PHARMACEUTICAL FORMULATIONS FOR IONTOPHORETIC TETRACYCLINE ANTIBIOTIC DELIVERY
Pharmaceutical formulations suitable for iontophoresis that provide enhanced iontophoretic delivery of tetracycline antibiotic to at least one target tissue are described and methods for administering tetracycline antibiotic via iontophoresis.
1 . A formulation suitable for iontophoresis comprising at least one tetracycline antibiotic at an ionic strength of at least about 0.05M.
2 . The formulation of claim 1 wherein the tetracycline antibiotic is selected from tetracycline, chlortetracycline, oxytetracycline, demecloycline, doxycycline, lymecyline, meclocyline, methacycline, minocyline, rolitetracycline and tigecycline.
3 . The formulation of claim 1 wherein the tetracycline antibiotic is selected from tetracycline and doxycycline.
4 . The formulation of claim 1 wherein the formulation further comprises a viscosity modulating agent selected from cellulosic polymers and derivatives thereof, crosslinked acrylic acid polymers, hydrophilic polymers, gums, sodium alginate; gelatin and any combination thereof.
5 . A formulation suitable for iontophoresis comprising tetracycline at an ionic strength of at least about 0.1M.
6 . The formulation of claim 5 wherein the ionic strength is at least about 0.25M.
7 . The formulation of claim 6 wherein the iontophoresis is cathodal and performed at a pH of at least about 7.5.
8 . The formulation of claim 7 wherein the pH is about 9.
9 . The formulation of claim 6 wherein the iontophoresis is anodal and performed at a pH of less than about 4.
10 . The formulation of claim 9 wherein the formulation comprises a viscosity modulating agent selected from cellulosic polymers and derivatives thereof, crosslinked acrylic acid polymers, hydrophilic polymers, gums, sodium alginate; gelatin and any combination thereof.
11 . A formulation suitable for cathodal iontophoresis comprising tetracycline at a pH of at least about 7.5.
12 . The formulation of claim 11 wherein the pH is about 9.
13 . The formulation of claim 12 wherein the formulation comprises a viscosity modulating agent selected from cellulosic polymers and derivatives thereof, crosslinked acrylic acid polymers, hydrophilic polymers, gums, alginate; gelatin and any combination thereof.
14 . A formulation suitable for anodal iontophoresis comprising tetracycline at a pH of less than about 4.
15 . The formulation of claim 14 wherein the formulation comprises a viscosity modulating agent selected from cellulosic polymers and derivatives thereof, crosslinked acrylic acid polymers, hydrophilic polymers, gums, alginate; gelatin and any combination thereof.
16 . A method for administering tetracycline to a patient comprising iontophoretically administering to the body surface of a patient in need thereof, the formulation of claim 1 .
17 . The method of claim 16 wherein a current density of at least about 0.02 mA/cm 2 is applied.
18 . The method of claim 17 wherein the current density is at least 0.1 mA/cm 2 .
19 . The method of claim 16 wherein the tetracycline is administered at a flux of at least about 5 μg/cm 2 per hour.
20 . The method of claim 19 wherein the flux is at least about 10 μg/cm 2 per hour.
21 . An iontophoretic device having micro-needles formed on a contacting surface comprising a formulation according to claim 1 .
22 . A method for delivering tetracycline antibiotic to a treatment site underlying the skin of an individual, the method comprising: 1) applying a plurality of micro-needles to the skin to penetrate the skin; and electrokinetically driving the tetracycline antibiotic at an ionic strength of at least about 0.05M and an electrical carrier therefore through pores in the skin formed by the micro-needles and into the treatment site.
23 . A method of claim 22 wherein the tetracycline antibiotic is selected from tetracycline, chlortetracycline, oxytetracycline, demecloycline, doxycycline, lymecyline, meclocyline, methacycline, minocyline, rolitetracycline and tigecycline.
24 . The method of treating acne comprising iontophoretically administering to the body surface of a patient in need thereof, the formulation of claim 1 .
25 . A formulation of claim 1 free of dermal penetration enhancer which is selected from the group consisting of 1-alkylazacyloheptan-2-one, said alkyl having from 8 to 16 carbon atoms, and a cis-olefin of the formula CH 3 (CH 2 ) x CH═CH(CH 2 ) y R 3 where R 3 is CH 2 OH, CH 2 NH 2 or COR 4 , and R 4 is OH or (C 1 -C 4 )alkoxy, x and y are each an integer from 3-13 and the sum of x and y is from 10 to 16.