Fast onset orodispersable tablets
The present invention provides orodispersable tablets and methods of using the same. The tablets and methods are useful, for example, for reducing first pass metabolism of orally administered active agents, enhancing bioavailability of active agents, and/or reducing the time it takes for an active agent to achieve maximal effect in a subject. The tablets, when taken orally, disintegrate or dissolve rapidly such that active agent included in the tablets is absorbed in the buccal cavity. The invention further provides methods of manufacturing any of the tablets disclosed herein and containers that include any of the tablets disclosed herein.
1. An orodispersable tablet comprising:
an active agent;
a binder comprising a polymer which is hydroxypropylcellulose or hydroxypropylmethylcellulose having a lower critical solution temperature (LCST) greater than 40° C.; and
a modifier,
wherein the ratio of modifier to said polymer is 30:1 to 2:1;
wherein said modifier reduces the LCST of said polymer to 37° C. or less; and
wherein in the absence of a disintegrant the tablet disintegrates in less than 60 seconds when administered orally.
2. The tablet of claim 1 , wherein said modifier is an electrolyte, and wherein said electrolyte comprises a cation selected from the group consisting of calcium, magnesium, potassium, sodium, or a combination thereof.
3. The tablet of claim 1 , wherein said modifier is an electrolyte, and wherein said electrolyte comprises an anion selected from the group consisting of citrate, phosphate, sulfate, or a combination thereof.
4. The tablet of claim 1 , wherein the modifier is an electrolyte selected from the group consisting of calcium sulfate, magnesium sulfate, potassium phosphate, and sodium citrate.
5. The tablet of claim 1 , wherein the modifier is a polyol selected from the group consisting of mannitol and xylitol.
6. The tablet of claim 1 , wherein the modifier comprises an electrolyte selected from the group consisting of calcium sulfate, magnesium sulfate, potassium phosphate, and sodium citrate, and a polyol selected from the group consisting of mannitol and xylitol.
7. The tablet of claim 1 , wherein the active agent is substantially insoluble in water.
8. The tablet of claim 1 , wherein the active agent is a therapeutic agent selected from the group consisting of amphentamine/dextroamphentamine, dextromethorphan, donepezil HCl, ergotamine tartrate, fentanyl, fentanyl citrate, granisetron HCl, methylphenidate HCl, ondansetron, ramosetron HCl, risperidone, sufentanil, sufentanil citrate, sumatriptan succinate, zaleplon, zolpidem tartrate, and zopiclone.
9. The tablet of claim 1 , wherein the active agent is risperidone.
10. The tablet of claim 1 , wherein said tablet has a friability less than 2%.
11. The tablet of claim 1 , further comprising a carrier for the active agent, wherein the carrier comprises porous particles, a solubility enhancing agent, a taste-masking agent, a temperature responsive agent, or a combination thereof.
12. The tablet of claim 1 , further comprising a lubricant, a taste-masking agent, a bulking agent, or any combination thereof.
13. A method for manufacturing a tablet of claim 1 , comprising:
granulating said polymer and said modifier to produce a granulated mass;
compressing said granulated mass to produce a tablet; and
optionally, color coating said tablet.
14. The method of claim 13 , wherein said granulating comprises wet granulation, fluid-bed granulation, roller-compaction granulation, or a mixture thereof.
15. A container comprising a tablet of claim 1 and an instruction, wherein said instruction provides:
the tablet is to be taken orally; and
the tablet disintegrates upon contact with saliva in less than 60 seconds.
16. The container of claim 15 , wherein said instruction further provides that active agent is absorbed in the buccal cavity, the tablet reduces first pass metabolism of the active agent, the tablet enhances bioavailability of said active agent, the tablet reduces the time it takes for the active agent to achieve maximal effect, or any combination thereof.
17. A method of administering an active agent to a subject, the method comprising providing a tablet of claim 1 to said subject with instructions to take the tablet orally, wherein said tablet comprises said active agent.
18. The method of claim 17 , wherein taking said tablet orally reduces first pass metabolism of said active agent in said subject, enhances bioavailability of said active agent in said subject, or reduces the time for said active agent to achieve maximal effect in said subject.
19. The method of claim 17 , wherein taking said tablet orally results in absorption of said active agent in the buccal cavity of said subject.
20. The method of claim 17 , wherein taking said tablet orally results in absorption of at least 50% of said active agent in said tablet in the buccal cavity of said subject.