Sulfoalkyl ether cyclodextrin compositions and methods of preparation thereof
View Patent ↗A particulate SAE-CD composition is provided. The SAE-CD composition has an advantageous combination of physical properties not found in known solid forms of SAECD. In particular, the SAE-CD composition possesses an advantageous physicochemical and morphological property profile such that it can be tailored to particular uses. The SAE-CD composition of the invention has improved flow and dissolution performance as compared to known compositions of SAE-CD.
1. A composition comprising an excipient and a sulfoalkyl ether cyclodextrin composition, wherein the sulfoalkyl ether cyclodextrin composition comprises:
(a) sulfoalkyl ether cyclodextrin;
(b) no more than about 20% by weight moisture;
(c) a bulk density of about 0.38 g/cm 3 to about 0.66 g/cm 3 ;
(d) a tapped density of about 0.49 g/cm 3 to about 0.75 g/cm 3 , wherein the tapped density of the sulfoalkyl ether cyclodextrin composition is higher than the bulk density; and
(e) a gravitational-flow minimum orifice diameter of about 3 mm to about 12 mm; and
wherein the sulfoalkyl ether cyclodextrin composition comprises agglomerated particles,
wherein the agglomerated particles are produced by a process comprising:
(i) forming a fluidized bed of SAE-CD particles in a drying chamber of a fluidized bed spray dryer apparatus with an attached 3-chamber fluidization bed;
(ii) recycling fine particles from the fluidized bed back into the drying chamber at a location adjacent to a liquid feed atomizer; and
(iii) collecting agglomerated particles from the third chamber of the 3-chamber fluidization bed.
2. The composition of claim 1 , wherein the sulfoalkyl ether cyclodextrin is a compound, or a mixture of compounds, of the Formula 1:
wherein:
n is 4, 5, or 6;
R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are each, independently, O − or a O—(C 2-6 alkylene)—SO 3 − group, wherein at least one of R 1 and R 2 is, independently, the O—(C 2 -C 6 alkylene)—SO 3 − group; and
S 1 , S 2 , S 3 , S 4 , S 5 , S 6 , S 7 , S 8 , and S 9 , are each, independently, a pharmaceutically acceptable cation.
3. The composition of claim 1 , wherein the sulfoalkyl ether cyclodextrin composition comprises a bulk density of about 0.55 g/cm 3 to about 0.66 g/cm 3 and a tapped density of about 0.66 g/cm 3 to about 0.75 g/cm 3 .
4. The composition of claim 1 , wherein the sulfoalkyl ether cyclodextrin composition comprises a bulk density of about 0.38 g/cm 3 to about 0.55 g/cm 3 and a tapped density of about 0.49 g/cm 3 to about 0.66 g/cm 3 .
5. The composition of claim 1 , wherein the sulfoalkyl ether cyclodextrin composition comprises a gravitational-flow minimum orifice diameter of about 10 mm or less.
6. The composition of claim 1 , wherein the sulfoalkyl ether cyclodextrin composition comprises a true density of about 1.1 g/cm 3 to about 1.5 g/cm 3 .
7. The composition of claim 1 , wherein the sulfoalkyl ether cyclodextrin composition comprises a CARR's index of about 12% to about 24%.
8. The composition of claim 1 , wherein the sulfoalkyl ether cyclodextrin composition comprises particles with a mean particle diameter of about 75 microns to about 200 microns.
9. The composition of claim 8 , wherein at least 90% of the particle volume of the sulfoalkyl ether cyclodextrin composition comprises particles having calculated diameters greater than or equal to about 25 microns.
10. The composition of claim 1 , wherein the sulfoalkyl ether cyclodextrin composition comprises a moisture content of about 2% to about 3% by weight and a compression crushing strength of about 1.0 kP to about 20 kP when compressed into a tablet using a Pmax of about 30 MPa to about 275 MPa.
11. The composition of claim 1 , wherein the sulfoalkyl ether cyclodextrin composition comprises a moisture content of about 5% to about 6% by weight and a compression crushing strength of about 0.5 to about 11 kP when compressed into a tablet using a Pmax of about 15 MPa to about 70 MPa.
12. The composition of claim 1 , wherein 2.5 g of the sulfoalkyl ether cyclodextrin composition has an average dissolution time of about 2 mm to about 4.5 mm when placed in water.
13. The composition of claim 1 , wherein the composition is a pharmaceutical composition further comprising an active agent.
14. A pharmaceutical dosage form comprising a sulfoalkyl ether cyclodextrin composition and an excipient, wherein the sulfoalkyl ether cyclodextrin composition comprises:
(a) sulfoalkyl ether cyclodextrin;
(b) no more than about 20% by weight moisture;
(c) a bulk density of about 0.38 g/cm 3 to about 0.66 g/cm 3 ;
(d) a tapped density of about 0.49 g/cm 3 to about 0.75 g/cm 3 , wherein the tapped density of the sulfoalkyl ether cyclodextrin composition is higher than the bulk density; and
(e) a gravitational-flow minimum orifice diameter of about 3 mm to about 12 mm;
wherein the sulfoalkyl ether cyclodextrin composition comprises agglomerated particles,
wherein the agglomerated particles are produced by a process comprising:
(i) forming a fluidized bed of SALE-CD particles in a drying chamber of a fluidized bed spray dryer apparatus with an attached 3-chamber fluidization bed;
(ii) recycling fine particles from the fluidized bed back into the drying chamber at a location adjacent to a liquid feed atomizer; and
(iii) collecting agglomerated particles from the third chamber of the 3-chamber fluidization bed, and
wherein the dosage form is selected from the group consisting of a tablet, liquid, suspension, emulsion, film, laminate, pellet, powder, bead, granule, suppository, ointment, cream, capsule, constitutable powder, dry powder inhaler, saché, troche, and lozenge.
15. The dosage form of claim 14 , wherein the dosage form is a powder.
16. The dosage form of claim 14 , wherein the dosage form is a tablet.
17. The dosage form of claim 16 , wherein the tablet is selected from the group consisting of a controlled release tablet, an extended release tablet, a compressed tablet, a compressed rapid release tablet, and an orodispersable immediate release tablet.
18. A pharmaceutical dosage form comprising a sulfoalkyl ether cyclodextrin composition, an excipient, and an active agent, wherein the sulfoalkyl ether cyclodextrin composition comprises:
(a) sulfoalkyl ether cyclodextrin;
(b) no more than about 20% by weight moisture;
(c) a bulk density of about 0.38 g/cm 3 to about 0.66 g/cm 3 ;
(d) a tapped density of about 0.49 g/cm 3 to about 0.75 g/cm 3 , wherein the tapped density of the sulfoalkyl ether cyclodextrin composition is higher than the bulk density; and
(e) a gravitational-flow minimum orifice diameter of about 3 mm to about 12 mm;
wherein the sulfoalkyl ether cyclodextrin composition comprises agglomerated particles,
wherein the agglomerated particles are produced by a process comprising:
(i) forming a fluidized bed of SAE-CD particles in a drying chamber of a fluidized bed spray dryer apparatus with an attached 3-chamber fluidization bed;
(ii) recycling fine particles from the fluidized bed back into the drying chamber at a location adjacent to a liquid feed atomizer; and
(iii) collecting agglomerated particles from the third chamber of the 3-chamber fluidization bed, and
wherein the dosage form is selected from the group consisting of a tablet, liquid, suspension, emulsion, film, laminate, pellet, powder, bead, granule, suppository, ointment, cream, capsule, constitutable powder, dry powder inhaler, saché, troche, and lozenge.