System and method for optimizing tissue barrier transfer of compounds

• US 6,758,099 B2
• Filed: 07/13/2001
• Issued: 07/06/2004
• 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: Chen, Hongming, Gyory, J. Richard, Lemmo, Anthony V., Cima, Michael J.
• Primary Examiner(s): Weber, Jon P.
• Assistant Examiner(s): LEITH, PATRICIA A
• Application Number:
  US09/904,725
• Publication Number:
  US 20020025509A1
• Time in Patent Office: 1,089 Days
• Field of Search: 435/4, 422/946, 422/948, 210/500.21, 210/513, 73/11.6, 73/12.5, 73/13.7, 73/52, 738/61, 738/610.4, 73/73
• US Class Current: 73/861
• CPC Class Codes: B01L 3/50255 Multi-well filtration
• 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 2500/00 Screening for compounds of potential therapeutic value
• CPC Class Codes: G01N 33/5008 for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
• CPC Class Codes: G01N 33/5044 involving specific cell types
• 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 barrier transfer of a sample, comprising:

first, 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;

then, overlaying the array of the samples with a tissue specimen;

next, securing a 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 the change in concentration of the one or more sample components in each reservoir to determine transfer of said sample components from each sample across the tissue specimen.

2. The method of claim 1, wherein each sample differs from at least one other sample with respect to at least the identity of the active component.

3. The method of claim 1, wherein each sample differs from at least one other sample with respect to at least the identity of the additional components.

4. The method of claim 3, where the additional component is an adhesive.

5. The method of claim 3, where the additional component is a penetration enhancer.

6. The method of claim 3, where the additional component is an solvent.

7. The method of claim 1, wherein each sample differs from at least one other sample with respect to at least the ratio of the active component to the additional component.

8. The method of claim 1, wherein each sample contains less than 100 nanograms of active component.

9. The method of claim 1, wherein each sample has a total volume of about 1-200 μ

l.

10. A method of analyzing tissue barrier flux of a sample, comprising the steps of:

first, preparing an array of 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;

then, overlaying the array of samples with a tissue specimen;

next, securing a 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 as a function of time to determine flux of the component-in-common from each sample across the tissue specimen.

11. The method of claim 10, wherein each sample differs from at least one other sample with respect to at least the identity of the active component.

12. The method of claim 10, wherein each sample differs from at least one other sample with respect to at least the identity of the additional components.

13. The method of claim 12, where the additional component is an adhesive.

14. The method of claim 12, where the additional component is a penetration enhancer.

15. The method of claim 12, where the additional component is a solvent.

16. The method of claim 10, wherein each sample differs from at least one other sample with respect to at least the ratio of the active component to the additional component.

17. The method of claim 10, wherein each sample contains less than 100 nanograms of active component.

18. The method of claim 10, wherein each sample has a total volume of about 1-200 μ

l.

19. The method of claim 10, further comprising, periodically mesuring the concentration of the at least one component in each reservoir to determine flux of said at least one component from said sample across the tissue specimen into sad reservoir medium, where said measuring occurs while said reservoir plate is secured to said tissue specimen.