1. An oral dosage form comprising:
(a) an effective amount of an alkalizing agent; and
(b) multiparticulates wherein said multiparticulates comprise (i) about 20% to about 75% azithromycin, and (ii) about 25% to about 80% of a glyceride which comprises glyceryl monobehenate, glyceryl dibehenate, glyceryl tribehenate or a mixture thereof; and (iii) a poloxamer.
2. An oral dosage form of claim 1 wherein the poloxamer comprises poloxamer 407.
3. An oral dosage form of claim 1 wherein the alkalizing agent comprises a bicarbonate, a phosphate, a metal hydroxide, a metal oxide or a combination thereof.
4. An oral dosage form of claim 3 wherein the alkalizing agent comprises tribasic sodium phosphate and magnesium hydroxide.
5. An oral dosage form of claim 3 further comprising about 250 mgA to about 7 gA of azithromycin.
6. An oral dosage form of claim 5 further comprising about 1.5 gA to about 4 gA of azithromycin.
7. An oral dosage form of claim 5 further comprising 1.8 to 2.2 gA of azithromycin.
8. An azithromycin oral dosage form, comprising:
(a) at least about 200 mg of tribasic sodium phosphate; and
(b) multiparticulates, wherein said multiparticulates comprise (i) azithromycin, (ii) a mixture of glyceryl monobehenate, glyceryl dibehenate and glyceryl tribehenate, and (iii) poloxamer 407, and wherein said dosage form contains about 1.5 gA to about 4 gA of azithromycin.
9. An oral dosage form of claim 8, further comprising at least about 100 mg of magnesium oxide.
10. An oral dosage form of claim 8, comprising:
(a) 300 mg to 400 mg of tribasic sodium phosphate;
(b) 200 mg to 300 mg of magnesium hydroxide; and
(c) multiparticulates, wherein said multiparticulates comprise (i) azithromycin, (ii) a mixture of glyceryl monobehenate, glyceryl dibehenate and glyceryl tribehenate, and (iii) poloxamer 407,
and wherein said dosage form contains about 1.5 gA to about 4 gA of azithromycin.
11. An oral dosage form of claim 8 further comprising 1.8 to 2.2 gA of azithromycin.
12. An oral dosage form of claim 11 wherein said azithromycin is azithromycin dihydrate.
13. An oral dosage form of claim 1 wherein said azithromycin is azithromycin dihydrate.
14. An oral dosage form of claim 3 wherein said azithromycin is at least 70 wt % crystalline.
15. An oral dosage form of claim 3 wherein said oral dosage form is a powder for oral suspension, a unit dose packet, an oral suspension, a tablet or a capsule.
16. A method for reducing the frequency of gastrointestinal side effects, associated with administering azithromycin to a mammal, comprising contiguously administering oral dosage form of claim 1 to said mammal wherein the frequency of gastrointestinal side effects is reduced as compared to the frequency experienced when administering an equal dose of azithromycin without said alkalizing agent.
17. A method of claim 16 wherein said mammal is a human.
18. A method of claim 17 further comprising administering between about 250 mgA and about 7 gA of azithromycin to said human.
19. A method of claim 18 wherein the azithromycin is administered in a single dose.
20. A method of claim 19 further comprising administering between about 1.5 and about 4 gA of azithromycin.
21. A method of claim 19 further comprising administering between about 1.5 and about 3 gA of azithromycin.
22. A method of claim 19 further comprising administering between 1.8 and 2.2 gA of azithromycin to said human in a single dose.
23. A method of claim 17 further comprising administering between 30 mgAkg and 90 mgAkg of azithromycin to a human, wherein said human is a child weighing 30 kg or less.
24. A method of claim 23 wherein the azithromycin is administered in a single dose.
25. A method of claim 24 further comprising administering between 45 mgAkg and 75 mgAkg of azithromycin to a child weighing 30 kg or less.
26. A method of claim 24 further comprising administering about 60 mgAkg of azithromycin to a child weighing 30 kg or less.
27. A method of claim 16 wherein the alkalizing agent further comprises a bicarbonate, a phosphate, a metal hydroxide, a metal oxide, or a combination thereof.
28. A method of claim 27 wherein the alkalizing agent comprises tribasic sodium phosphate and magnesium hydroxide.
29. A method of claim 27 wherein said azithromycin comprises an immediate release form of azithromycin.
30. A method of claim 27 wherein said azithromycin comprises a sustained release form of azithromycin.
31. A method of claim 27 wherein said azithromycin comprises azithromycin multiparticulates.
32. A method of claim 31 wherein said azithromycin multiparticulates comprise:
(a) azithromycin; and
(b) a pharmaceutically acceptable carrier.
33. A method of treating a bacterial or protozoal infection in a mammal in need thereof comprising administering to said mammal a single dose of an oral dosage form of claim 1.
34. A method of claim 33 wherein said mammal is a human.
35. A method of claim 34 further comprising administering between about 250 mgA and about 7 gA of azithromycin to said human.
36. A method of claim 35 wherein the azithromycin is administered in a single dose.
37. A method of claim 36 further comprising administering between about 1.5 and about 4 gA of azithromycin to said human.
38. A method of claim 36 further comprising administering between about 1.5 and about 3 gA of azithromycin to said human.
39. A method of claim 36 further comprising administering 1.8 gA to 2.2 gA of azithromycin to said human.
40. A method of claim 34 further comprising administering between 30 mgAkg and 90 mgAkg of azithromycin to said human, wherein said human is a child weighing 30 kg or less.
41. A method of claim 34 wherein the azithromycin is administered in a single dose.
42. A method of claim 41 further comprising administering between 45 mgAkg and 75 mgAkg of azithromycin to a child weighing 30 kg or less.
43. A method of claim 41 further comprising administering 60 mgAkg of azithromycin to a child weighing 30 kg or less.
44. A method of claim 33 wherein the alkalizing agent comprises a bicarbonate, a phosphate, a metal hydroxide, a metal oxide, or a combination thereof.
45. A method of claim 44 wherein the alkalizing agent comprises tribasic sodium phosphate.
46. A method of claim 45 wherein the alkalizing agent further comprises magnesium hydroxide.
47. A method of claim 44 wherein said azithromycin comprises an immediate release form of azithromycin.
48. A method of claim 44 wherein said azithromycin comprises a sustained release form of azithromycin.
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 verifying a circuit design, the method comprising:
automatically analyzing a description of the circuit design to determine a receiving register receiving a clock domain crossing signal on at least one input;
automatically generating a metastability effects generator for injecting metastability effects onto an output of said receiving register based on the analysis; and
controlling said metastability effects generator to inject metastability effects during a simulation test.
2. The method of claim 1, further comprising automatically identifying a transmit clock domain associated with a transmit clock and a receive clock domain associated with a receive clock, said receive clock clocking said receiving register.
3. The method of claim 2, further comprising automatically identifying a clock domain crossing signal that crosses from said transmit clock domain to said receive clock domain and is applied as an input to said receiving register.
4. The method of claim 3, further comprising associating said metastability effects generator with said transmit clock and said receive clock.
5. The method of claim 4, further comprising associating said metastability effects generator with an input of a transmitting register in said transmit domain, said clock domain crossing signal and said output of said receiving register.
6. The method of claim 5, further comprising causing said metastability effects generator to force metastability effects onto said output of said receiving register when said transmit clock and said receive clock are aligned and said clock domain crossing signal is changing value at said input of said receiving register.
7. The method of claim 6 further comprising specifying a window of simulated time used to determine when said transmit clock and said receive clock are aligned.
8. The method of claim 7, wherein the duration of said window is selectable.
9. The method of claim 6 wherein said metastability effects generator is configured to pseudo-randomly force metastability effects.
10. The method of claim 9 wherein said metastability effects generator is configured to generate identical metastability effects when simulation of said simulation test is repeated.
11. The method of claim 6 wherein said metastability effects generator is configured to force metastability effects by inverting the logic value of said output of said receiving register.
12. The method of claim 6 wherein said metastability effects generator forces metastability effects after a delay following an active edge of said receive clock.
13. The method of claim 6 wherein said metastability effects generator forces metastability effects in accordance with a pre-determined algorithm.
14. The method of claim 5 wherein a separate metastability effects generator is associated with each individual bit of a multi-bit register in said circuit under verification.
15. The method of claim 5, further comprising automatically creating a netlist for said input to said transmitting register, said netlist used to generate a logic expression that determines, during said simulation test, when said clock domain crossing signal changes value.
16. The method of claim 1 further comprising selectively disabling at least one metastability effects generator prior to executing said simulation test.
17. The method of claim 1 further comprising using an assertion to detect incorrect behavior of said circuit design during said simulation test.
18. The method of claim 17 wherein said assertion is automatically generated.
19. The method of claim 1, wherein code for the metastability effects generator is automatically determined and stored in a separate file from a file storing the circuit description.
20. The method of claim 1, wherein code for the metastability effects generator is not found in the description of the circuit design before the analyzing of the description of the circuit design.
21. A method for verifying a circuit design, said circuit design containing a receiving register receiving a clock domain crossing signal on at least one input, the method comprising:
automatically generating a metastability effects generator for injecting metastability effects onto an output of said receiving register;
controlling said metastability effects generator to inject metastability effects during a simulation test;
generating a coverage report at the conclusion of said simulation test, wherein said coverage report comprises at least one of the following statistics acquired during simulation of said simulation test:
number of times a clock in a transmit clock domain is aligned with a clock in a receive clock domain,
number of times an input of a register receiving a clock domain crossing signal is changing when a clock in a transmit clock domain is aligned with a clock in a receive clock domain, and
number of times metastability effects are forced onto the output of a register receiving a clock domain crossing signal.
22. The method of claim 21 wherein said coverage report comprises at least one of the following statistics acquired during simulation of said simulation test:
when during simulation was a clock in a transmit clock domain aligned with a clock in a receive clock domain,
when during simulation was an input of a register receiving a clock domain crossing signal changing when a clock in a transmit clock domain was aligned with a clock in a receive clock domain, and
when during simulation were metastability effects forced onto the output of a register receiving a clock domain crossing signal.
23. A method of verifying a circuit design comprising:
automatically identifying a transmit clock domain associated with a transmit clock and a receive clock domain associated with a receive clock;
automatically identifying a clock domain crossing signal that originates at an output of a transmitting register in said transmit clock domain and is applied as an input to a receiving register in said receive clock domain by analyzing the circuit design;
automatically associating a metastability effects generator with said transmit clock and said receive clock and an input and an output of said receiving register based on the analysis; and
causing said metastability effects generator to inject metastability effects onto an output of said receiving register when said transmit clock and said receive clock are aligned and a signal on said input of said receiving register is changing during a simulation test.
24. The method of claim 23 further comprising specifying a window of simulated time used to determine when said transmit clock and said receive clock are aligned.
25. The method of claim 24 wherein the duration of said window is selectable.
26. The method of claim 23 wherein said metastability effects generator is configured to pseudo-randomly force metastability effects.
27. The method of claim 26 wherein said metastability effects generator is configured to generate identical metastability effects when simulation of said simulation test is repeated.
28. The method of claim 23 wherein said metastability effects generator is configured to force metastability effects by inverting the logic value of said output of said receiving register.
29. The method of claim 23 further comprising creating a logic expression that determines, during simulation of said simulation test, when said clock domain crossing signal changes value.
30. The method of claim 23 further comprising selectively disabling at least one metastability effects generator prior to executing said simulation test.
31. The method of claim 23 further comprising selectively removing at least one metastability effects generator prior to executing said simulation test.
32. The method of claim 23 wherein a separate metastability effects generator is associated with each individual bit of a multi-bit register in said circuit under verification.
33. The method of claim 23 further comprising using an assertion to detect incorrect behavior of said circuit design during said simulation test.
34. The method of claim 33 wherein said assertion is automatically generated.
35. The method of claim 23 further comprising generating a coverage report at the conclusion of said simulation test.
36. A system for simulating a circuit under verification by executing a simulation test, said circuit under verification having a transmit clock domain and a receive clock domain, wherein clock edges in said transmit clock domain occur asynchronously with respect to clock edges in said receive clock domain, said system comprising:
a first detector for monitoring a transmit clock in said transmit clock domain and a receive clock in said receive clock domain, said first detector adapted to detect when said clocks are aligned and to generate a signal in response to said detection;
a receiving register in said receive clock domain having an input coupled to an output of a transmitting register in said transmit clock domain;
a second detector adapted to detect a change in logic value on said input and to generate a signal in response thereto;
a metastability injector, in response to a signal generated by said first detector and a signal generated by said second detector, adapted to force the effects of metastability onto an output of said receiving register, the metastability injector automatically generated based on an analysis of the circuit under verification; and
means for verifying correct simulated operation of said circuit under verification.
37. The system of claim 36 wherein said metastability injector is configured to pseudo-randomly force the effects of metastability onto said output of said receiving register when said transmit clock and said receive clock are aligned and said input of said receiving register changes logic value.
38. The system of claim 36 wherein said first detector is configured to determine that said clocks are aligned when the active edge of said transmit clock occurs during a window of simulated time defined relative to the active edge of said receive clock.
39. The system of claim 38 wherein the width of said window is selectable.
40. The system of claim 36 further comprising a user interface adapted to selectively disable at least one of said metastability injectors simulating said circuit under verification.
41. The system of claim 36 wherein said circuit under verification contains at least one multi-bit register and a separate metastability injector is associated with each individual bit of said multi-bit register.
42. The system of claim 36 wherein said verifying means includes a user interface for presentation of a coverage report in response to said simulating of said circuit under verification.
43. A system for simulating a circuit under verification by executing a simulation test, said circuit under verification having a transmit clock domain and a receive clock domain, wherein clock edges in said transmit clock domain occur asynchronously with respect to clock edges in said receive clock domain, said system comprising:
a first detector for monitoring a transmit clock in said transmit clock domain and a receive clock in said receive clock domain, said first detector adapted to detect when said clocks are aligned and to generate a signal in response to said detection;
a receiving register in said receive clock domain having an input coupled to an output of a transmitting register in said transmit clock domain;
a second detector adapted to detect a change in logic value on said input and to generate a signal in response thereto;
a metastability injector, in response to a signal generated by said first detector and a signal generated by said second detector, adapted to force the effects of metastability onto an output of said receiving register; and
means for verifying correct simulated operation of said circuit under verification, wherein said first detector further includes:
means for recording the simulated time of an active edge of said receive clock and an active edge of said transmit clock; and
means for determining if said active edge of said transmit clock occurred during a window of simulated time defined relative to said active edge of said receive clock.
44. The system of claim 43 further comprising:
means for selecting the width of said window of simulated time.
45. A method for verifying a circuit design comprising:
automatically creating a netlist of a portion of said circuit design;
automatically identifying a clock domain crossing signal from said netlist based on an analysis of the circuit design;
automatically generating a metastability generator circuit for injecting the effects of metastability onto a node of said circuit during simulation based on the analysis;
executing a simulation test to verify said circuit design operates correctly; and
re-simulating said simulation test with said metastability generator enabled to inject metastability effects to verify said circuit design operates correctly when subjected to metastability effects.
46. A method for verifying a circuit design comprising:
automatically creating a netlist of a portion of said circuit design;
automatically identifying a clock domain crossing signal from said netlist;
automatically generating a metastability generator circuit for injecting the effects of metastability onto a node of said circuit during simulation;
executing a simulation test to verify said circuit design operates correctly; and
re-simulating said simulation test with said metastability generator enabled to inject metastability effects to said circuit design operates correctly when subjected to metastability effects;
measuring the number of times a transmit clock in a transmit domain is aligned with a receive clock in a receive clock domain during said re-simulating step; and
measuring the number of times a metastability effect is forced during said re-simulating step.
47. The method of claim 46 further comprising specifying a window of simulated time relative to an active edge of said receive clock to define when said receive clock and said transmit clock are aligned.
48. The method of claim 46 further comprising acquiring a plurality of statistics relating to the injection of the metastability effects and generating a coverage report.
49. The method of claim 46 further comprising using an assertion to automatically detect incorrect behavior of said circuit design related to the injection of metastability effects during said re-simulating step.