Veterinary Composition

Abstract

The present invention relates to a veterinary composition for oral administration, said veterinary composition including an antacid and a therapeutically effective amount of a proton pump inhibitor, wherein the proton pump inhibitor is provided in an enteric coated form.

Claims

1. A veterinary composition for oral administration, said veterinary composition including an antacid and a therapeutically effective amount of a proton pump inhibitor, wherein the proton pump inhibitor is provided in an enteric coated form.

2. (canceled)

3. The veterinary composition according to claim 1, wherein the antacid is selected from one or more of the group consisting of: magnesium oxide, magnesium hydroxide, calcium carbonate, sodium bicarbonate, magnesium aluminate monohydrate, aluminium hydroxide, magnesium trisilicate, aluminium carbonate, magnesium carbonate, aluminium magnesium hydroxide sulfate and sodium citrate.

4. The veterinary composition according to claim 3, wherein the antacid includes magnesium oxide.

5. (canceled)

6. The veterinary composition according to claim 1, wherein the antacid is present in an amount of about 5% to about 25% by weight of the veterinary composition.

7. (canceled)

8. (canceled)

9. The veterinary composition according to claim 1, wherein the enteric coated form is present in an amount of about 5% to about 60% by weight of the veterinary composition.

10. (canceled)

11. (canceled)

12. (canceled)

13. (canceled)

14. (canceled)

15. (canceled)

16. (canceled)

17. (canceled)

18. The veterinary composition according to claim 1, wherein the proton pump inhibitor is selected from one or more of the group consisting of: omeprazole, lansoprazole, pantoprazole, rabeprazole and leminoprazole.

19. The veterinary composition according to claim 18, wherein the proton pump inhibitor includes omeprazole.

20. (canceled)

21. The veterinary composition according to claim 1, wherein the proton pump inhibitor is present in an amount of about 0.05% to about 55% by weight of the veterinary composition.

22. (canceled)

23. The veterinary composition according to claim 1, wherein the veterinary composition is in a paste dosage form.

24. The veterinary composition according to claim 1, wherein the veterinary composition includes a carrier selected from one or more of the group consisting of: mineral oil, avocado oil, castor oil, cottonseed oil, ethyl oleate, isopropyl myristate, isopropyl palmitate, myristyl alcohol, octyldodecanol, peanut oil, sunflower oil, capric triglycerides, caprylic triglycerides, safflower oil, sesame oil, canola oil, aniseed oil, macadamia nut oil, olive oil, squalene, rice bran oil, soya oil and almond oil.

25. (canceled)

26. The veterinary composition according to claim 24, wherein the carrier includes canola oil.

27. The veterinary composition according to claim 24, wherein the carrier is present in an amount of about 30% to about 85% by weight of the veterinary composition.

28. (canceled)

29. The veterinary composition according to claim 1, wherein the veterinary composition includes a thickening agent including silicon dioxide.

30. The veterinary composition according to claim 29, wherein the thickening agent is present in an amount of about 1% to about 15% by weight of the veterinary composition.

31. The veterinary composition according to claim 1, wherein the veterinary composition does not contain an added preservative.

32. A veterinary composition for oral administration, said veterinary composition including an antacid including magnesium oxide, a thickening agent, a carrier and a therapeutically effective amount of a proton pump inhibitor including omeprazole, wherein the proton pump inhibitor is provided in an enteric coated form and the enteric coated form, antacid and thickening agent are suspended or dissolved in the carrier.

33. The veterinary composition according to claim 32, wherein the veterinary composition is in a paste dosage form.

34. (canceled)

35. (canceled)

36. (canceled)

37. (canceled)

38. (canceled)

39. A method for the prevention or treatment of a gastric ulcer condition in an animal, including orally administering to said animal the veterinary composition according to claim 1.

40. The method according to claim 39, wherein the animal is a species selected from the group consisting of equine, porcine, bovine and canine.

41. The method according to claim 40, wherein the animal is a horse.

42. (canceled)

Description

BRIEF DESCRIPTION OF THE FIGURES

[0053] FIG. 1 is a plot of mean omeprazole plasma concentration as a function of time for treatments using a test composition of the present invention (IVP) and a registered reference product (RVP) in a two-period cross-over design study testing efficacy in horses.

DETAILED DESCRIPTION OF THE EMBODIMENTS

Example 1Formulation

[0054] A formulation of a veterinary composition of the present invention is exemplified in Table 1.

TABLE-US-00001 TABLE 1 Veterinary composition formulation. Formulation A B C D Ingredient wt % in composition Magnesium oxide light 15 13 13 13 Omeprazole pellets 21 31 37 39 (omeprazole) (4.2) (9.3) (3.1) (3.2) Canola oil 61 50 47 44 Silicon dioxide 3 6 3 3

[0055] Composition A is formulated as a 50 mg/mL omeprazole composition using omeprazole pellets containing about 20 wt % omeprazole by weight of the pellets. Composition B is formulated as a 100 mg/mL omeprazole composition using omeprazole pellets containing about 30 wt % omeprazole by weight of the pellets. Compositions C and D are formulated as 40 mg/mL omeprazole compositions using omeprazole pellets containing about 8.3 wt % omeprazole by weight of the pellets. The omeprazole pellet formulation includes omeparazole on a sugar core with a hydroxypropylmethylcellulose sealing layer (i.e. HPMC-E5) and a methacrylic acid copolymer (i.e. L-30D) enteric coat.

[0056] Each composition is beige in colour with visible white enteric coated pellets distributed throughout. Compositions are formulated in a paste dosage form intended for administration to horses and packaged in 36 mL dial-dose tubes. Optimal viscosity as determined by USP 39<912> is in the range of about 4000 to about 12000 cP. Optimal pH as determined by USP 38<791> is in the range of about 10 to about 12. Optimal total impurity levels are less than 2 wt % as determined by USP 38.

[0057] Composition A containing 20 wt % omeprazole pellets is characterised by comparatively better consistency for packaging and administration, and uniformity of content for consistent dosage administration.

Example 2Manufacture

[0058] A veterinary composition of Example 1 is manufactured by the following process. [0059] 1. Set up the Planetary Mixer with the Paddle Mixer attachment. [0060] 2. Place the mixing vessel into place on the Planetary Mixer and lock the bowl into position. Add the canola oil to the mixing vessel. [0061] 3. Set the timer for fifteen (15) minutes and start the mixer on slow speed (Speed 1) and slowly add the Magnesium Oxide over two portions stopping the mixer intermittently so that the side of the bowl can be scraped. [0062] 4. Set the mixer (speed 1) and mix for a further five (5) minutes to ensure the Magnesium Oxide is dispersed and no lumps are present. [0063] 5. Set the timer for ten (10) minutes and add the Silicon Dioxide whilst continuously mixing for five (5) minutes on slow speed (speed 1). Stop the mixer (and timer) at the five (5) minute mark and scrape down the side of the vessel. Continue mixing for the remaining five (5) minutes on medium (speed 2). Once the ten (10) minutes total mixing time is complete, scrape down the side of the mixing bowl with a teflon scraper. [0064] 6. Add the Omeprazole Pellets over two portions and mix with intermittent mixing between each addition. Set the timer and perform a final mix of ten (10) minutes on medium (Speed 2) so that the Omeprazole pellets are evenly dispersed through the product. [0065] 7. Stop the mixer and timer and scrape the excess material from the vessel and paddle into the bowl at the five (5) minute mark. Mix thoroughly using the Teflon scraper. [0066] 8. Remove the bowl from the Planetary Mixer and cover the bowl with a HDPE bag and leave overnight before filling is commenced.

Example 3Stability Trials

[0067] Stability trials were performed on one (1) 42 Kg batch and two (2) supporting 6 Kg batches of a composition corresponding to formulation A of Example 1 packaged in dial-dose tubes. Table 2 presents the results of stability trials at storage conditions of 302 C. and 655% Relative Humidity (% RH) tube tip facing downwards for 3 months. Appearance and pack integrity were assessed by visual inspection. Standard techniques and parameters were used to determine viscosity (i.e. USP 39<912>), pH (i.e. USP 39<791>) impurities (i.e. USP 38) and assay.

TABLE-US-00002 TABLE 2 Storage 30 2 C. and 65 5% Relative Humidity (% RH) tube tip facing downwards. Total Batch impurities Assay No. Appearance Pack integrity Viscosity cP pH wt % mg/ml 1 Beige colour, white Intact; no colour 4900 11.0 0.45 51.8 pellets evenly distributed; variation; no leaks no evidence of separation 2 Beige colour, white Intact; no colour 5300 10.6 0.57 49.8 pellets evenly distributed; variation; no leaks no evidence of separation 3 Beige colour, white Intact; no colour 8400 10.0 0.42 48.9 pellets evenly distributed; variation; no leaks no evidence of separation

[0068] Stability trials were also performed on a 50 Kg batch of a composition corresponding to formulation D of Example 1. Table 3 presents the results of accelerated stability trials at storage conditions of 402 C. and 755% Relative Humidity (% RH) inverted. Appearance was assessed by cutting the tube lengthways and without mixing visually assessing the colour and homogeneity of the composition. Pack integrity was assessed by visual assessment. SG, assay and micro data was determined using standard techniques and parameters. The micro data in particular demonstrates that it is not necessary to include an added preservative in a veterinary composition of the present invention.

TABLE-US-00003 TABLE 3 Storage 40 2 C. and 75 5% Relative Humidity (% RH) inverted. Micro Time Assay mg/ml, Bacteria Yeast/mould point Appearance Pack integrity SG % w/w (in pellets) (cfug) (cfug) E. coli 0 Beige colour, white Intact; no colour 1.23 41.5, 8.0 <10.sup.3 <10.sup.2 Absent pellets evenly distributed; variation; no leaks no evidence of separation +1 Beige colour, white Intact; no colour 1.24 40.9, 8.2 <10.sup.2 <10.sup.2 Absent month pellets evenly distributed; variation; no leaks no evidence of separation +2 Beige colour, white Intact; no colour 1.22 41.4, 8.9 <10.sup.2 <10.sup.2 Absent months pellets evenly distributed; variation; no leaks no evidence of separation +4 Beige colour, white Intact; no colour 1.21 36.5, 8.2 <10.sup.2 <10.sup.2 Absent months pellets evenly distributed; variation; no leaks no evidence of separation

Example 4Experimental Trials

[0069] A sample population of 30 horses was treated with composition C or D of Example 1. Each horse was administered with a 5 mL dosage amount once daily for a period of at least 2 weeks or while in work or training. Symptoms of a gastric ulcer condition were absent from most to all horses after this treatment period. Veterinarian and Trainer feedback also included that horses treated with a veterinary composition of the present invention were characterised by the following: [0070] Improved appetite; [0071] Improved temperament; [0072] Improved work/training performance; [0073] Increased coat shine; [0074] Decreased incidence of product rejection upon administration; [0075] Increased willingness to receive treatment.

[0076] Reduced administration frequency was also reported in comparison with experiences with other products. For example, Veterinarians and Trainers noted that other products often require two to three administrations per day at higher dosage amounts for any observable effects, while a single administration of a veterinary composition of the present invention was sufficient in many cases for fast and effective treatment.

Example 5Efficacy Studies

[0077] A two-period cross-over design was used to test the efficacy in horses of a test composition of the present invention (IVP) compared with a market-leading registered reference product, marketed under the trade name Gastrozol (RVP). 28 horses were randomly separated into two even groups. Horses in one group received a single dose of the RVP in a first period and after a washout period then received a single dose of the IVP in a second period. Horses in the other group received a single dose of the IVP in a first period and after a washout period then received a single dose of the RVP in a second period. All dosage amounts were 5 mL.

[0078] The IVP was a composition A of Example 1 in paste dosage form delivering about 250 mg of omeprazole per 5 mL dose. The RVP was also in paste dosage form nominally formulated as a 50 mg/mL omeprazole composition delivering 250 mg omeprazole per 5 mL dose. The reverse-engineered formulation of the RVP is provided in Table 3.

TABLE-US-00004 TABLE 3 RVP formulation. Ingredient approx. wt % in composition Omeprazole beads 31.3 Paraffin oil 68.3 Diethyl phthalate; vanillin; 0.4 glycerol; parabens

[0079] Plasma samples were taken from horses at a number of time intervals following dosage administration and analysed for omeprazole concentration. Data were assessed for pharmacokinetics parameters AUC, C.sub.max and T.sub.max. A plot of mean omeprazole plasma concentration as a function of time for IVP and RVP treatments is provided in FIG. 1.

[0080] Values for the measured pharmacokinetic parameters are provided in Table 4.

TABLE-US-00005 TABLE 4 Measured mean pharmacokinetic parameters. AUC (g/L .Math. hr) C.sub.max(g/L) T.sub.max(hr) RVP 1474.28 623.400 1.31 IVP 1922.31 886.884 1.17 IVP RVP 448.03 263.484 0.14

[0081] The IVP achieved a statistically significant higher AUC compared to the RVP and a statistically significant higher C.sub.max in less time (i.e. T.sub.max).

[0082] It is to be understood that various alterations, modifications and/or additions may be made without departing from the spirit of the present invention as outlined herein.

[0083] As used herein, except where the context requires otherwise, the term comprise and variations of the term, such as comprising, comprises and comprised, are not intended to be in any way limiting or to exclude further additives, components, integers or steps.

[0084] Reference to any prior art in the specification is not, and should not be taken as, an acknowledgment or any form of suggestion that this prior art forms part of the common general knowledge in Australia or any other jurisdiction or that this prior art could reasonably be expected to be ascertained, understood and/or regarded as relevant by a person skilled in the art.