1. A filtering chip conveyor comprising:
a conveyor tank arranged to retain cutting fluid containing chips,
a continuous conveyor belt at least partly disposed inside the conveyor tank, the belt being arranged to rotate and to turn at a tail end and at a discharge end, with a space between upper and lower flights of the belt, so as to transport chips on the upper flight towards the discharge end, to be discharged off the conveyor,
at least one filter box arranged between the upper and the lower flights of the belt,
at least one filter plate arranged in the filter box, the filter plate comprising a filtration region having a plurality of openings for permitting cutting fluid to pass through the filter plate while not permitting chips whose smallest sectional chip dimension is larger than a predetermined maximum chip dimension, to pass through the filter plate,
wherein:
the at least one filter plate has a thickness of less than 0.3 mm,
the openings include an array of profiled orifices etched through the filter plate, the etched orifice profile being such that the smallest sectional aperture dimension of each orifice is less than 0.3 mm, and such that the sum of the aperture areas of the orifices in the array is at least 18% of the total plate area of the array.
2. A conveyor according to claim 1, wherein at least one of the at least one filter plates is arranged in an upper surface andor in a lower surface of the filter box.
3. A conveyor according to claim 1, wherein the filter plate is retained in a frame for maintaining the filter plate under lateral tension.
4. A conveyor according to claim 1, wherein each of the etched profiled orifices has a straight-through profile, substantially orthogonal to the plane of the filter plate, over at least a portion of the thickness of the filter plate.
5. A conveyor according to claim 1, wherein each of the etched profiled orifices has a flared profile portion, flaring from a waist region of minimum aperture area to one of the filter plate surfaces, over at least a portion of the thickness of the filter plate.
6. A conveyor according to claim 5, wherein the waist region is located in a plane intermediate to the thickness of the filter plate.
7. A conveyor according to claim 6, wherein the plane of the waist region is at the surface of the filter plate which faces outward from the filter box.
8. A conveyor according to claim 6, wherein the plane of the waist region is at the surface of the filter plate which faces inwards into the filter box.
9. A conveyor according to claim 1, wherein the belt further comprises at least one wiping element arranged to wipe across the filter plate as the belt rotates.
10. A conveyor according to claim 1, further comprising backwashing means for inducing a flow of cutting fluid through the profiled orifices in a direction counter to the direction of flow of the cutting fluid through the orifices during filtering.
11. A conveyor according to claim 10, wherein the backwashing means comprises a positive pressure generating means for increasing the pressure at the orifices of cutting fluid within the filter box to be greater than the pressure of cutting fluid outside the filter box.
12. A conveyor according to claim 10, wherein the backwashing means is adapted to induce one or more positive pressure pulses in the cutting fluid within the filter box such that a backwashing of the orifices is achieved without significantly interrupting the flow of cutting fluid in the filtration direction.
13. A method of removing chips from a cutting fluid using a filtering chip conveyor,
the filtering chip conveyor comprising a conveyor tank arranged to retain the cutting fluid containing chips, a continuous conveyor belt at least partly disposed inside the conveyor tank, and a filter box arranged between upper and lower flights of the belt such that upper andor lower surfaces of the filter box are wiped by at least one wiper element arranged on the inside of the continuous conveyor belt, the filter box being provided with a filter plate having a thickness of less than 0.3 mm, the filter plate being arranged to be wiped by the said wiper elements,
the step of providing the filter plate including a step of photo-etching or chemically milling an array of profiled orifices in the filter plate, such that the etched profiled orifices each have a minimum aperture dimension of less than 0.3 mm, and such that the sum of the aperture areas of the orifices in the array is at least 18% of the total plate area of the array.
14. A method according to claim 13, comprising a step of mounting the filter plate to the filter box such that the filter plate is held in tension when the filter plate is wiped by the wiper elements.
15. A conveyor according to claim 1, wherein the etched profiled orifices have a minimum aperture dimension of between 0.1 and 0.2 mm, and the filter plate has a thickness of between 0.1 and 0.2 mm.
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 pharmaceutical composition for transdermal delivery comprising
one or more physiologically active agents;
one or more dermal penetration enhancers; and
a volatile pharmaceutically acceptable carrier comprising a volatile solvent;
and wherein the physiologically active agent and dermal penetration enhancer form an amorphous deposit upon evaporation of the volatile carrier, said amorphous deposit forming a reservoir within the stratum corneum; and
wherein the composition has a release rate profile of physiologically active agent so as to provide a ratio of the maximum concentration (Cmax) to the average concentration (Cavg) for the physiologically active agent over the dosage interval within the range of 1 to 5.
2. (canceled)
3. A pharmaceutical composition according to claim 1 wherein the composition provides a substantially zero order or substantially first order release rate profile of the physiologically active agent over the dosage interval whichever is desirable for the therapeutic effect of the physiologically active agent.
4. The transdermal drug delivery system according to claim 1, wherein the composition provides a zero order release rate profile of the physiologically active agent so as to reduce the ratio of the maximum concentration (Cmax) to the average concentration (Cavg) to a value less than 2 for the physiologically active agent over the dosage interval in order to reduce potential side effects associated with elevated Cmax to Cavg ratios.
5. The transdermal drug delivery system according to claim 1, wherein the composition provides a zero order release rate profile of the physiologically active agent so as to reduce the ratio of the maximum concentration (Cmax) to the average concentration (Cavg) to a value less than 1.5 for the physiologically active agent over the dosage interval in order to reduce potential side effects associated with elevated Cmax to Cavg ratios.
6. The transdermal drug delivery system according to claim 1, wherein the composition provides a first order release rate profile of the physiologically active agent so as to increase the ratio of Cmax to Cavg to a value greater than 1.5 and decrease the time for maximum systemic concentration (tmax) to less than 6 hours for the physiologically active agent over the dosage interval in order to decrease the time to onset of therapeutic response or increase the therapeutic response after a single dose interval.
7. The transdermal drug delivery system according to claim 1, wherein the composition provides a first order release rate profile of the physiologically active agent so as to increase the ratio of Cmax to Cavg to a value greater than 2 and decrease the time for maximum systemic concentration (tmax) to less than 3 hours for the physiologically active agent over the dosage interval in order to decrease the time to onset of therapeutic response or increase the therapeutic response after a single dose interval.
8. The transdermal drug delivery system according to claim 1, wherein the physiologically active agent is a steroid, hormone derivative, opioid analgesic, thrombolytic, antinauseant, anxiolytic, anti-migraine compound, antihypertensive agent, anti-malarial compound, bronchodilator, anti-depressant, anti-Alzheimer’s agent, neuroleptic and antipsychotic agent, anti-Parkinson’s agent, anticholinergic, antiandrogen or anoretic agent.
9. The transdermal drug delivery system according to claim 1, wherein the physiologically active agent is testosterone, oestradiol, ethinyloestradiol, nestorone, levonorgestrel, lacidipine, norethisterone acetate, buspirone, fentanyl, buprenorphine, ropinirole, scopolamine, granisetron, amlodipine, oxybutynin, rivastigmine, rizatriptan, primaquine, fluoxetine, paroxetine, tacrine, N-0923 and mazindol.
10. A pharmaceutical composition according to claim 1 wherein the carrier comprises a hydrofluorocarbon propellant wherein topical application of the composition as an aerosol provides an amorphous deposit on evaporation of the volatile carrier.
11. A pharmaceutical composition according to claim 10 wherein the hydrofluorocarbon propellant is HFC-134a.
12. A pharmaceutical composition according to claim 10 wherein the volatile solvent and propellant provide a single phase solution of the active agent.
13. A pharmaceutical composition according to claim 1 wherein the composition comprises from 0.1% to 10% of physiologically active agent; from 0.1 to 10% by weight of dermal penetration enhancer and from 85% to 99.8% by weight of volatile carrier.
14. A pharmaceutical composition according to claim 10 wherein the hydrofluorocarbon propellant is from 15 to 50% by volume of the total pharmaceutical composition.
15. A pharmaceutical composition according to claim 1 wherein the physiologically active agent component comprise a molecular weight of less than 600 Daltons and a melting point less than 200\xb0 C.
16. A pharmaceutical composition according to claim 1 wherein the penetration enhancer has an organic nature value of from 200 to 400 and an inorganic nature value of from 0 to 200.
17. (canceled)
18. A pharmaceutical composition according to claim 1 wherein the penetration enhancer is a lipophilic liquid having a vapour pressure below 10 mmHg at atmospheric pressure and a temperature of 32\xb0 C. and a molecular weight in the range of from 200 to 400 Daltons.
19. A pharmaceutical composition according to claim 1 wherein the penetration enhancer comprises one or more compounds selected from the groups consisting of fatty acids, fatty acid esters, fatty alcohols, glycols and glycol esters, 1,3-dioxolanes and 1,3-dioxanes, macrocyclic ketones containing at least 12 carbon atoms, oxazolidinones and oxazolidinone derivatives, alkyl-2-(N,N-disubstituted amino)-alkanoate esters, (N,N-disubstituted amino)-alkanol alkanoates, and mixtures thereof, most preferably the dermal penetration enhancer is selected from the list including oleic acid, oleyl alcohol, cyclopentadecanone, sorbitan monooleate, glycerol monooleate, propyle glycol monolaurate, polyethylene glycol monolaurate, 2-n-nonyl 1,3-dioxolane, dodecyl 2-(N,N-dimethylamino)-propionate or its salt derivatives, 2-ethylhexyl 2-ethylhexanoate, isopropyl myristate, dimethyl isosorbide, 4-decyloxazolidinon-2-one, 3-methyl-4-decyloxazolidinon-2-one, and mixtures thereof.
20. A pharmaceutical composition according to claim 1 wherein the solvent comprises ethanol, isopropanol or a mixture thereof.
21. A pharmaceutical composition according to claim 1 wherein the molar ratio of the physiologically active agent compound and the dermal penetration enhancer is from 1:20 to 20:1.
22. A pharmaceutical composition according to claim 1 wherein the composition is contained in a chamber of a spray applicator device comprising a valve for delivering the composition from the chamber, a nozzle for dispersing the composition as an aerosol and means for providing a metered dose of aerosol from the nozzle.
23. (canceled)
24. A method of treatment to provide enhanced percutaneous absorption of a physiologically active substance, the method comprising the step of applying a spray of a pharmaceutical composition according to claim 1 to the skin of a subject to form an amorphous deposit of the active agent and penetrating enhancer upon evaporation of the volatile solvent whereby partitioning of the physiologically active agent from the stratum corneum to the viable epidermis is enhanced.
25. A method of treatment to provide a substantially zero order release rate profile of the physiologically active agent, the method comprising applying a spray of a pharmaceutical composition according to claim 1 to the skin of a subject wherein the potential side effects associated with elevated maximum bloodstream concentrations of the active (Cmax) over the dosage interval are reduced, whilst still maintaining effective average bloodstream concentrations of the active (Cavg).
26. A method of treatment to provide a substantially first order release rate profile of the physiologically active agent the method comprising by applying a spray of a pharmaceutical composition according to claim 1 to the skin of a subject wherein the time to onset of a therapeutic response to the active or an increase in the therapeutic response to the active is achieved by a decrease in the time to maximum concentration of the active in the bloodstream (tmax) and by an increase in the ratio of Cmax to Cavg over the dosage interval.