IP Library › Granted Patent US 12,233,163
Granted Patent B2
US 12,233,163 · App. 17/666,608 · Granted Feb 25, 2025

Crystalline microspheres and the process of manufacturing the same

Inventors: Cecil W. Propst (Norton Shores, MI); Marc W. Meadows (Grand Haven, MI); Michael S. Todd (Grand Haven, MI)
Assignee: SPI Pharma, Inc.
A61K9/1623A61K9/16Y10T428/2982
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Quick Facts
Patent No.
US 12,233,163
App. No.
17/666,608
Granted
Feb 25, 2025
Kind
B2
Abstract

The present invention relates to microspheres comprising a core material, wherein the microsphere is perfectly spherical and has a moisture content less than 1%, and the method of manufacturing the same. The present invention is useful in the manufacture of sustained and modified release active pharmaceutical ingredient (API) microspheres, as a free flowing excipient for mini-tablets and in the manufacture of API dispersions.

Claims (23)

1. A microsphere comprising a core material, wherein the microsphere has a circularity greater than 0.95, an aspect ratio greater than 0.95, a solidity greater than 0.99, and lacks porosity.

2. The microsphere of claim 1 , wherein the microsphere has a mean particle size from about 10 μm to about 500 μm.

3. The microsphere of claim 2 , wherein the microsphere has a mean particle size from about 10 μm to about 20 μm.

4. The microsphere of claim 3 , wherein the microsphere has a moisture content of 0.5% or less.

5. The microsphere of claim 1 , wherein a plurality of microspheres has a particle size distribution of 2.8 or less.

6. The microsphere of claim 5 , wherein the plurality of microspheres has a particle size distribution of 2.0 or less.

7. The microsphere of claim 5 , wherein the plurality of microspheres has a particle size distribution of 1.5 or less.

8. The microsphere of claim 5 , wherein the plurality of microspheres has a particle size distribution of 1.0.

9. The microsphere of claim 1 , wherein the microsphere has a surface with ridges 10 μm or less.

10. The microsphere of claim 1 , wherein the microsphere has a skeletal density from about 1.4595 g/cc to about 1.4651 g/cc.

11. The microsphere of claim 1 , wherein the microsphere has a moisture content of 0.5% or less.

12. The microsphere of claim 11 , wherein the microsphere has a moisture content of 0.1% or less.

13. The microsphere of claim 11 , wherein the microsphere has a moisture content of 0.0%.

14. The microsphere of claim 1 , wherein the microsphere is water soluble.

15. The microsphere of claim 1 , wherein the microsphere comprises a single core material.

16. The microsphere of claim 15 , wherein the single core material is mannitol.

17. The microsphere of claim 1 , wherein the microsphere comprises a 100% crystalline core.

18. The microsphere of claim 1 , wherein the microsphere further comprises an active pharmaceutical ingredient.

19. The microsphere of claim 1 , wherein the core material is a polyol.

20. The microsphere of claim 19 , wherein the polyol is mannitol.

21. The microsphere of claim 1 , wherein the microsphere lack internal voids.

22. A composition comprising the microsphere of claim 1 .

23. The composition of claim 22 further comprising an active pharmaceutical ingredient.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 21, 2025
From: PROPST, CECIL W.; MEADOWS, MARC W.; TODD, MICHAEL S.
To: SPI PHARMA, INC.
Reel/Frame 069948/0545 →
Continuity (6)
Continuation 16371262 · Apr 1, 2019
Continuation 14809362 · Jul 27, 2015
Continuation 13870556 · Apr 25, 2013
Provisional Application 61783603 · Mar 14, 2013
Provisional Application 61638073 · Apr 25, 2012
Related Publication 20220151932A1 · May 19, 2022
References Cited (73)
US 4820627A · McGeehan · 1989 [cited by applicant]
US 5679398A · Serpelloni et al. · 1997 [cited by applicant]
US 5780055A · Habib et al. · 1998 [cited by applicant]
US 6235947B1 · Yoshinari · 2001 [cited by examiner]
US 6248363B1 · Patel et al. · 2001 [cited by applicant]
US 6264989B1 · Kato et al. · 2001 [cited by applicant]
US 6692768B1 · Ishibashi et al. · 2004 [cited by applicant]
US 6855361B2 · Rapp et al. · 2005 [cited by applicant]
US 7118765B2 · Norman et al. · 2006 [cited by applicant]
US 7582154B2 · Propst et al. · 2009 [cited by applicant]
US 7625507B2 · Ray et al. · 2009 [cited by applicant]
US 8545889B2 · Norman et al. · 2013 [cited by applicant]
US 8617588B2 · Tillotson et al. · 2013 [cited by applicant]
US 9089487B2 · Propst et al. · 2015 [cited by applicant]
US 20030129250A1 · Batycky · 2003 [cited by examiner]
US 20060024379A1 · Brown · 2006 [cited by examiner]
US 20060057213A1 · Larhrib · 2006 [cited by examiner]
US 20060263423A1 · Norman et al. · 2006 [cited by applicant]
US 20070092562A1 · Norman et al. · 2007 [cited by applicant]
US 20080107729A1 · Amin et al. · 2008 [cited by applicant]
US 20080181932A1 · Bortz et al. · 2008 [cited by applicant]
US 20100068276A1 · Friesen et al. · 2010 [cited by applicant]
US 20100092568A1 · Lerner et al. · 2010 [cited by applicant]
US 20100167052A1 · Satomi · 2010 [cited by examiner]
US 20100247665A1 · Takahashi · 2010 [cited by applicant]
US 20110135927A1 · Salomi et al. · 2011 [cited by applicant]
US 20110269874A1 · Mukai et al. · 2011 [cited by applicant]
US 20140023707A1 · Norman et al. · 2014 [cited by applicant]
US 20140044793A1 · Goll et al. · 2014 [cited by applicant]
US 20140093574A1 · Tillotson et al. · 2014 [cited by applicant]
US 20140099372A1 · Propst et al. · 2014 [cited by applicant]
US 20150140097A1 · Propst et al. · 2015 [cited by applicant]
EP 0913148 · 1999 [cited by applicant]
EP 0812187 · 2003 [cited by applicant]
JP H1092403 · 1999 [cited by applicant]
JP 2007508240 · 2007 [cited by applicant]
JP 2007217651 · 2007 [cited by applicant]
JP 2009544812 · 2009 [cited by applicant]
JP 2011157348 · 2011 [cited by applicant]
WO 02035991A2 · 2002 [cited by applicant]
WO 2005009375 · 2005 [cited by applicant]
WO 2008016684A1 · 2008 [cited by applicant]
WO 2008146590 · 2008 [cited by applicant]
WO 2010128300A1 · 2010 [cited by applicant]
WO 2010021300A1 · 2012 [cited by applicant]
WO 2012036953 · 2012 [cited by applicant]
P. Kippax, “Particle size analysis,” PharmTech.com Advancing Development and Manufacturing, Pharmaceutical Technology Europe PTE, vol. 21, Issue 4, <http://www.pharmtech.com/particle-size-analysis ?id=&sk=&date=&&pageID… [cited by examiner]
Z. Sun et al., “Particle Size Specifications for Solid Oral Dosage Forms: A Regulatory Perspective,” American Pharmaceutical Review, May 1, 2010, <http://www.americanpharmaceuticalreview.com/Featured-Articles/36779-Part… [cited by examiner]
Unfavourable Opinion issued in BR. Appl. No. BR122022012795-9, mailed Sep. 12, 2022, 6 pages. [cited by applicant]
Unfavourable Opinion issued in BR. Appl. No. BR122022012795-9, mailed Jan. 5, 2023, 8 pages. [cited by applicant]
Notification of Reasons for Rejection, dated Dec. 1, 2017, for Japanese Patent Application No. 2015-509147, with English translation. [cited by applicant]
Clinic All-Round, 1999, vol. 48, No. 6, pp. 1577-1578. [cited by applicant]
J. Pharmacol. Exp. Ther., 1977, vol. 201, No. 3, pp. 762-768. [cited by applicant]
Examination Report, dated Dec. 19, 2017, for Indian Patent Application No. 9416/DELNP/2014. [cited by applicant]
Translation of Official Action for Mexican Patent Application No. MX/a/2014/012805. [cited by applicant]
Office Action, dated May 31, 2017, for co-pending U.S. Appl. No. 14/397,011. [cited by applicant]
Notification of Reasons for Rejection, dated Jan. 11, 2017, for Japanese Patent Application No. 2015-509147, with English translation. [cited by applicant]
Examination Report, dated Dec. 11, 2015, for Canadian Patent Application No. 2,871,429. [cited by applicant]
Non-Final Office Action, dated Aug. 18, 2016, for co-pending U.S. Appl. No. 14/397,011. [cited by applicant]
Non-Final Office Action, dated May 6, 2014, for parent U.S. Appl. No. 13/870,556. [cited by applicant]
Final Office Action, dated Sep. 16, 2014, for parent U.S. Appl. No. 13/870,556. [cited by applicant]
Examination Report, dated Jun. 22, 2016, for Canadian Patent Application No. 2,871,429. [cited by applicant]
Non-Final Office Action, dated Nov. 18, 2015, for co-pending U.S. Appl. No. 14/397,011. [cited by applicant]
Extended European Search Report for European Patent Application No. 13781897.7, dated Aug. 18, 2015. [cited by applicant]
Chambi et al., “Solid lipid microparticles containing water-soluble compounds of different molecular mass: Production, characterisation and release profiles.” Food Research International 41 (2008) 229-236. [cited by applicant]
Luciani et al., “Solvent and melting induced microspheres sintering techniques: a comparative study of morphology and mechanical properties.” J Mater Sci: Mater Med (2011) 22:2019-2028. [cited by applicant]
International Search Report and Written Opinion dated Sep. 13, 2013 for International Application No. PCT/US2013/038257. [cited by applicant]
Hideki Takahashi, “Properties of spherical mannitol on pharmaceutical preparation.” Pharm Tech Japan, vol. 27, No. 12 (2011), 15(2361)-17(2363). [cited by applicant]
S. Adi et al., “Agglomerate strength and dispersion of pharmaceutical powders,” Journal of Aerosol Science 42 (2011) 285-294. [cited by applicant]
P. Kippax, “Particle size analysis,” PharmTech.com Advancing Development and Manufacturing, Pharmaceutical Technology Europe PTE, vol. 21, Issue 4, <http://www.pharmtech.com/particle-size-analysis?d=&sk=&date=&&page1D=1… [cited by applicant]
Technical Report for Brazil Patent Application No. BR112014026351-5, dated Jul. 26, 2019 (with translation). [cited by applicant]
Decision of Refusal of Japanese Patent Application No. 2015-509147, dated Nov. 9, 2018 (with translation). [cited by applicant]
Search Report and Opinion for European Patent Application No. 19163519.2, dated Nov. 27, 2019. [cited by applicant]