IE47126B1

IE47126B1 - An injectable chloramphenicol composition

Info

Publication number: IE47126B1
Application number: IE1425/78A
Authority: IE
Original assignee: Abic Ltd
Priority date: 1977-07-15
Filing date: 1978-07-14
Publication date: 1983-12-28
Also published as: NL7807641A; NZ187683A; ZA783671B; DE2829408A1; IL52533A; AU3752578A; ATA511878A; FR2397191A1; IL52533A0; IE781425L; GB2000970A; AT360149B; JPS5420125A; FR2397191B1; GB2000970B; CA1112572A; BE869001A

Abstract

An injectable composition contains chloramphenicol, N-methylpyrrolidone and polyvinyl-pyrrolidone. The composition may also contain a pharmaceutically-acceptable solvent which is miscible with N-methylpyrrolidone. It is used in veterinary medicine and is stable, concentrated, exhibits constant blood levels and does not produce unpleasant side effects.

Description

The present invention relates to a stable injectable chloramphenicol composition having a high content of chloramphenicol.

Cnloramphenicol is stilise·' at present mainly for 5 veterinary purposes. It is desired to administer to a large animal a composition having a rather high content of chloramphenicol. Said large amount of chloramphenicol should exhibit constant clood levele and be active for quite a long period of time. So far there has been injected sodium succinate of chloramphenicol in a concentration of 25% and there are also known some injectable compositions which comprise up to 25% of active compound. However, these compositions are not always satisfactory, i.e. in particular they are unstable and have a relatively short shelf life, and it was therefore desirable to develop compositions which would have higher concentrations of chloramphenicol and would have the desired properties, i.e. exhibit constant blood, levels and have a long shelf life.

It has been foud that if chloramphenicol is dissolved in N-methylpyrrolidone there may be prepared compositions having a higher concentration of chloramphenicol(about 50%). However, these compos tions had the following drawbacks: a. Erratic blood lelre .s were obtained^ b. rain and irritation were caused to the animal treated with said injection. - 2 •· 4 7 12 6 For these reasons said compisitince were not applicable. It has now surprisingly been found that with the addition of a certain amount of polyvinyl pyrrolidone(PVP) to said composition said drawbacks are overcome. This is surprising ae it could not he expected that PVP- would cause a constant blood level and in particular that it would dispel the pain and irritation. The shelf life of said compositions is at least one year.

The present invention thus consists in an injectable 10 composition comprising chloramphenicol, N-methylpyrrolidone, PVP and, if desired, a pharmaceutically acceptable solvent which is miscible wish N-methylpyrrolidone.

Compositions according to the present invention may comprise also, if desired, only small amounts of chloramphe15 nicol. However, they should contain preferably at least 30# of chloramphenicol and especially 4Q-6O#(all percentages are given herein weight/volume). Compositions according to the present Invention having a lower content of chloramphenicol are also much better than those commercially available as 2ti they are much more stable.

The amount of the PVP varies and it should be between 4-20# preferably between 5-10# of the entire composition.

Other solvents, if required, are utilised ae diluents in order to get the required concentration of the composition.

As suitable solvent?; one should mention water, ethanol and ln particular, certain glycols, or derivatives thereof, e.g. propyleueglycoi, glycerol-formal, tertaglycol, polyethyleneglycol, etc. 126 The present invention will now be illustrated with reference to the following examples without being restricted by them.

The composition of the present invention were prepared as follows in all examples: ihe chloramphenicol was dissolved in N-methylpyrrolidone. Thereafter the PVP was adder ana finally the additional solvent, if any, was admixed.

The PVP utilised is a product of General Aniline and Film Corporation.The K numbers are derived from viscosity.

Example 1 Chloramphenicol 50«0 g N-Methylpyrrolidone 40.0 g PVP K50 6.0 g Propyleneglycol enough to make 100.0 ml At the end of two years storage at room temperature had only 5.5% of the chloramphenicol/degraded.

The volume needed of thi composition (called the 50% composition) to be injected to a ruminant for achieving a d06e level cf SO mg/kg was compared with the following composition: Chloramphenicol 20 g Glycerolformal 80 g «i&ter enough to make 100 ml The shelf life cf the 20?· composition was less than 2 months (the degradation of chloramphenicol was about 40%).

The results are given in Table 1, wh t.ch show comparitive blood levels of chloramphenicol after parenteral administration of 50 mg/kg of each of the compositions. 7 12 6 - 4 TABLE 1 Formulation Calf of 50 kg Ewe of 65 kg Cow of 500 kg Cow of 650 kg 20% 12.5 ug/ml 16.25 ug/ml 125 ug/ml 162.5 ug/ml 50$ 5 ug/ml 6.5 ug/ml 50 ug/ml 65 ug/ml Similar comparisons with compositions having various concentrations of chloramphenicol showed the superiority of the 50$ composition.

Moreover, the mean serum chloramphenicol concentrations over a certain period of time following a single intramuscular injection of said formulations were compared.

The results are shown in the accompanying drawings in which: Fig.l shows the mean serum concentration of c&lves at a dose level of 50 mg/kg.

Pig.2 shows the mean serum concentration at cows at a dose level of 30 mg/kg; and Fig.3 shows the mean eerum concentration of ewes at 15 at a dose level of 50 mg/kg.

The tests were performed by known methods (see, for example, Glazko,(e), Set.al. Arch. Biochero. 23 . 411-418,1949 and Ziv.b, et al. Zbl.Vet.Med.(A) 20,801-811.1973).

Example 2 Chloramphenicol 10.0 g N-Methylpyrrolidine 30.0 g PVP K15 6.0 g Propyleneglycol enough to make 100.0 ml 1 an Example 5 Ohioram ph βnic oi FVP XI5 §0.0 ;; 0.0 g N-ftethylpyrrolidone enough: to make 100.0 ml Mtople 4 Chloramphenicol N-Methylpyrrcliuone FVF K30 Glyceroli'ormal enough to make Example 5Chloramphenicol N-Methylpyrrolidone FVF K30 Tetraglycol enough to make Example b Chloramphenicol h-Me thylpy rro1id one PVF K15 Polyethyleneglycol 500 enough Example *? Chloramphenicol fl-Methylpyrrolidone FVF K15 Ethanol 951 enough to make 50.0 R 40.0 g 1C.0 g 100.0 ml 50.0 g 40.0 g 1.0 fi 100.0 ml 40.0 g 40.0 g .0 g o make 100.0 ml .0 g 40.0 g 20.0 g 100.0 ml.

Example 6 Chloramphenicol k-Methylpyrrolidone PVF KL5 water enough to make 100 ml

Claims

1. An injectable composition comprising chloramphenicol, N-methylpyrrolidone, PVP and, if aesired, a pharmaceutically acceptable solvent which is miscible with N-methylpyrrolidone.

2. A composition according to Claim 1 wherein the amount of chloramphenicol is at least 5. A composition according to Claim 1 or 2, wherein the amount of chloramphenicol is 40-60¾.

3. 4. A composition according to any of Claims 1 to 3, wherein the amount of PVT is 4-20?«.

4. 5. A composition according to Claim 4, wherein the amount of PVP is 5-10%.

5. 6. A composition according to any of Claims 1 to 5 wherein the additional solvent is water.

6. 7. A composition according to any of Claims 1 to 5 wherein the additional solvent is ethanol.

7. 8. A composition according to any of Claims 1 to 5 wherein the additional solvent is a glycol or a derivative thereof.

8. 9. A composition according to Claim 8, wherein the glycol is selected among the group comprising propyleneglycol, glycerolformal, tertraglycol, polyethyleneglycol.

9. 10. An injectable composition, substantially as hereinbefore described with reference to the Examples.

10.

11. A method for the preparation of an injectable composition as defined in Claim 1, wherein the chloramphenicol is dissolved in the N-methylpyrrolidone, PVP is solution and the additional solvent, if any,