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US-12616659-B2 - Therapeutic agent nanoparticles and methods of preparation

US12616659B2US 12616659 B2US12616659 B2US 12616659B2US-12616659-B2

Abstract

Provided herein is a coated particle comprising: (i) a microparticle that comprises a pharmaceutically acceptable excipient and (ii) nanoparticles of a therapeutic agent, wherein the surface of the microparticle is coated with the nanoparticles. Also provided herein is a pharmaceutical composition comprising the coated particle. Furthermore, provided herein are methods of their preparation.

Inventors

  • Kay Olmstead
  • Saeyeon Lee
  • Seok-Keun Koh

Assignees

  • NANO PHARMASOLUTIONS, INC.

Dates

Publication Date
20260505
Application Date
20230524

Claims (18)

  1. 1 . A method of preparing coated particles, each particle consisting of: (i) a microparticle that consists of a pharmaceutically acceptable excipient and (ii) nanoparticles of a therapeutic agent, wherein the nanoparticles have an average particle size ranging from about 10 to about 500 nm; comprising the steps of: a. vaporizing the therapeutic agent at a first predetermined temperature under a predetermined vacuum pressure to form a vapor; and b. depositing the vapor on the surfaces of the microparticles at a predetermined agitation speed and a second predetermined temperature under the predetermined vacuum pressure to form the nanoparticles on the surfaces of the microparticles, thus forming the coated particles; wherein the second predetermined temperature is ranging from about 10 to about 100° C.
  2. 2 . The method of claim 1 , wherein the first predetermined temperature is ranging from about 50 to about 250° C.
  3. 3 . The method of claim 1 , wherein the predetermined vacuum pressure is ranging from about 10 −3 to about 10 −9 torr.
  4. 4 . The method of claim 1 , wherein the predetermined agitation speed is ranging from about 50 to about 100 rpm.
  5. 5 . The method of claim 1 , wherein the pharmaceutically acceptable excipient is a hydrophilic excipient.
  6. 6 . The method of claim 1 , wherein the pharmaceutically acceptable excipient is a sugar alcohol.
  7. 7 . The method of claim 1 , wherein the pharmaceutically acceptable excipient is mannitol, sorbitol, xylitol, or a mixture thereof.
  8. 8 . The method of claim 1 , wherein the pharmaceutically acceptable excipient is mannitol.
  9. 9 . The method of claim 1 , wherein the pharmaceutically acceptable excipient is a sugar.
  10. 10 . The method of claim 1 , wherein the pharmaceutically acceptable excipient is dextrose.
  11. 11 . The method of claim 10 , wherein the pharmaceutically acceptable excipient is D-dextrose.
  12. 12 . The method of claim 1 , wherein the microparticle has an average particle size ranging from about 1 to about 100 μm, from about 1 to about 50 μm, or from about 1 to about 25 μm.
  13. 13 . The method of claim 1 , wherein the therapeutic agent is a BCS class II or IV compound.
  14. 14 . The method of claim 1 , wherein the therapeutic agent has a melting point of no greater than about 300° C.
  15. 15 . The method of claim 1 , wherein the coated particle contains the nanoparticles in an amount ranging from about 0.1 to about 25% by weight.
  16. 16 . The method of claim 1 , wherein the coated particle has an average particle size ranging from about 1 to about 100 μm, from about 1 to about 50 μm, or from about 1 to about 25 μm.
  17. 17 . The method of claim 1 , wherein the therapeutic agent is cannabidiol, carbamazepine, ibuprofen, nifedipine, piroxicam, plumbagin, verapamil, or zileuton.
  18. 18 . A method of preparing nanoparticles of a therapeutic agent, wherein the nanoparticles have an average particle size ranging from about 10 to about 500 nm; comprising the steps of: a. vaporizing the therapeutic agent at a first predetermined temperature under a predetermined vacuum pressure to form a vapor; and b. depositing the vapor on the surface of a microparticle consisting of a pharmaceutically acceptable excipient at a predetermined agitation speed and a second predetermined temperature under the predetermined vacuum pressure to form the nanoparticles on the surface of the microparticle; wherein the second predetermined temperature is ranging from about 10 to about 100° C.

Description

CROSS REFERENCE TO RELATED APPLICATION This application is a divisional application of U.S. application Ser. No. 17/178,456, filed Feb. 18, 2021; which claims the benefit of U.S. Provisional Application No. 62/978,773, filed Feb. 19, 2020; the disclosure of each of which is incorporated herein by reference in its entirety. FIELD Provided herein is a coated particle comprising: (i) a microparticle that comprises a pharmaceutically acceptable excipient and (ii) nanoparticles of a therapeutic agent, wherein the surface of the microparticle is coated with the nanoparticles. Also provided herein is a pharmaceutical composition comprising the coated particle. Furthermore, provided herein are methods of their preparation. BACKGROUND Poor water solubility presents a major challenge in drug formulation. Savjani et al., ISRN Pharm. 2012, 2012, 195727. More than 70% of small-molecule new chemical entities (NCE) and about 40% of the currently marketed drugs have poor water solubility. Kollipara and Gandhi, Acta Pharm. Sin. B 2014, 4, 333-349. Various techniques have been developed to enhance the solubility of poorly soluble drugs, including particle size reduction, crystal engineering, salt formation, solid dispersion, use of surfactant, and complexation. See, e.g., Id.; Challa et al., AAPS PharmSciTech 2005, 6, E329-E357; Salama, Drug Deliv. Transl. Res. 2020, 10, 1-12. Despite advances in formulation technology, poor water solubility still remains a major hurdle in small-molecule drug development. Therefore, there is a need for an effective and robust technology to formulate poorly soluble small molecules for therapeutic applications. SUMMARY OF THE DISCLOSURE Provided herein is a coated particle comprising: (i) a microparticle that comprises a pharmaceutically acceptable excipient and (ii) nanoparticles, each comprising a therapeutic agent; wherein the microparticle is surface-coated with the nanoparticles. Also provided herein is a pharmaceutical composition comprising coated particles, each particle comprising: (i) a microparticle that comprises a pharmaceutically acceptable excipient and (ii) nanoparticles of a therapeutic agent, wherein the microparticle is surface-coated with the nanoparticles. Additionally, provided herein is a method of preparing coated particles, each particle comprising: (i) a microparticle that comprises a pharmaceutically acceptable excipient and (ii) nanoparticles of a therapeutic agent, comprising the steps of: a. vaporizing the therapeutic agent at a first predetermined temperature under a predetermined vacuum pressure to form a vapor; andb. depositing the vapor on the surfaces of the microparticles at a predetermined agitation speed and a second predetermined temperature under the predetermined vacuum pressure to form the nanoparticles on the surfaces of the microparticles, thus forming the coated particles. Furthermore, provided herein is a method of preparing nanoparticles of a therapeutic agent, comprising the steps of: a. vaporizing the therapeutic agent at a first predetermined temperature under a predetermined vacuum pressure to form a vapor; andb. depositing the vapor on the surface of a microparticle comprising a pharmaceutically acceptable excipient at a predetermined agitation speed and a second predetermined temperature under the predetermined vacuum pressure to form the nanoparticles on the surface of the microparticle. Provided herein are coated particles, each particle comprising: (i) a microparticle that comprises a pharmaceutically acceptable excipient and (ii) nanoparticles of a therapeutic agent; wherein the coated particles are prepared by a method comprising the steps of: a. vaporizing the therapeutic agent at a first predetermined temperature under a predetermined vacuum pressure to form a vapor; andb. depositing the vapor on the surfaces of the microparticles at a predetermined agitation speed and a second predetermined temperature under the predetermined vacuum pressure to form the nanoparticles on the surfaces of the microparticles, thus forming the coated particles. Provided herein are nanoparticles of a therapeutic agent, which are prepared by a method comprising the steps of: a. vaporizing the therapeutic agent at a first predetermined temperature under a predetermined vacuum pressure to form a vapor; andb. depositing the vapor on the surface of a microparticle comprising a pharmaceutically acceptable excipient at a predetermined agitation speed and a second predetermined temperature under the predetermined vacuum pressure to form the nanoparticles on the surface of the microparticle. Provided herein is a pharmaceutical composition comprising coated particles, each particle comprising: (i) a microparticle that comprises a pharmaceutically acceptable excipient and (ii) nanoparticles of a therapeutic agent; wherein the coated particles are prepared by a method comprising the steps of: a. vaporizing the therapeutic agent at a first predetermined temperature und