vial, and Paclitaxel is dissolved in this solution by shaking. 52 ml of solution B are then added, and the mixture is shaken until it is homogenous.
The concentrate can now be processed fur ther to prepare an infusion solution.
It is also possible to store this Paclitaxel concentrate for at least 1 year.
Claims (1)
- ( s Patent Claims:1) Kit for the preparation of a stable pharmaceutical formulation of Paclitaxel, characterized in that a defined quantity of Paclitaxel is supplied in one sterilely sealed vial, a defined solution of anhydrous citric acid (citric acid anhydride) in ethanol (solution A) in a second sterilely sealed vial, and a defined solution of Cremophor ELF or Cremophor ALPS in ethanol (solution B) in a third sterilely sealed vial.2) Kit according to Claim 1, characterized in that 30 mg, 100 mg, 300 mg, 500 mg, 1000 mg, 2000 mg, 3000 mg, or more of Paclitaxel is supplied in the first vial.3) Kit according to either Claim 1 or 2, characterized in that solution A consists of mg of anhydrous citric acid (citric acid anhydride) in 70.6 mg of absolute ethanol. 4) Kit according to any one of the preceding Claims 1 through 3, characterized in that solution B consists of 258.8 mg of Cremophor EL or Cremophor ELBA which may be purified by hypercritical fluids if necessary, in 123.5 mg of absolute ethanol.5) Method for preparing a pharmaceutical formulation of Paclitaxel by dissolving a defined quantity of Paclitaxel in a defined volume of solution A by shaking, and then adding a defined volume of solution B and shaking the mixture until it becomes( 6 homogenous. 6) Method according to Claim 5, characterized in that 3 ml of so lotion A and 14 ml of solution B are used per 100 mg of Taxol.7) Pharmaceutical formulation of Paclitaxel prepared by one of the methods according to Claims 5 or 6.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0207991A GB2388025A (en) | 2002-04-06 | 2002-04-06 | Kit for preparing a formulation of paclitaxel |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0207991A GB2388025A (en) | 2002-04-06 | 2002-04-06 | Kit for preparing a formulation of paclitaxel |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB0207991D0 GB0207991D0 (en) | 2002-05-15 |
| GB2388025A true GB2388025A (en) | 2003-11-05 |
Family
ID=9934387
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB0207991A Withdrawn GB2388025A (en) | 2002-04-06 | 2002-04-06 | Kit for preparing a formulation of paclitaxel |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB2388025A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007036792A3 (en) * | 2005-09-29 | 2007-08-30 | Novachem S A | Kit for parenteral administration of medicaments |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19925211A1 (en) * | 1999-06-01 | 2000-12-07 | Pbs Pharmaceutical Bulk Substa | Kit for preparing stable paclitaxel formulation for use as anticancer agent, comprising separately stored drug, solution of anhydrous citric acid in ethanol and solution of polyethoxylated castor oil in ethanol |
-
2002
- 2002-04-06 GB GB0207991A patent/GB2388025A/en not_active Withdrawn
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19925211A1 (en) * | 1999-06-01 | 2000-12-07 | Pbs Pharmaceutical Bulk Substa | Kit for preparing stable paclitaxel formulation for use as anticancer agent, comprising separately stored drug, solution of anhydrous citric acid in ethanol and solution of polyethoxylated castor oil in ethanol |
Non-Patent Citations (1)
| Title |
|---|
| WPI Abstract Accession No 2001-062579/08 & DE019925211 (PHARMACEUTICAL BULK SUBSTANCES) * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007036792A3 (en) * | 2005-09-29 | 2007-08-30 | Novachem S A | Kit for parenteral administration of medicaments |
| JP2009509608A (en) * | 2005-09-29 | 2009-03-12 | インファ ソシエテ アノニム | Kit for parenteral administration of drugs |
| US8182449B2 (en) | 2005-09-29 | 2012-05-22 | Infa, S.A. | Kit for parenteral administration of medicaments |
Also Published As
| Publication number | Publication date |
|---|---|
| GB0207991D0 (en) | 2002-05-15 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |