TABLETS WITH IMPROVED FRIABILITY

Abstract

Tablets are prepared with friability reducing agents to yield tablets that are more resistant to breakage or crumbling, but with satisfactory hardness. The friability reducing agents include low molecular weight polyethylene glycol as well as similar agents exhibiting at least three percent (3%) hydroxide moieties and a water solubility of at least eighty percent (80%) (w/w %) in room temperature water. The tablets may comprise an active agent and excipient of almost any type, and about 0.1-about 0.5% by weight friability reducing agent. They exhibit a hardness of at least eighty percent (80%) of the same tablet prepared without the friability reducing agent.

Claims

1-10. (canceled)

11. A tablet exhibiting reduced friability, said tablet comprising: A) An active agent which is a nutritional product; B) an excipient compatible with said active agent; and C) an agent to reduce tablet friability present in amounts of about 0.1%-about 5.0% by weight of the tablet, wherein said friability reducing agent exhibits a solubility in room temperature water of at least eighty percent (80%) (w/w %), wherein said friability reducing agent is comprised of at least three percent (3%) by weight —OH moieties and wherein said tablet comprising said friability reducing agent exhibits a hardness of at least eighty percent (80%) of the hardness exhibited by said tablet prepared in the absence of said friability.

12. The tablet of claim 11, wherein said tablet comprises a medication.

13. The tablet of claim 11, wherein said tablet comprises an effervescent couple which combine to effervesce when moistened.

14. The tablet of claim 11 wherein said tablet is at least ¾ inch in diameter.

15. The tablet of claim 12, wherein said medication is a pharmaceutical preparation available with a prescription or an over-the-counter product.

16. The tablet of claim 11, wherein said friability reducing agent is present in amounts of about 0.1-about 1.0% by weight.

17. The tablet of claim 11, wherein said excipient is a stabilizer, lubricant, a binder, a disintegrant, or a coating.

18. The tablet of claim 11, wherein said friability reducing agent is present in amounts of about 0.1%-about 0.6% by weight.

19. The tablet of claim 11, wherein said tablet is intended for consumption by an animal.

20. The tablet of claim 19, wherein said animal is a mammal.

21. The tablet of claim 20, wherein said mammal is a human.

Description

SPECIFIC EXAMPLES OF THE INVENTION

[0017] The following examples demonstrate this performance. The examples are provided for purposes of demonstration only, and are not intended to limit the invention in any way. Other active agents and excipients, as well as other agents effective in reducing friability, within the broad parameters set forth above, will occur to those of skill in the art.

Example 1: Denture Cleanser Tablet

[0018] The following base denture cleanser formula was prepared by blending the indicated ingredients (Table 1) using conventional powder mixing equipment.

TABLE-US-00001 TABLE 1 Material % w/w Sodium Bicarbonate 25.0 Citric Acid 20.0 Sodium Carbonate 15.0 Potassium Monopersulfate 10.0 Sodium Perborate Monohydrate 10.0 Maltodextrin 9.5 Sodium Sulfate 8.7 Sodium Lauryl Sulfoacetate 0.7 PEG 8000 0.7 Flavor Oil 0.3 Sodium Benzoate 0.1 Total 100.0

[0019] Formulations that demonstrate the invention were prepared by adding the indicated amount of PEG 400. The formulas were balanced to one hundred percent (100%) by reducing the amount of sodium sulfate.

[0020] Tablets were compressed using ⅞″ round tooling on a Stokes F press. Compression force was adjusted to give the hardest possible tablet (limit set by capability of the press or by the appearance of tablet capping). Data is shown in Table 2.

[0021] Hardness was measured using a Schuleuniger-4M tablet hardness tester.

[0022] Friability was measured in a manner similar to that described in the USP-NF, Chapter <1216>. The USP-NF method was modified in that the number of tablet used and the method of calculation were changed as indicated here. Ten (10) tablets were placed in an Erweka TA friability apparatus. The tablets were tumbled at 25 rpm for the indicated number of minutes. The percentage of unbroken tablets is reported.

[0023] Dissolution time was measured by placing a tablet in 125 ml of water at 25° C. The time needed for essentially complete dissolution is reported.

TABLE-US-00002 TABLE 2 Friability (% whole tablets) PEG 400 Weight Hardness Thickness 2 4 6 8 10 Dissolution concentration (g) (kp) (mm) min min min min min Time (sec)   0% 2.69 7.8 3.96 70 10 0 0 0 83 0.1% 2.70 8.2 3.95 100 85 40 15 5 82 0.6% 2.69 9.0 3.82 100 100 100 100 100 103 1.0% 2.65 8.5 3.85 100 100 100 100 100 145 5.0% 2.80 4.6 4.21 100 100 100 100 100 71

[0024] This data clearly shows the effect of PEG 400 on the denture cleanser composition. Below five percent (5%) PEG 400, friability is unexpectedly and dramatically improved while hardness and dissolution time are not significantly affected. At five percent (5%) though, the tablet's hardness is decreased to an unacceptable level.

Example 2: Alternate Molecular Weight PEGs

[0025] The effect of different molecular weight PEGs was investigated. The PEGs listed in Table 3 were evaluated using the formula shown in Table 1. 0.6% PEG was used in each trial. The formulas were balanced to 100% by reducing sodium sulfate. Data is shown below.

TABLE-US-00003 TABLE 3 Friability (% Whole Tablets) Weight Hardness Thickness 2 4 6 8 10 Dissolution PEG MW (g) (kp) (mm) min min min min min Time (sec) None (control) 2.69 7.8 3.96 70 10 0 0 0 83 200 2.66 8.1 3.92 100 100 100 100 100 72 400 2.69 9.0 3.82 100 100 100 100 100 103 600 2.69 7.5 3.94 100 100 100 100 100 145 1000 2.71 7.4 3.98 100 85 30 0 0 82 1450 2.62 6.6 3.90 60 20 5 0 0 73

[0026] Clearly, the friability benefit of the invention is maximized when using PEGs with MW between 200 and 1,000. The drop in performance at MW 1450 is surprising.

Example 3: Alternate Materials Similar in Structure to PEG

[0027] Materials with chemical structures somewhat similar to PEG were tested to assess their performance in reducing tablet friability. That is, we assessed hydrophilic materials that are ethoxylated or propoxylated. A range of chain length materials were investigated. For comparison purposes, we also looked at a hydrophobic material (mineral oil) and glycerin (as a very short chain, high hydroxyl content material). These assessments were conducted using the denture cleanser formulation shown in Table 1.

[0028] Data from these experiments are presented in Table 4:

TABLE-US-00004 TABLE 4 Friability (% Whole Tablets) Material added Weight Hardness 2 4 6 8 10 (0.6% formula) Structure (g) (kp) min min min min min No additive — 2.69 7.8 70 10 0 0 0 PEG 400 H—(O—CH.sub.2—CH.sub.2).sub.8—OH 2.69 9.0 100 100 100 100 100 Polypropylene glycol H—(O—CH(CH.sub.3)CH.sub.2).sub.4—OH 2.64 8.0 100 100 100 100 100 250 (PPG-4) Polypropylene glycol H—(O—CH(CH.sub.3)—CH.sub.2).sub.9—OH 2.67 7.5 100 80 55 30 0 425 (PPG-9) Polypropylene glycol H—(O—CH(CH.sub.3)—CH.sub.2).sub.10—OH 2.65 6.5 100 70 30 10 0 700 (PPG-10) Polypropylene glycol H—(O—CH(CH.sub.3)—CH.sub.2).sub.26—OH 2.67 3.7 20 0 0 0 0 2000 (PPG-26) Methoxypolyethylene CH.sub.3—(O—CH.sub.2—CH.sub.2).sub.6—OH 2.66 6.4 100 100 100 100 100 glycol 350 (MPEG-6) Methoxypolyethylene CH.sub.3—(O—CH.sub.2—CH.sub.2).sub.10—OH 2.66 6.4 100 100 100 100 100 glycol 550 (MPEG-10) Tween 80 (Polysorbate 80) [00001] 2.69 5.6 100 100 90 95 85 Mineral Oil C.sub.nH.sub.2n+2 n=12−40 2.65 7.4 90 60 30 0 0 Glycerin OH—CH.sub.2—C(OH)—CH.sub.2—OH 2.65 9.5 100 100 100 100 100 [00002]

[0029] In an attempt to understand what chemical properties of the tested materials are critical to improving friability, we looked at some of the physical properties of the tested materials. Table 5 provides these comparisons:

TABLE-US-00005 TABLE 5 Friability Appearance at Room Material improvement Solubility in Water (w/w %) Temperature PEG 200 Yes 100% Clear viscous liquid PEG 400 Yes 100% Clear viscous liquid PEG 600 Yes 100% Clear viscous liquid PEG 1000 Somewhat  80% Soft, Opaque white solid PEG 1450 No  72% Soft, Opaque white solid MPEG 350 Yes 100% Clear viscous liquid MPEG 550 Yes 100% Clear viscous liquid PPG 250 Yes 100% Clear viscous liquid PPG 425 Yes Soluble at room temperature, but Clear viscous liquid insoluble at higher temperatures PPG 700 Somewhat Soluble to slightly soluble at Clear viscous liquid room temperature PPG 2000 No   0% Clear viscous liquid Tween 80 Yes 100% Clear viscous liquid (yellow) Mineral Oil No   0% Clear viscous liquid Glycerin Yes 100% Clear viscous liquid

[0030] Examining these data, it appears that agents which are at least somewhat soluble in water at room temperature exhibit the inventive effect. It will be evident that the friability reducing agents of this invention are physically and chemically compatible with each other. Accordingly, they may be used in combination and in mixtures. Given the desirability of limiting the amount of the friability reducing agent present in the tablet in general, the Examples herein focus on one agent or another, but multiple agents could be used together, provided the weight limits are observed, and any reduction in hardness is controlled

Example 4: Acids Other than Citric Acid

[0031] Denture cleanser tablets formulated according to Table 1, with PEG 400 at included at the indicated level were produced with acids other than citric acid. This was done to ascertain if the inventive effect is limited to products based only on citric acid. Table 6 displays the results of this experiment:

TABLE-US-00006 TABLE 6 PEG 400 Weight Hardness Friability (% Whole Tablets) Acid level (%) (g) (kp) 2 min 4 min 6 min 8 min 10 min Citric Acid 0 2.69 7.77 70 10 0 0 0 Citric Acid 0.6 2.69 8.96 100 100 100 100 100 Fumaric Acid 0 2.61 5.09 25 0 0 0 0 Fumaric Acid 0.6 2.60 5.80 100 100 95 90 85 Malic Acid 0 n/a n/a — — — — — Malic Acid 0.6 2.39 5.28 100 100 100 100 100 Sodium Bisulfate 0 2.66 6.56 10 0 0 0 0 Sodium Bisulfate 0.6 2.70 5.99 85 40 10 0 0

[0032] The above data clearly show the benefits of including PEG 400 in the formulation. Most notably, and surprisingly, tablets made with malic acid could not be produced without inclusion of the low molecular weight PEG.

[0033] Product formulations other than denture tablets were also studied. Examples follow.

Example 5: Vitamin C Drink Tablet

[0034] An effervescent Vitamin C tablet (designed to dissolve in water before ingesting) was developed using the composition shown in Table 7. The formula was prepared by blending the indicated ingredients using conventional powder mixing equipment.

TABLE-US-00007 TABLE 7 Material % w/w Ascorbic Acid 33.4 Citric Acid 33.4 Sodium Bicarbonate 8.3 Potassium Bicarbonate 8.3 Sorbitol 8.6 Maltodextrin 2.0 Flavor Oil 0.2 Sucralose 0.4 PEG 8000 4.4 Sodium Benzoate 1.0 Total 100.0

[0035] Formulations that demonstrate the invention were prepared by adding the indicated amount of PEG 400. The formulas were balanced to one hundred percent (100%) by reducing the amount of sorbitol.

[0036] Three (3) gram tablets were compressed using ⅞″ round tooling on a Stokes F press. Compression force was adjusted to give the hardest possible tablet (limit set by capability of the press or by appearance of tablet capping).

[0037] These tablets were evaluated by the same methods discussed above. Data are shown in Table 8.

TABLE-US-00008 TABLE 8 Friability (% Whole Tablets) PEG 400 Weight Hardness Thickness 2 4 6 8 10 concentration (g) (kp) (mm) min min min min min Comments 0 2.95 5.4 5.03 50 0 0 0 0 — 0.1% 2.99 6.1 5.06 100 95 60 25 5 — 0.6% 2.92 6.7 4.92 100 100 100 100 100 — 1.0% 2.78 3.7 5.05 100 100 100 100 100 — 5.0% — — — — — — — — Tablets could not be pressed due to punch face sticking and sidewall scoring

[0038] Again, the addition of a small amount of PEG 400 provides the unexpected result of highly improved friability without harm to other properties.

Example 6: Beverage Tablet

[0039] An effervescent tablet designed to form a lemon/lime beverage when dissolved in water was formulated as shown in Table 9:

TABLE-US-00009 TABLE 9 Material % w/w Citric Acid 54.6 Sodium Bicarbonate 21.2 Sorbitol 17.7 Lemon/Lime Flavor Oil 0.9 Acesulfame K 0.4 Aspartame 1.0 PEG 8000 2.7 Sodium Benzoate 1.5 Total 100.0

[0040] Formulations that demonstrate the invention were prepared by adding the indicated amount of PEG 400. The formulas were balanced to one hundred percent (100%) by reducing the amount of sorbitol.

[0041] 3.3 gram tablets were compressed using ⅞″ round tooling on a Stokes F press. As above, compression force was adjusted to give the hardest possible tablet (limit set by capability of the press or by appearance of tablet capping).

[0042] These tablets were evaluated by the same methods discussed above. Data are shown in Table 10.

TABLE-US-00010 TABLE 10 PEG 400 Hard- Thick- Friability (% Whole Tablets) concen- Weight ness ness 2 4 6 8 10 tration (g) (kp) (mm) min min min min min 0 3.27 7.1 5.60 100 75 35 0 0 0.6% 3.27 7.7 5.55 100 100 100 100 100

[0043] Again, the dramatic effect of low molecular weight PEG addition was demonstrated.

[0044] It may be noted that all of the formulations in the above examples are effervescent. That is, they contain one or more organic acids and one or more carbonate salts. In the presence of water the acid and the carbonate salt react to release carbon dioxide, creating a bubbling action that is appealing to consumers and that disperses formula ingredients. Many examples of effervescent products (developed for many reasons) can be found in the art. Given that effervescent formulations are somewhat specialized, our inventive technology was also checked in a non-effervescent formulation.

Example 7: Candy Tablet

[0045] A tart, sugar based candy tablet was developed according to the formula shown in Table 11. This tablet can be dissolved in the mouth as a lozenge.

TABLE-US-00011 TABLE 11 Material % w/w Dextrose 44.7 Maltodextrin 44.4 Citric Acid 10.0 Lemon/Lime Flavor Oil 0.3 PEG 8000 0.5 Sodium Benzoate 0.1 Total 100.0

[0046] Formulations that demonstrate the invention were prepared by adding the indicated amount of PEG 400. The formulas were balanced to one hundred percent (100%) by reducing the amount of maltodextrin.

[0047] 2.5 gram tablets were compressed using ⅞″ round tooling on a Stokes F press. As above, compression force was adjusted to give the hardest possible tablet (limit set by capability of the press or by appearance of tablet capping).

[0048] These tablets were evaluated by the same methods discussed above. Data are shown in Table 12.

TABLE-US-00012 TABLE 12 Friability (% Whole Tablets) PEG 400 Weight Hardness Thickness 2 4 6 8 10 Comments concentration (g) (kp) (mm) min min min min min 0 2.38 5.8 4.66 40 0 0 0 0 — 0.1% 2.37 4.7 4.58 70 35 5 0 0 — 0.6% 2.40 6.0 4.61 100 100 100 85 75 — 1.0% — — — — — — — — Flow issues. Tablets were not pressed

[0049] These data clearly demonstrate the benefits of the invention in a non-effervescent formulation.

[0050] While the present invention has been disclosed with references to certain embodiments, numerous modification, alterations, and changes to the described embodiments are possible without departing from the sphere and scope of the present invention, as defined in the appended claims. Accordingly, it is intended that the present invention not be limited to the described embodiments, but that it has the full scope defined by the language of the following claims, and equivalents thereof.