INJECTABLE FORMULATIONS OF PARACETAMOL

Abstract

The present invention relates to low volume intravenous injections of paracetamol or its pharmaceutically acceptable salt and method of preparation thereof. The formulations provide high concentration of paracetamol or its pharmaceutically acceptable salt in a solvent system of the present invention which can be administered not only through intra-muscular & intravenous infusion route but also suitable for slow IV bolus administration after dilution with aqueous fluids to final volume of not more than 20 ml. These injectable formulations remain stable and are also suitable for administration through slow intravenous route with minimized side effects (such as phlebitis, pain etc.).

Claims

1. An injectable formulation of Paracetamol comprising: 250 mg/ml Paracetamol or pharmaceutically acceptable salts thereof in a solvent system comprising glycofurol, a lower chain alcohol, a stabiliser, another solvent and water.

2. The injectable formulation of claim 1, wherein the viscosity of the formulation ranges from 5 to 35 CPs at 25° C.

3. The injectable formulation of claim 1, wherein the solvent system comprises 0-40% w/v glycofurol 0-30% w/v lower chain alcohol 0-5% w/v stabiliser 0-55% of the other solvent and water to make up the volume of the formulation.

4. The injectable formulation of claim 1, wherein the other solvent is selected from Surfactants, Cyclodextrins, Dimethylacetamide derivatives, Transcutol, N-Methyl Pyrollidone, polyhydric alcohol(s), or mixtures thereof.

5. The injectable formulation of claim 4, wherein the other solvent is selected from Surfactants, Cyclodextrins, Dimethylacetamide derivatives, Transcutol, or N-Methyl Pyrollidone.

6. The injectable formulation of claim 1, wherein the lower chain alcohol is selected from ethyl alcohol, iso-propyl alcohol and their like, or mixtures thereof.

7. The injectable formulation of claim 3, wherein the amount of water is <50% v/v, of the formulation.

8. The injectable formulation of claim 7, wherein the formulation further comprises auxiliary ingredients such as antioxidant(s), pH modifier(s), buffer(s), chelating agent(s), or any mixtures thereof.

9. The injectable formulation of claim 8, wherein the antioxidant(s) of the formulation is selected from Monothioglycerol, sodium metabisulphite, or their like.

10. The injectable formulation of claim 8, wherein the pH modifier(s) of the formulation is selected from Sodium Hydroxide, hydrochloric acid, or their like.

11. The injectable formulation of claim 8, wherein the buffer(s) of the formulation is selected from Dibasic sodium phosphate, monobasic sodium phosphate, or their like.

12. The injectable formulation of claim 1, wherein the formulation is diluted with the help of water for injection, or conventional aqueous IV fluids such as normal saline, dextrose solution, or any other parenteral carriers, a dose of 1 gm of Paracetamol or its pharmaceutically acceptable salt is delivered in 20 ml volume of the final formulation, and no crystals appear for a period of at least 5 to 8 minutes.

13. The injectable formulation of claim 12, wherein the formulation is capable of administration via intra-muscular, intra-venous bolus, intravenous infusion and slow intra-venous bolus injection.

14. The injectable formulation of claim 13, wherein the slow intra-venous bolus injection is stable from 2 to 10 minutes after dilution of the formulation.

15. The injectable formulation of claim 2, wherein the viscosity of the formulation ranges from 8 to 32 CPs at 25° C.

16. The injectable formulation of claim 4, wherein the polyhydric alcohol(s) is selected from Propylene Glycol, Glycerine, Sorbitol and Polyethylene glycol, or mixtures thereof.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0028] The present invention provides stable high concentration aqueous injections of paracetamol or its pharmaceutically acceptable salts, which when diluted with aqueous fluids to not more than 20 ml, remain stable and are suitable for administration through slow intravenous route.

[0029] An injectable formulation of the present invention comprises 250 mg/ml paracetamol or its pharmaceutically acceptable salt, a solvent system comprising Glycofurol and/or another solvent, Lower chain alcohol, a stabiliser, and water.

[0030] The other solvent is selected from Surfactants, Cyclodextrins, Dimethylacetamide derivatives, Transcutol, N-Methyl Pyrollidone, or polyhydric alcohol(s) such as Propylene Glycol, Glycerine, Sorbitol and Poly ethylene glycols may be used.

[0031] The other solvent is preferably selected from N-methyl pyrollidone, Dimethylacetamide, Transcutol, Cyclodextrins, or mixtures thereof.

[0032] The amount of glycofurol in the formulations ranges from 0 to 40% w/v, preferably 0 to 35% w/v of the formulation. The amount lower chain alcohol ranges from 0 to 30% w/v, preferably 0 to 25% w/v of the formulation. The amount of the other solvent in the formulations ranges from 0 to 55% v/v of the formulation.

[0033] The stabiliser is selected from grades of polymeric compounds such as Plasdone for example Plasdone C 17, Plasdone C 30 and their like or any combination thereof. The stabiliser is 0% w/v to 5% w/v, preferably 2% w/v to 4% w/v of the formulation.

[0034] In one embodiment the injectable containing 250 mg paracetamol or its pharmaceutically acceptable salt in 1 ml. In another embodiment, the dose of 500 mg of drug can be delivered in a volume of 2 ml. In another embodiment, the dose of 1 gm can be delivered in a volume of 4 ml. These embodiments are suitable for administration through the Intramuscular route.

[0035] In one of the embodiments, these formulations when diluted using low volume of aqueous fluids, can deliver the therapeutic dose of 1 gm of Paracetamol or its pharmaceutically acceptable salt in 20 ml of the formulation without any recrystallization for at least up to 5 minutes after dilution, In another embodiment, such formulations do not exhibit recrystallization in at least 8 to 20 minutes after dilution.

[0036] The aqueous fluids for dilution are selected from water for injection or any other medicated/non-medicated aqueous fluids suitable for slow IV bolus administration. These formulations also provide the option of dilution with large volume of aqueous fluids in order to deliver the drug through intravenous infusion route.

[0037] These formulations result in complete solubilisation of Paracetamol or its pharmaceutically acceptable salt. The formulations containing 1 gm of drug when diluted with aqueous fluids up to 20 ml, do not exhibit and recrystallization at least up to 5 minutes after dilution, more preferably up to a period of at least 8 minutes after dilution

[0038] Injectable formulations comprising 250 mg/ml of paracetamol or its pharmaceutically acceptable salt, the solvent system of the present invention with a stabiliser in a specified range provides injectable formulations which on dilution with aqueous fluids up to 20 ml of formulation, are suitable for slow IV bolus route of administration with significantly minimised side effects such as phlebitis.

[0039] The formulations of the present invention are stable throughout the shelf life of the formulations. In the present invention, water is used in a quantity sufficient to make up the final volume of the formulation. Water to make up the final volume in these formulations is less than or equal to 50% w/v, preferably less than or equal to 45% w/v of the formulations.

[0040] The said formulations of the present invention can further be diluted with the help of water for injection or conventional aqueous IV fluids such as normal saline, dextrose solution or any other parenteral carriers known in the art such that a dose of 1 gm of Paracetamol or its pharmaceutically acceptable salt is delivered in 20 ml volume of the final formulation.

[0041] In another embodiment of the present formulations, suitable auxiliary ingredients such as antioxidant(s), pH modifier(s), buffer(s), chelating agent(s), or mixtures thereof may be used. The antioxidant(s) of the formulation can be selected from Monothioglycerol, sodium metabisulphite, or their like. The pH modifier(s) the formulation can be selected from Sodium Hydroxide, hydrochloric acid, or their like. The buffer(s) of the formulation can be selected from Dibasic sodium phosphate, monobasic sodium phosphate, or their like.

[0042] The said auxiliary ingredients are used in the pharmaceutically acceptable proportions known in the art.

[0043] The viscosity of the present formulations in their undiluted form is in the range of 5 to 35 CPS when measured by Ostwald viscometer at 25° C. The viscosity of the preferred embodiments of the present formulations in their undiluted form ranges from 8 to 32 CPs at 25° C. This feature of the formulations of the present invention not only provides the advantage of less or no pain and no tissue damage at the site of injection when administered in undiluted form intra-muscularly but also leads to less or no pain when administered upon dilution up to 20 ml via slow IV bolus route over a period of 2 to 5 minutes.

[0044] The applicant conducted pre-clinical (animal) toxicity studies to establish the above mentioned advantageous features of the formulation of the present invention. The said studies and results thereof are summarised as under.

[0045] Sub-acute toxicity study of Undiluted Paracetamol injection (1000 mg/4 ml) in rats and mice:

[0046] The study was aimed to assess toxicity of paracetamol injection 1000 mg/4 ml (250 mg/ml) in rats and mice after repeated administration for 28 days. The animals were selected, conditioned, and exposed administered the test compound through Intra venous undiluted bolus injection at three dosage levels (15, 25, 35 mg/kg) and observed for 28 days.

[0047] All animals were observed for abnormal clinical signs and behavioral changes; morbidity and mortality; changes in body weight and food consumption throughout the study period. At the end of study (i.e. 28 days), the animals were also evaluated for hematological and biochemical estimations and histopathology of different organs for determination of toxicity.

[0048] The results showed that there were no mortalities observed among the animals treated due to test compound. There was no significant treatment effect on food intake, body weight gain and clinical signs, behavioural activity etc. Further, there were no significant changes found in haematological and biochemical parameters of mice and rats treated with all three dose levels of paracetamol as compared to control vehicle group.

[0049] The result concluded that surprisingly no toxicity was observed in rats and mice when undiluted Paracetamol formulation (1000 mg/4 ml) was injected by intravenous bolus route of administration. This is in contrast with the results of the study conducted for the formulations in WO2012001494 which were not tolerated through IV bolus route even at low dose.

Repeated Dose Toxicity Study of Paracetamol Injection (1000 mg/4 ml) in Rabbits

[0050] The objective of this study was to assess the local and systemic toxicity in rabbits from 14 days repeated administration of Paracetamol Injection (1000 mg/4 ml), prepared as per the present invention with a special emphasis on identifying target organs toxicities.

[0051] In this study, animals were randomly assigned to four treatment groups. Each group comprised of two female rabbits. Two groups (01 & 02) were given vehicle (Placebo) for Paracetamol Injection (1000 mg/4 ml) diluted up to 20 ml with water for injection. Other two groups (03 & 04) were given Paracetamol Injection (1000 mg/4 ml) diluted up to 20 ml with water for injection. 01 & 03 groups were treated with their respective treatments as once a day dose at volume of 2.52 ml/2 Kg Rabbit. 02 & 04 groups were treated with their respective treatments in divided doses administered four times a day (0.63 ml/2 Kg each time). The diluted injections were administered as slow intravenous infusion at 65 mg/kg dose level within 2 to 5 minutes.

[0052] All the animals were observed once a day for signs of toxicity throughout the experimental period and twice daily for mortality and morbidity. Body weights were recorded on Day 1, 8, and 14. Feed consumption was calculated on weekly basis. At the end of experiment (Day 14), all surviving animals were sacrificed and gross pathology data was recorded.

[0053] At the end of study (i.e. 14 days), the animals were evaluated for gross pathology and histopathology of different organs including site of injection for determination of toxicity. The result showed no local or systemic toxicity with Paracetamol injection 1000 mg/4 ml when administered as intravenous infusion in diluted form with water for injection for 14 days in rabbits.

[0054] The results of the preclinical studies conducted by the applicant confirmed that the formulations of the present invention are capable of being administered through IV bolus route of administration in their undiluted form as well as through slow IV bolus route of administration over 2 to 5 minutes when diluted with water for injection to a final volume up to 20 ml.

[0055] Non-limiting examples of the formulations of the present invention are provided herein below

Example 1

[0056]

TABLE-US-00002 Ingredients Amount (mg/ml) Percentage % Paracetamol 250 25% w/v Glycofurol 353 35.3% w/v Ethyl alcohol 240 24% w/v Plasdone C 17  20 2% w/v Water for Injection Qs to 1 ml Qs to 100%

[0057] The viscosity of the above formulation (undiluted) was 18 CPS when measured by Ostwald viscometer at 25° C.

[0058] When 4 ml (Volume equivalent to 1 gm) of the above formulation was diluted with water for injections up to a final volume of 20 ml, no recrystallization of drug was observed at 25° C. up to duration of 8 minutes after dilution and at 20° C. up to duration of 5 minutes after dilution.

Example 2

[0059]

TABLE-US-00003 Ingredients Amount (mg/ml) Percentage % Paracetamol 250 25% w/v Glycofurol 300 30.0% w/v Ethyl alcohol 300 30% w/v Plasdone C 30  25 2.5% w/v Water for Injection Qs to 1 ml Qs to 100%

[0060] The viscosity of the above formulation (undiluted) was 15 CPS when measured by Ostwald viscometer at 25° C.

[0061] When 4 ml (Volume equivalent to 1 gm) of the above formulation was diluted with water for injections up to a final volume of 20 ml, no recrystallization of drug was observed at 25° C. up to duration of 8 minutes after dilution and at 20° C. up to duration of 5 minutes after dilution.

Example 3

[0062]

TABLE-US-00004 Ingredients Amount (mg/ml) Percentage % Paracetamol 250 25% w/v Glycofurol 353 35.3% w/v Ethyl alcohol 240 24% w/v Plasdone C 17  30 3% w/v Water for Injection Qs to 1 ml Qs to 100%

[0063] The viscosity of the above formulation (undiluted) was 19.46 CPS when measured by Ostwald viscometer at 25° C.

[0064] When 4 ml (Volume equivalent to 1 gm) of the above formulation was diluted with water for injections up to a final volume of 20 ml, no recrystallization of drug was observed at 25° C. up to duration of 9 minutes after dilution and at 20° C. up to duration of 8 minutes after dilution.

Example 4

[0065]

TABLE-US-00005 Ingredients Amount (mg/ml) Percentage % Paracetamol 250 25% w/v Glycofurol 353 35.3% w/v Ethyl alcohol 240 24% w/v Plasdone C 17  40 4% w/v Water for Injection Qs to 1 ml Qs to 100%

[0066] The viscosity of the above formulation (undiluted) was 20.94 CPS when measured by Ostwald viscometer at 25° C.

[0067] When 4 ml (Volume equivalent to 1 gm) of the above formulation was diluted with water for injections up to a final volume of 20 ml, no recrystallization of drug was observed at 25° C. up to duration of 11 minutes after dilution and at 20° C. up to duration of 8 minutes after dilution

Example 5

[0068]

TABLE-US-00006 Ingredients Amount (mg/ml) Percentage % Paracetamol 250 25% w/v Glycofurol 353 35.3% w/v Ethyl alcohol 224 22.4% w/v Plasdone C 17 20 2% w/v N-Methyl Pyrollidone 20.6 2.06% w/v Water for Injection Qs to 1 ml Qs to 100%

[0069] The viscosity of the above formulation (undiluted) was 16.73 CPS when measured by Ostwald viscometer at 25° C.

[0070] When 4 ml (Volume equivalent to 1 gm) of the above formulation was diluted with water for injections up to a final volume of 20 ml, no recrystallization of drug was observed at 25° C. up to duration of 20 minutes after dilution.

Example 6

[0071]

TABLE-US-00007 Ingredients Amount (mg/ml) Percentage % Paracetamol 250   25% w/v Glycofurol 353 35.3% w/v Ethyl alcohol 160   16% w/v Plasdone C 17 20   2% w/v N-Methyl Pyrollidone 103 10.3% w/v Water for Injection Qs to 1 ml Qs to 100%

[0072] The viscosity of the above formulation (undiluted) was 16.46 CPS when measured by Ostwald viscometer at 25° C.

[0073] When 4 ml (Volume equivalent to 1 gm) of the above formulation was diluted with water for injections up to a final volume of 20 ml, no recrystallization of drug was observed at 25° C. up to duration of 20 minutes after dilution.

Example 7

[0074]

TABLE-US-00008 Ingredients Amount (mg/ml) Percentage % Paracetamol 250   25% w/v Glycofurol 353 35.3% w/v Ethyl alcohol 80   8% w/v Plasdone C 17 20   2% w/v N-Methyl Pyrollidone 206 20.6% w/v Water for Injection Qs to 1 ml Qs to 100%

[0075] The viscosity of the above formulation (undiluted) was 22.94 CPS when measured by Ostwald viscometer at 25° C.

[0076] When 4 ml (Volume equivalent to 1 gm) of the above formulation was diluted with water for injections up to a final volume of 20 ml, no recrystallization of drug was observed at 25° C. up to duration of 20 minutes after dilution.

Example 8

[0077]

TABLE-US-00009 Ingredients Amount (mg/ml) Percentage % Paracetamol 250 25% w/v Glycofurol 270 27% w/v Ethyl alcohol 240 24% w/v Plasdone C 17 20  2% w/v N-Methyl Pyrollidone 61.8 6.18% w/v   Water for Injection Qs to 1 ml Qs to 100%

[0078] The viscosity of the above formulation (undiluted) was 15.1 CPS when measured by Ostwald viscometer at 25° C.

[0079] When 4 ml (Volume equivalent to 1 gm) of the above formulation was diluted with water for injections up to a final volume of 20 ml, no recrystallization of drug was observed at 25° C. up to duration of 20 minutes after dilution.

Example 9

[0080]

TABLE-US-00010 Ingredients Amount (mg/ml) Percentage % Paracetamol 250 25% w/v Glycofurol 244.9 24.49% w/v   Ethyl alcohol 240 24% w/v Plasdone C 17 20  2% w/v N-Methyl Pyrollidone 103 10.3% w/v   Water for Injection Qs to 1 ml Qs to 100%

[0081] The viscosity of the above formulation (undiluted) was 11.76 CPS when measured by Ostwald viscometer at 25° C.

[0082] When 4 ml (Volume equivalent to 1 gm) of the above formulation was diluted with water for injections up to a final volume of 20 ml, no recrystallization of drug was observed at 25° C. up to duration of 20 minutes after dilution.

Example 10

[0083]

TABLE-US-00011 Ingredients Amount (mg/ml) Percentage % Paracetamol 250 25% w/v Glycofurol 270 27% w/v Ethyl alcohol 240 24% w/v N-Methyl Pyrollidone 61.8 6.18% w/v   Water for Injection Qs to 1 ml Qs to 100%

[0084] The viscosity of the above formulation (undiluted) was 13.2 CPS when measured by Ostwald viscometer at 25° C.

[0085] When 4 ml (Volume equivalent to 1 gm) of the above formulation was diluted with water for injections up to a final volume of 20 ml, no recrystallization of drug was observed at 25° C. up to duration of 8 minutes after dilution.

Example 11

[0086]

TABLE-US-00012 Ingredients Amount (mg/ml) Percentage % Paracetamol 250   25% w/v Glycofurol 353 35.3% w/v Plasdone C 17 20   2% w/v N-Methyl Pyrollidone 309 30.9% w/v Water for Injection Qs to 1 ml Qs to 100%

[0087] The viscosity of the above formulation (undiluted) was 30.22 CPS when measured by Ostwald viscometer at 25° C.

[0088] When 4 ml (Volume equivalent to 1 gm) of the above formulation was diluted with water for injections up to a final volume of 20 ml, no recrystallization of drug was observed at 25° C. up to duration of 20 minutes after dilution.

Example 12

[0089]

TABLE-US-00013 Ingredients Amount (mg/ml) Percentage % Paracetamol 250 25% w/v Ethyl alcohol 240 24% w/v Plasdone C 17 20  2% w/v N-Methyl Pyrollidone 257.5 25.75% w/v   Water for Injection Qs to 1 ml Qs to 100%

[0090] The viscosity of the above formulation (undiluted) was 8.41 CPS when measured by Ostwald viscometer at 25° C.

[0091] When 4 ml (Volume equivalent to 1 gm) of the above formulation was diluted with water for injections up to a final volume of 20 ml, no recrystallization of drug was observed at 25° C. up to duration of 20 minutes after dilution.

Example 13

[0092]

TABLE-US-00014 Ingredients Amount (mg/ml) Percentage % Paracetamol 250 25% w/v Ethyl alcohol 160 16% w/v N-Methyl Pyrollidone 439.6 43.96% w/v   Water for Injection Qs to 1 ml Qs to 100%

[0093] The viscosity of the above formulation (undiluted) was 9.29 CPS when measured by Ostwald viscometer at 25° C.

[0094] When 4 ml (Volume equivalent to 1 gm) of the above formulation was diluted with water for injections up to a final volume of 20 ml, no recrystallization of drug was observed at 25° C. up to duration of 20 minutes after dilution.

Example 14

[0095]

TABLE-US-00015 Ingredients Amount (mg/ml) Percentage % Paracetamol 250 25% w/v  Ethyl alcohol 80 8% w/v Plasdone C 17 20 2% w/v N-Methyl Pyrollidone 412 41.2% w/v   Water for Injection Qs to 1 ml Qs to 100%

[0096] The viscosity of the above formulation (undiluted) was 11.12 CPS when measured by Ostwald viscometer at 25° C.

[0097] When 4 ml (Volume equivalent to 1 gm) of the above formulation was diluted with water for injections up to a final volume of 20 ml, no recrystallization of drug was observed at 25° C. up to duration of 20 minutes after dilution.

Example 15

[0098]

TABLE-US-00016 Ingredients Amount (mg/ml) Percentage % Paracetamol 250   25% w/v Ethyl alcohol 80    8% w/v N-Methyl Pyrollidone 542.6 54.26% w/v Water for Injection Qs to 1 ml Qs to 100%

[0099] The viscosity of the above formulation (undiluted) was 10.61 CPS when measured by Ostwald viscometer at 25° C.

[0100] When 4 ml (Volume equivalent to 1 gm) of the above formulation was diluted with water for injections up to a final volume of 20 ml, no recrystallization of drug was observed at 25° C. up to duration of 20 minutes after dilution.

Example 16

[0101]

TABLE-US-00017 Ingredients Amount (mg/ml) Percentage % Paracetamol 250   25% w/v Plasdone C 17 20    2% w/v N-Methyl Pyrollidone 386.2 38.62% w/v Water for Injection Qs to 1 ml Qs to 100%

[0102] The viscosity of the above formulation (undiluted) was 10.24 CPS when measured by Ostwald viscometer at 25° C.

[0103] When 4 ml (Volume equivalent to 1 gm) of the above formulation was diluted with water for injections up to a final volume of 20 ml, no recrystallization of drug was observed at 25° C. up to duration of 20 minutes after dilution.

Example 17

[0104]

TABLE-US-00018 Ingredients Amount (mg/ml) Percentage % Paracetamol 250 25% w/v Glycofurol 150 15% w/v Ethyl alcohol 250 25% w/v Plasdone C 17 20  2% w/v N-Methyl Pyrollidone 248 24.8% w/v   Water for Injection Qs to 1 ml Qs to 100%

[0105] The viscosity of the above formulation (undiluted) was 12.6 CPS when measured by Ostwald viscometer at 25° C.

[0106] When 4 ml (Volume equivalent to 1 gm) of the above formulation was diluted with water for injections up to a final volume of 20 ml, no recrystallization of drug was observed at 25° C. up to duration of 20 minutes after dilution.

Example 18

[0107]

TABLE-US-00019 Ingredients Amount (mg/ml) Percentage % Paracetamol 250 25% w/v Glycofurol 200 20% w/v Ethyl alcohol 300 30% w/v Plasdone C 17 20  2% w/v N-Methyl Pyrollidone 156 15.6% w/v   Water for Injection Qs to 1 ml Qs to 100%

[0108] The viscosity of the above formulation (undiluted) was 14.5 CPS when measured by Ostwald viscometer at 25° C.

[0109] When 4 ml (Volume equivalent to 1 gm) of the above formulation was diluted with water for injections up to a final volume of 20 ml, no recrystallization of drug was observed at 25° C. up to duration of 20 minutes after dilution.

Example 19

[0110]

TABLE-US-00020 Ingredients Amount (mg/ml) Percentage % Paracetamol 250   25% w/v Glycofurol 353 35.3% w/v Ethyl alcohol 200   20% w/v Plasdone C 17 50   5% w/v N-Methyl Pyrollidone 32.5 3.25% w/v Water for Injection Qs to 1 ml Qs to 100%

[0111] The viscosity of the above formulation (undiluted) was 21.1 CPS when measured by Ostwald viscometer at 25° C.

[0112] When 4 ml (Volume equivalent to 1 gm) of the above formulation was diluted with water for injections up to a final volume of 20 ml, no recrystallization of drug was observed at 25° C. up to duration of 20 minutes after dilution.

Example 20

[0113]

TABLE-US-00021 Ingredients Amount (mg/ml) Percentage % Paracetamol 250 25% w/v Glycofurol 400 40% w/v Ethyl alcohol 90  9% w/v Plasdone C 17 20  2% w/v N-Methyl Pyrollidone 164 16.4% w/v   Water for Injection Qs to 1 ml Qs to 100%

[0114] The viscosity of the above formulation (undiluted) was 20.2 CPS when measured by Ostwald viscometer at 25° C.

[0115] When 4 ml (Volume equivalent to 1 gm) of the above formulation was diluted with water for injections up to a final volume of 20 ml, no recrystallization of drug was observed at 25° C. up to duration of 20 minutes after dilution.

[0116] The present invention has surprisingly found that Injectable formulations comprising 250 mg/ml paracetamol or its pharmaceutically acceptable salt, a solvent system comprising Glycofurol, Lower chain alcohol, a stabiliser, water which when diluted with aqueous fluids to not more than 20 ml remain stable. In another embodiment of the present formulation the other solvent component may be used. These formulations are also suitable for slow IV bolus administration with minimised side effects such as phlebitis.