FORMULATIONS OF RIFAXIMIN AND USES THEREOF
The present invention relates to new rifaximin forms comprising solid dispersions of rifaximin, methods of making same and to their use in medicinal preparations and therapeutic methods.
1 . A form solid dispersion of rifaximin.
2 . The form according to claim 1 , wherein the form solid dispersion of rifaximin is characterized by an XRPD substantially similar to one or more of the XRPDs of FIGS. 2 , 7 , 12 , 17 , 22 , 31 , and 36 .
3 . The form according to claim 1 , wherein the form solid dispersion of rifaximin is characterized by a Thermogram substantially similar to FIGS. 3-6 , 8 - 11 , 13 - 16 , 18 - 21 , 23 - 26 , 27 - 30 , and 32 .
4 . The form according to of claim 1 , wherein the form has the appearance of a single glass transition temperature (Tg).
5 . The form according to of claim 1 , wherein a Tg of a form increases with an increased rifaximin concentration
6 . The form according to of claim 1 , wherein a form stressed at 70° C./75% RH for 1 week, solids are still x-ray amorphous according to XRPD.
7 . The form according to of claim 1 , wherein a form stressed at 70° C./75% RH for 3 weeks, solids are still x-ray amorphous according to XRPD.
8 . The form according to of claim 1 , wherein a form stressed at 70° C./75% RH for 6 weeks, solids are still x-ray amorphous according to XRPD.
9 . The form according to of claim 1 , wherein a form stressed at 70° C./75% RH for 12 weeks, solids are still x-ray amorphous according to XRPD.
10 . A microgranule comprising the solid dispersion form of rifaximin as described in claim 1 .
11 . The microgranule of claim 10 , further comprising a polymer.
12 . The microgranule of claim 11 , wherein the polymer comprises one or more of polyvinylpyrrolidone (PVP) grade K-90, hydroxypropyl methylcellulose phthalate (HPMC-P) grade 55, hydroxypropyl methylcellulose acetate succinate (HPMC-AS) grades HG and MG, or a polymethacrylate (Eudragit® L100-55).
13 . The microgranule of claim 12 , wherein the microgranule comprises 25-75% polymer.
14 . The microgranule of claim 13 , wherein the microgranule comprises 40-60% polymer.
15 . The microgranule of claim 14 , wherein the microgranule comprises 40-50% polymer.
16 . The microgranule of claim 15 , wherein the microgranule comprises 42-44% polymer.
17 . The microgranule of claim 11 , wherein the microgranule comprises equal amounts of rifaximin and polymer.
18 . The microgranule of claim 10 , further comprising an intragranular release controlling agent.
19 . The microgranule of claim 18 , wherein the intragranular release controlling agent comprises between about 2 wt % to about 40 wt % of the microgranule.
20 . The microgranule of claim 19 , wherein the intragranular release controlling agent comprises between about 5 wt % to about 20 wt % of the microgranule.
21 . The microgranule of claim 20 , wherein the intragranular release controlling agent comprises about 10 wt % of the formulation.
22 . The microgranule of claim 18 , wherein the intragranular release controlling agent comprises a pharmaceutically acceptable excepient.
23 . The microgranule of claim 22 , wherein the intragranular release controlling agent comprises a pharmaceutically acceptable excepient, disintegrant, crosprovidone, sodium starch glycolate, corn starch, microcrystalline cellulose, cellulosic derivatives, sodium bicarbonate, and sodium alginate.
24 . The microgranule of claim 10 , further comprising a surfactant.
25 . The microgranule of claim 24 , wherein the surfactant is a non-ionic.
26 . The microgranule of claim 25 , wherein the non-ionic surfactant comprises between about 2 wt % to about 10 wt % of the microgranule.
27 . The microgranule of claim 26 , wherein the non-ionic surfactant comprises between about 4 wt % to about 8 wt % of the microgranule.
28 . The microgranule of claim 27 , wherein the non-ionic surfactant comprises about 5.0 wt % of the microgranule.
29 . The microgranule of claim 24 , wherein the non-ionic surfactant comprises a poloxamer.
30 . The microgranule of claim 25 , wherein the poloxamer comprises poloxamer 407.
31 . The microgranule of claim 10 , further comprising an antioxidant.
32 . The microgranule of claim 31 , wherein the antioxidant is selected from the group consisting of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and propyl gallate (PG).
33 . The microgranule of claim 31 , wherein the antioxidant comprises between about 0.1 wt % to about 3 wt % of the microgranule.
34 . The microgranule of claim 31 , wherein the antioxidant comprises between about 0.5 wt % to about 1 wt % of the microgranule.
35 . A pharmaceutical composition comprising the microgranule of claim 10 .
36 . The pharmaceutical composition of claim 35 , further comprising one or more pharmaceutically acceptable excepients.
37 . The pharmaceutical composition of claim 35 , wherein the composition comprises a tablet or capsule.
38 . The pharmaceutical composition of claim 37 , wherein the pharmaceutical composition comprises a disintegrant.
39 . A pharmaceutical composition comprising SD rifaximin, a polymer, a surfactant, and a release controlling agent.
40 . The pharmaceutical composition of claim 39 , comprising SD rifaximin, HPMC-AS, pluronic F127, and croscarmellose Na (CS).
41 . The pharmaceutical composition of claim 39 , wherein the pharmaceutical compositions are tablets or pills.
42 . The pharmaceutical composition of claim 39 , further comprise fillers, glidants or lubricants.
43 . The pharmaceutical composition of claim 40 , wherein the composition comprises the ratio of components set forth in Table 37.
44 . A process for producing a solid dispersion of rifaximin comprising:
making a slurry of methanol, rifaximin, a polymer and a surfactant;
spray drying the slurry
45 . A process for producing a solid dispersion of rifaximin comprising:
making a slurry of methanol, rifaximin, HPMC-AS MG and poloxamer 407; and
spray drying the slurry.
46 . A process for producing form solid dispersion of rifaximin comprising one or more of the methods listed in Tables 1, 5 or 9.