System and method for optimizing tissue barrier transfer of compounds

• US 7,172,859 B2
• Filed: 02/20/2003
• Issued: 02/06/2007
• Est. Priority Date: 07/14/2000
• Status: Expired due to Fees

• Current Assignee: TransForm Pharmaceuticals, Inc. (Johnson & Johnson)
• Original Assignee: TransForm Pharmaceuticals, Inc. (Johnson & Johnson)
• Inventors: Cima, Michael J., Gyory, J. Richard, Chen, Hongming
• Primary Examiner(s): Beisner; William H.
• Application Number:
  US10/371,372
• Publication Number:
  US 20030170610A1
• Time in Patent Office: 1,447 Days
• Field of Search: 435/4, 435/33, 435/287.1, 435/287.9, 435/288.4, 435/297.1, 435/297.2, 435/297.5, 73/38, 73/73, 738/610.4, 738/61
• US Class Current: 435/4
• CPC Class Codes: G01N 13/00 Investigating surface or boundary effects, e.g. wetting power; Investigating diffusion effects; Analysing materials by determining surface, boundary, or diffusion effects scanning-probe techniques or apparatus G01Q
• CPC Class Codes: G01N 33/5088 of vertebrates

Abstract

The present invention relates to high-throughput systems and methods to prepare a large number of component combinations, at varying concentrations and identities, at the same time, and high-throughput methods to test tissue barrier transfer, such as transdermal transfer, of components in each combination. The methods of the present invention allow determination of the effects of inactive components, such as solvents, excipients, enhancers, adhesives and additives, on tissue barrier transfer of active components, such as pharmaceuticals. The invention thus encompasses the high-throughput testing of pharmaceutical compositions or formulations in order to determine the overall optimal composition or formulation for improved tissue transport, such as transdermal transport.

Claims

1. A method of measuring tissue baffler transfer of a sample, comprising:

preparing an array of samples, each sample comprising an active component and at least one additional component, wherein each sample differs from at least one other sample with respect to at least one of the identity of the active component, the identity of the additional components, the ratio of the active component to the additional component, or the physical state of the active component;

loading said array of samples onto a lower substrate plate that supports said samples;

overlaying the array of samples with a tissue specimen;

securing an upper reservoir plate to a side of the tissue specimen opposite the array of samples, the reservoir plate having an array of reservoirs corresponding to the array of samples;

filling the array of reservoirs with a reservoir medium; and

measuring concentration of one or more sample components in each reservoir of said upper reservoir plate to determine transfer of said sample components from each sample across the tissue specimen;

wherein;

(a) each sample in the array of samples is a solid source sample or a liquid source sample;

(b) the active component is a pharmaceutical, a dietary supplement, a nutraceutical or an alternative medicine;

(c) the additional component is an excipient, a solvent, an adhesive, an enhancer, an additive, or a combination thereof;

(d) the additional component is an adhesive selected from a polyisobutylene, a silicone, or an acrylic adhesive;

(e) the method further comprises the step of detecting an inhomogeneous segment; and

correcting for an inhomogeneous segment, wherein the correcting step comprises any of;

removing the inhomogeneous segment;

ignoring concentration measurement associated with the inhomogeneous segment;

adjusting concentration measurements to correct for the inhomogeneous segment;

or repairing the inhomogeneous segment;

or

(f) wherein the tissue specimen is skin tissue.

2. The method according to claim 1, wherein each sample in the array of samples is a solid source sample or a liquid source sample.

3. The method according to claim 1, wherein the active component is a pharmaceutical, a dietary supplement, a nutraceutical or an alternative medicine.

4. The method according to claim 1, wherein the additional component is an excipient, a solvent, an adhesive, an enhancer, an additive, or a combination thereof.

5. The method according to claim 1, wherein the additional component is an adhesive selected from a polyisobutylene, a silicone, or an acrylic adhesive.

6. The method according to claim 1, wherein the method further comprises the step of detecting an inhomogeneous segment;

and correcting for an inhomogeneous segment, wherein the correcting step comprises any of;

removing the inhomogeneous segment;

ignoring concentration measurement associated with the inhomogeneous segment;

adjusting concentration measurements to correct for the inhomogeneous segment;

or repairing the inhomogeneous segment.

7. The method according to claim 1, wherein the tissue specimen is skin tissue.

8. A method of analyzing tissue barrier flux of a sample, comprising:

preparing an array of samples, each sample comprising an active component, a component-in-common and at least one additional component, wherein each sample differs from at least one other sample with respect to at least one of;

the identity of the additional components, the ratio of the component-in-common to the additional component, or the physical state of the component-in-common;

loading said array of samples onto a substrate plate that supports said samples;

overlaying the array of samples with a tissue specimen;

securing an upper reservoir plate to a side of the tissue specimen opposite the array of samples, the reservoir plate having an array of reservoirs corresponding to the array of samples;

filling the array of reservoirs with a reservoir medium; and

measuring concentration of the component-in-common in each reservoir of said upper reservoir plate as a function of time to determine flux of the component-in-common from each sample across the tissue specimen;

wherein;

(a) each sample in the array of samples is a solid source sample or a liquid source sample;

(b) the active component is a pharmaceutical, a dietary supplement, a nutraceutical or an alternative medicine;

(c) the additional component is an excipient, a solvent, an adhesive, an enhancer, an additive, or a combination thereof;

(d) the additional component is an adhesive selected from a polyisobutylene, a silicone, or an acrylic adhesive;

(e) the method further comprises the step of detecting an inhomogeneous segment; and

correcting for an inhomogeneous segment, wherein the correcting step comprises any of;

removing the inhomogeneous segment;

ignoring concentration measurement associated with the inhomogeneous segment;

adjusting concentration measurements to correct for the inhomogeneous segment;

or repairing the inhomogeneous segment;

or

(f) wherein the tissue specimen is skin tissue.

9. The method according to claim 8, wherein each sample in the array of samples is a solid source sample or a liquid source sample.

10. The method according to claim 8, wherein the active component is a pharmaceutical, a dietary supplement, a nutraceutical or an alternative medicine.

11. The method according to claim 8, wherein the additional component is an excipient, a solvent, an adhesive, an enhancer, an additive, or a combination thereof.

12. The method according to claim 8, wherein the additional component is an adhesive selected from a polyisobutylene, a silicone, or an acrylic adhesive.

13. The method according to claim 8, wherein the method further comprises the step of detecting an inhomogeneous segment;

and correcting for an inhomogeneous segment, wherein the correcting step comprises any of;

removing the inhomogeneous segment;

ignoring concentration measurement associated with the inhomogeneous segment;

adjusting concentration measurements to correct for the inhomogeneous segment;

or repairing the inhomogeneous segment.

14. The method according to claim 8, wherein the tissue specimen is skin tissue.

15. A method of determining tissue barrier flux of a component, comprising:

preparing an array of solid source samples, each sample comprising a component-in-common and at least one additional component, wherein each sample differs from at least one other sample with respect to at least one of;

the identity of the additional components, the ratio of the component-in-common to the additional component, or the physical state of the component-in-common;

loading said array of samples onto a substrate plate that supports said samples;

overlaying the array of samples with a tissue specimen; and

determining flux of the component-in-common from a first sample in said array of samples across a tissue specimen.

16. The method according to claim 15, wherein the component-in-common is a pharmaceutical, a dietary supplement, a nutraceutical or an alternative medicine.

17. The method according to claim 15, wherein the additional component is an excipient, a solvent, an adhesive, an enhancer, an additive, or a combination thereof.

18. The method according to claim 15, wherein the additional component is an adhesive selected from a polyisobutylene, a silicone, or an acrylic adhesive.

19. The method according to claim 15, wherein the method further comprises the step of detecting an inhomogeneous segment;

and correcting for an inhomogeneous segment, wherein the correcting step comprises any of;

removing the inhomogeneous segment;

ignoring concentration measurement associated with the inhomogeneous segment;

adjusting concentration measurements to correct for the inhomogeneous segment;

or repairing the inhomogeneous segment.

20. The method according to claim 15, wherein the tissue specimen is skin tissue.

21. A method of determining optimal transdermal compositions or formulations, comprising:

preparing an array of samples, each sample comprising an active component and at least one additional component, wherein each sample differs from at least one other sample with respect to at least one of;

the identity of the active component, the identity of the additional components, the ratio of the active component to the additional component, or the physical state of the active component;

loading said array of samples onto a substrate plate that supports said samples;

overlaying the array of samples with a tissue specimen;

securing a reservoir plate an upper reservoir plate to a side of the tissue specimen opposite the array of samples, the reservoir plate having an array of reservoirs corresponding to the array of samples;

filling the array of reservoirs with a reservoir medium; and

measuring concentration of the active component in each reservoir of said upper reservoir plate as a function of time to determine flux of the active component from each sample across the tissue specimen; and

determining flux of the active component from each sample in said array of samples across the skin tissue to determine an optimal transdermal formulation.

22. The method according to claim 21, wherein each sample in the array of samples is a solid source sample or a liquid source sample.

23. The method according to claim 21, wherein the active component is a pharmaceutical, a dietary supplement, a nutraceutical or an alternative medicine.

24. The method according to claim 21, wherein the additional component is an excipient, a solvent, an adhesive, an enhancer, an additive, or a combination thereof.

25. The method according to claim 21, wherein the additional component is an adhesive selected from a polyisobutylene, a silicone, or an acrylic adhesive.

26. The method according to claim 21, wherein the method further comprises the step of detecting an inhomogeneous segment in said skin tissue and correcting for an inhomogeneous segment, wherein the correcting step comprises any of:

removing the inhomogeneous segment;

ignoring concentration measurement associated with the inhomogeneous segment;

adjusting concentration measurements to correct for the inhomogeneous segment;

or repairing the inhomogeneous segment.

27. A method of determining optimal transdermal compositions or formulations, comprising:

preparing an array of samples, each sample comprising an component-in-common and at least one additional component, wherein each sample differs from at least one other sample with respect to at least one of;

the identity of the additional components, the ratio of the component-in-common to the additional component, or the physical state of the component-in-common;

loading said array of samples onto a substrate plate that supports said samples;

overlaying the array of samples with a tissue specimen;

securing an upper reservoir plate to a side of the tissue specimen opposite the array of samples, the reservoir plate having an array of reservoirs corresponding to the array of samples;

filling the array of reservoirs with a reservoir medium; and

measuring concentration of the component-in-common in each reservoir of said upper reservoir plate as a function of time to determine flux of the component-in-common from each sample across the tissue specimen, and determining flux of the component-in-common from each sample in said array of samples across the skin tissue to determine an optimal transdermal formulation.

28. The method according to claim 27, wherein each sample in the array of samples is a solid source sample or a liquid source sample.

29. The method according to claim 27, wherein the component-in-common is a pharmaceutical, a dietary supplement, a nutraceutical or an alternative medicine.

30. The method according to claim 27, wherein the additional component is an excipient, a solvent, an adhesive, an enhancer, an additive, or a combination thereof.

31. The method according to claim 27, wherein the additional component is an adhesive selected from a polyisobutylene, a silicone, or an acrylic adhesive.

32. The method according to claim 27, wherein the method further comprises the step of detecting an inhomogeneous segment in said skin tissue and correcting for an inhomogeneous segment, wherein the correcting step comprises any of:

removing the inhomogeneous segment;

ignoring concentration measurement associated with the inhomogeneous segment;

adjusting concentration measurements to correct for the inhomogeneous segment;

or repairing the inhomogeneous segment.