Claims for Patent: 8,580,306

Summary for Patent: 8,580,306

Title:	Particles for use in a pharmaceutical composition
Abstract:	The invention provides a method of making a composition for inhalation which includes the step of mixing particles of additive material having a diameter of not more than 2 .mu.m with active particles, wherein the additive material is suitable for promoting the dispersal of active particles upon aerolization of a dry, powder in a dry powder inhaler.
Inventor(s):	Staniforth; John Nicholas (Bath, GB), Morton; David Alexander Vodden (Bath, GB)
Assignee:	Vectura Limited (Chippenham, GB)
Application Number:	10/433,135
Patent Claims:	1. A method of making a composition for inhalation comprising reducing in size particles of additive material to produce particles with an MMAD of not more than 2 .mu.m; and mixing the additive particles with active particles, wherein the additive material is suitable for promoting dispersal of active particles upon aerosolisation of a dry powder in a dry powder inhaler; wherein said additive material is soft, having an indentation hardness of not more than 100 MPa; and wherein the step of reducing in size particles of additive material is performed dry; wherein the method further comprises the step of fusing the particles of additive material to the surfaces of the active particles by compressing the mixture of active and additive particles using a milling process selected from ball milling, mechano-fusion, a cyclomix method, a hybridiser method, agitator bead milling, jet milling, pin milling, hammer milling, knife milling, and ultracentrifugal milling. 2. A method as claimed in claim 1, in which the additive particles have a diameter of not more than 1.5 .mu.m. 3. A method as claimed in claim 1, wherein the additive material is also a hydrophobic material suitable for delaying dissolution of an active substance in a lung. 4. A method as claimed in claim 1, wherein the additive material comprises magnesium stearate. 5. A method as claimed in claim 1, in which the additive material comprises a phospholipid. 6. A method as claimed in claim 5, wherein said additive material is lecithin. 7. A method as claimed in claim 1 in which the additive particles are agglomerated. 8. A method as claimed in claim 1 in which the additive particles have a bulk density not more than 0.4 gcm.sup.-3. 9. A method as claimed in claim 1 in which the additive particles are in a form of flakes having a thickness of not more than 0.5 .mu.m. 10. A method as claimed in claim 1 further comprising a step of providing large particles of additive material having a MMAD of greater than 2 .mu.m and the step of reducing the size of those particles such that the MMAD of the resulting particles is less than 2 .mu.m. 11. A method as claimed in claim 10 in which the particles of active material are also present during the step of reducing the size of the particles of additive material. 12. A composition for inhalation comprising particles of an active substance and additive particles, the composition prepared by a method as claimed in claim 1, wherein the particles have aerodynamic diameters in the range of 2 to 0.05 .mu.m. 13. A composition as claimed in claim 12, which is a powder and is suitable for use in a dry powder inhaler. 14. A composition as claimed in claim 12 further comprising a propellant and is suitable for use in a pressurized metered dose inhaler. 15. A dry powder inhaler comprising a composition as claimed in claim 13. 16. A pressurized metered dose inhaler which comprises a composition as claimed in claim 14. 17. A method of promoting the dispersal of active particles of a composition for inhalation upon aerosolisation of an inhaler, the method comprising reducing in size particles of additive material to produce particles with an MMAD of not more than 2 .mu.m; mixing the additive particles with active particles; and fusing the particles of additive material to the surfaces of the active particles, by compressing the mixture of active and additive particles using a milling process selected from ball milling, mechano- fusion, a cyclomix method, a hybridiser method, agitator bead milling, jet milling, pin milling, hammer milling, knife milling, and ultracentrifugal milling; wherein said additive material is soft, having an indentation hardness of not more than 100 MPa, wherein the step of reducing in size of particles of additive material is performed dry. 18. A method of delaying dissolution of active particles of a composition for inhalation; the method comprising reducing in size particles of additive material to produce particles with an MMAD of not more than 2 .mu.m; mixing the additive particles with active particles; and fusing the particles of additive material to the surfaces of the active particles, by compressing the mixture of active and additive particles using a milling process selected from ball milling, mechano-fusion, a cyclomix method, a hybridiser method, agitator bead milling, jet milling, pin milling, hammer milling, knife milling, and ultracentrifugal milling; wherein the additive material is soft, having an indentation hardness of not more than 100 MPa, wherein the step of reducing in size particles of additive material is performed dry, said delayed dissolution is as compared to the dissolution of the active particles in the absence of the additive material. 19. A method of therapy comprising a step of administering a composition for inhalation as claimed in claim 12 to a human being or animal in need thereof.