We claim:
1. A process for cleaning the inner wall of a hard gelatine capsule for use in inhalation therapy, the process comprising cleaning the capsule with a powder formulation.
2. The process according to claim 1, wherein the powder formulation is pharmaceutically acceptable.
3. The process according to one of claims 1 or 2, wherein the powder formulation constitutes an ingredient of the active substance formulation.
4. The process according to one of claims 1 or 2, wherein the powder formulation is the active substance formulation for inhalation.
5. The process according to one of claims 1 to 4, wherein the cleaning is carried out in a sealed capsule.
6. The process according to one of claims 1 to 5, wherein the cleaning is carried out without the use of solvents.
7. The process according to one of claims 1 to 6, wherein the cleaning is carried out in a gravity mixer or on a vibrating table.
8. The process according to one of claims 1 to 7, wherein the cleaning is carried out at a temperature of 15 C. to 50 C.
9. The process according to one of claims 1 to 8, wherein the mixing time is 20 to 150 minutes.
10. The process according to one of claims 1 to 9, wherein some or all of the grains of the powder formulation accumulate impurities.
11. The process according to one of claims 1 to 10, wherein some or all of the grains of the powder formulation accumulate lubricants andor mould release agents.
12. The process according to one of claims 1 to 11, wherein the content of the powder formulation is from 6% to 50% of the theoretical total capacity of the capsule.
13. The process according to one of claims 1 to 12, wherein the powder formulation contains at least one excipient with particle sizes of 10 m to 50 m in aerodynamic diameter.
14. The process according to one of claims 1 to 13, wherein the powder formulation contains lactose andor lactose monohydrate.
15. The process according to one of claims 1 to 14, the process comprising:
(a) subjecting the powder formulation to one or more screenings and mixings;
(b) transferring the powder formulation obtained from step (b) into a gelatine capsule for inhalation;
(c) agitating the gelatine capsules from step (b) in a mixing container;
(d) visually monitoring the cleaning process to a selected endpoint; and
(e) placing the gelatine capsule directly in the inhaler or optionally emptying and refilling the gelatine capsule with the active substance formulation.
16. A gelatine capsule containing a tiotropium powder formulation, the gelatine capsule obtained by shaking the filled gelatine capsules in a gravity mixer or on a vibrating table.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A method for harmonizing amplitude or energy of a plurality of consecutive laser output pulses directed at a workpiece, comprising:
generating a plurality of consecutive laser pulses along a beam path that impinges a workpiece at a beam position, the plurality of consecutive laser pulses having amplitudes or energies that vary significantly;
propagating the plurality of consecutive laser pulses through an AOM positioned along the beam path to provide a plurality of consecutive laser output pulses;
diverting a portion of each of the plurality of consecutive laser output pulses to an amplitude or energy detector;
conveying information concerning the amplitude or energy of each of the plurality of consecutive laser output pulses directly or indirectly to an AOM controller; and
modulating an RF signal applied to the AOM to affect the amplitude or energy of a given one of the plurality of consecutive laser output pulses in response to the information concerning the amplitude or energy of one or more of the plurality of consecutive laser output pulses preceding the given one of the plurality of consecutive laser output pulses.
2. The method of claim 1 in which the beam path impinges the AOM at an angle that is at or in proximity to a Bragg angle with respect to a beam entrance surface of the AOM, the RF signal applied to the AOM is frequency modulated to affect an exit angle of the given one of the plurality of consecutive laser output pulses that propagates along the beam path to the workpiece, and the RF signal is modulated to affect the amplitude or energy of the given one of the plurality of consecutive laser output pulses to compensate for deviations from Bragg efficiency resulting from a shift of exit angle of the beam path from the Bragg angle.
3. A method for employing an AOM to harmonize amplitude or energy of a plurality of consecutive laser output pulses directed at a workpiece, the AOM being suited for positioning along a beam path between a laser and a workpiece, the AOM having a beam entrance surface, a beam exit surface, and a first transducer that is positioned on a first transducer surface of the AOM and that modulates within a first transducer modulation zone, the first transducer surface being in a first plane that is transverse to the beam entrance surface, comprising:
generating a laser beam along a beam path that impinges a workpiece;
propagating the laser beam through the AOM positioned along the beam path, the beam path impinging the AOM at an entrance angle that is at or in proximity to a Bragg angle with respect to the beam entrance surface or the first transducer modulation zone, and the beam path exiting the AOM at a first exit angle;
controlling a first frequency of a first RF signal applied to the first transducer that modulates within the first transducer modulation zone that traverses the beam path to affect the first exit angle of the beam path along a first workpiece axis with respect to a surface of the workpiece; and
controlling a first amplitude of the first RF signal applied to the first transducer to compensate for deviation from Bragg efficiency resulting from a first shift of the first exit angle of the beam path from the Bragg angle.
4. The method of claim 3 further comprising:
controlling a second frequency of a second RF signal applied to a second transducer positioned on a second transducer surface of the AOM, the second transducer surface being in a second plane that is transverse to the beam entrance surface and the first plane, the second transducer modulating within a second transducer modulation zone that traverses the beam path to affect a second exit angle of the beam path along a second workpiece axis that is transverse to the first workpiece axis with respect to a surface of the workpiece, the second transducer modulation zone being transverse to the first transducer modulation zone;
coordinating the first and second frequencies to deflect the beam path in both the first and second workpiece axes at a cooperative deflection angle resulting from the first and second exit angles imparted by the first and second transducers in response to the first and second RF signals; and
controlling a second amplitude of the second RF signal applied to the second transducer to compensate for deviation from Bragg efficiency resulting from a second shift of the second exit angle of the beam path from the Bragg angle.
5. The method of claim 4 in which the first and second transducer surfaces are generally orthogonal.
6. The method of claim 4 in which the first and second frequencies are different.
7. The method of claim 3 in which the beam path initially impinges the workpiece at a nominal beam position and in which the first exit angle deflects with the AOM the beam path from the nominal beam position to impinge the workpiece at a desired beam position.
8. The method of claim 3 further comprising:
controlling a second frequency of a second RF signal applied to a second transducer positioned on a second transducer surface of the AOM, the second transducer surface being in a second plane that is transverse to the beam entrance surface, the second transducer modulating within a second transducer modulation zone that traverses the beam path to affect a second exit angle of the beam path along the first workpiece axis, the second transducer being spaced-apart and oriented at a small angle with respect to the first transducer such that the first and second transducer modulation zones are nonparallel;
coordinating the first and second frequencies to deflect the beam path at a cooperative deflection angle resulting from the first and second exit angles imparted by the first and second transducers in response to the first and second RF signals; and
controlling a second amplitude of the second RF signal applied to the second transducer to compensate for deviation from Bragg efficiency resulting from a second shift of the second exit angle of the beam path from the Bragg angle.
9. The method of claim 8 in which the first and second transducer modulation zones are non-overlapping.
10. The method of claim 8 in which the first and second planes are transverse, in which the beam entrance surface and the beam exit surface have planes that are nonparallel, in which the first transducer modulation zone is generally parallel to the beam entrance surface, and in which the second transducer modulation zone is generally parallel to the beam exit surface.
11. The method of claim 8 in which the small angle is from about 0.1 to about 3 degrees.
12. The method of claim 11 in which the small angle is from about 0.5 to about 2.5 degrees.
13. The method of claim 8 in which the first and second frequencies are different.
14. The method of claim 8 in which the cooperative deflection angle has a range that comprises up to at least 100 milliradians with respect to the Bragg angle.
15. The method of claim 8 in which the first transducer is responsive to a high frequency driver for larger Bragg angle range and the second transducer is responsive to a lower frequency driver for smaller Bragg angle range.
16. The method of claim 3, further comprising:
providing slow and fast movement-controlling signals from a positioning signal processor;
controlling with a slow positioner driver a large range of relative beam-directing movement of a translation stage, generally along a translation axis in response to the slow movement-controlling signal;
controlling with the first andor second transducers a small range of relative beam-directing movement of the AOM in response to the fast movement-controlling signal;
effecting the large range of relative beam-directing movement between the beam path and the workpiece on the translation stage; and
effecting with the AOM the small range of relative beam-directing movement between the beam path and the workpiece to impinge the workpiece at a desired beam position.
17. The method of claim 3 in which the laser beam includes pulses having a maximum peak power andor energy, further comprising:
employing a laser overhead power budget such that a reduced peak power andor energy is permitted to propagate through the AOM and along the beam path whenever a working pulse is desired to impinge the workpiece and the first exit angle is at or in proximity to the Bragg angle, the reduced peak power andor energy being less than the maximum peak power andor energy; and
employing a higher compensated peak power andor energy to propagate through the AOM and along the beam path whenever a working pulse is desired to impinge the workpiece and the first exit angle is shifted from the Bragg angle, the higher compensated peak power andor energy being greater than the reduced peak power andor energy and less than the maximum peak power andor energy.
18. An AOM control system for controlling an AOM suited to be positioned along a beam path between a laser and a workpiece; the AOM having a beam entrance surface, a beam exit surface, and a first transducer that is positioned on a first transducer surface of the AOM and that modulates within a first transducer modulation zone; the first transducer surface being in a first plane that is transverse to the beam entrance surface; the AOM also providing a Bragg angle with respect to the beam entrance surface, first transducer modulation zone, andor the beam exit surface, comprising:
a first RF driver including or in communication with a variable frequency controller adapted to apply a first frequency of a first RF signal to the first transducer to shift the beam path away from the Bragg angle at the first transducer modulation zone to affect a deflection angle of the beam path along a first Cartesian axis, the first RF driver also being adapted to adjust a first amplitude of the first RF signal applied to the first transducer; and
a controller for delivering information concerning Bragg efficiency compensation data to the first RF driver to adjust the first amplitude to compensate for deviation from Bragg efficiency resulting from a shift of the beam path from the Bragg angle.
19. The AOM control system of claim 18 in which the Bragg efficiency compensation data comprises a lookup table.
20. The AOM control system of claim 18 in which the Bragg efficiency compensation data comprises an algorithm based on a sin c function.
21. The AOM control system of claim 18 in which the laser beam includes pulses having a maximum peak power andor energy, a laser overhead power budget is employed such that a reduced peak power andor energy is permitted to propagate through the AOM and along the beam path whenever a working pulse is desired to impinge the workpiece and the deflection angle is at or in proximity to the Bragg angle, wherein the reduced peak power andor energy is less than the maximum peak power andor energy; and in which a higher compensated peak power andor energy is permitted to propagate through the AOM and along the beam path whenever a working pulse is desired to impinge the workpiece and the deflection angle is shifted from the Bragg angle, wherein the higher compensated peak power andor energy is greater than the reduced peak power andor energy and less than the maximum peak power andor energy.