Pantoprazole multiparticulate formulations
View Patent ↗Pantoprazole sodium multiparticulates are described which avoid sticking to nasogastric and gastronomy tubes. The pantoprazole multiparticulates have a spheroid core of pantoprazole or an enantiomer thereof, or a salt thereof, a surfactant, and a distintegrant; a sub coat which is comprised of hydroxypropyl methylcellulose (hypromellose) and water, an enteric coat on the sub-coat, and a final seal coat over the enteric coat, which is composed of hydroxypropyl methylcellulose (hypromellose) and water.
1. A method of producing a multiparticulate formulation of pantoprazole having reduced release under gastric conditions and fast release at neutral pH, said method comprising the steps of:
producing a spheroid core comprising about 45% w/w pantoprazole sodium sesquihydrate, as a sole active component in the multiparticulate formulation and about 25% to 30% w/w microcrystalline cellulose, about 4% to 6% w/w polysorbate 80, about 14% to 16% w/w crospovidone, about 0.5 to 2% w/w hydroxypropyl methylcellulose, and about 5% to 8% w/w sodium carbonate a surfactant via extrusion and spheronization, said core further containing about 1 to about 2% w/w water;
applying an initial seal coat comprising hydroxypropyl methylcellulose to the spheroid core,
applying an enteric coating to the initial seal coated spheroid core, said enteric coating comprising a copolymer of methacrylic acid and methacrylates;
and optionally applying a final seal coat to the enteric-coated spheroid core, said final seal coat being about 1 wt % of the multiparticulate;
wherein the multiparticulates have an average diameter of about 0.7 mm to about 1.25 mm.
2. The method according to claim 1 , wherein the spheroid core is prepared by mixing the ingredients in a low shear mixer at low shear conditions at a range of about 25 rpm to 35 rpm.
3. The method according to claim 2 , wherein the low shear conditions are 32 rpm.
4. The method according to claim 2 , wherein the spheroid cores are dried at a low temperature not exceeding about 40° C. for a period of 8 to 72 hours to a percent (%) loss-on-drying (LOD) of 3.4% to 4.3%.
5. The method according to claim 1 , further comprising the step of applying a layer of talc in an amount of 0.05% w/w to 0.1% w/w of the multiparticulates.
6. The method according to claim 1 , wherein the enteric coating is sprayed as a suspension onto the spheroid core.
7. Pantoprazole multiparticulates having reduced release under gastric conditions and fast release at neutral pH, wherein each of said multiparticulates comprises: a spheroid core comprising about 45% w/w pantoprazole sodium sesquihydrate as a sole active component in the multiparticulates about 25% to 30% w/w microcrystalline cellulose, about 4% to 6% w/w polysorbate 80, about 14% to 16% w/w crospovidone, about 0.5 to 2% w/w hydroxypropyl methylcellulose, about 5% to 8% w/w sodium carbonate, and about 1 to 2% w/w water; an initial seal coat comprising hydroxypropyl methylcellulose on the spheroid core; and an enteric coat on the initial seal coat, wherein said multiparticulates have an average diameter of about 0.7 mm to about 1.25 mm.
8. The multiparticulates according to claim 7 , wherein said multiparticulates have an average diameter of about 1 mm.
9. The multiparticulates according to claim 7 , wherein said enteric coat comprises about 48% w/w of the particulate,
10. The multiparticulates according to claim 7 , further comprising a final seal coat on the enteric coat.
11. The multiparticulates according to claim 10 , wherein the final seal coat comprises about 0.1 to 10 wt % of the multiparticulates.
12. The multiparticulates according to claim 10 , wherein the final seal coat comprises hydroxypropyl methylcellulose (hypromellose).
13. The multiparticulates according to claim 7 wherein said initial seal coat is in the range of about 2 to about 4% w/w of the weight of the uncoated core.
14. The multiparticulates according to claim 7 , wherein the enteric coating comprises about 30% w/w of methacrylic acid and methyacrylate copolymer, about 15% w/w talc, about 3% triethyl citrate and a pH adjuster; said amounts being by weight of the multiparticulates.
15. A pantoprazole formulation comprising a suspension comprising the multiparticulates of claim 7 and a physiologically compatible suspending liquid.
16. A capsule comprising the multiparticulates of claim 7 .
17. A foil packet comprising the multiparticulates according to claim 7 .
18. The method according to claim 1 , wherein the spheroid core consists essentially of:
pantoprazole sodium sesquihydrate
about 45%
w/w
microcrystalline cellulose
about 27%
w/w
polysorbate 80
about 5%
w/w
crospovidone
about 15%
w/w
hydroxypropylmethylcellulose
about 1%
w/w
sodium carbonate
about 6.5%
w/w: and
water.
19. The pantoprazole multiparticulates according to claim 7 , wherein the spheroid core consists essentially of:
pantoprazole sodium sesquihydrate
about 45%
w/w
microcrystalline cellulose
about 27%
w/w
polysorbate 80
about 5%
w/w
crospovidone
about 15%
w/w
hydroxypropylmethylcellulose
about 1%
w/w
sodium carbonate
about 6.5%
w/w: and
water.
20. A plurality of pantoprazole multiparticulates, each comprising: a spheroid core consisting essentially of about 45% w/w pantoprazole sodium sesquihydrate, about 27% w/w microcrystalline cellulose, about 5% w/w polysorbate 80; about 15% w/w crospovidone; about 1% w/w hydroxypropy methylcellulose, about 6.5% w/w sodium carbonate; and water; an inner seal coat comprising hydroxypropyl methylcellulose; and an enteric coating comprising a methacrylic acid and meth[yl]acrylate polymer, and triethylcitrate, wherein multiparticulates have an average diameter in the range of about 0.7 mm to about 1.25 mm.
21. The product according to claim 20 , wherein the enteric coating further comprises talc.
22. The product according to claim 21 , wherein the enteric coating further comprises sodium hydroxide.