Tetracycline metal complex in a solid dosage form

1 . A solid dosage form comprising a metal complex of a compound of Formula (I), for pharmaceutical administration,

wherein

R 1 =Cl, N(CH 3 ) 2 , or H;

R 2 =CH 3 , H, or CH 2 ═;

R 3 =CH 3 , H, OH, or absent; and

R 4 =OH or H,

with the proviso that if R 2 is CH 3 and R 3 is H, then R 4 is not OH.

2 . The solid dosage form of claim 1 , wherein said metal complex is selected from the group consisting of a calcium complex, a magnesium complex, a sodium complex, a zinc complex, an aluminum complex, an iron complex, a copper complex and mixtures thereof.

3 . The solid dosage form of claim 2 , wherein said metal complex is a calcium complex.

4 . The solid dosage form of claim 2 , wherein the compound of Formula (I) is selected from the group consisting of tetracycline, chlortetracycline, oxytetracycline, demeclocycline, minocycline, methacycline, lymecycline and a physiologically acceptable salt thereof.

5 . The solid dosage form of claim 1 , wherein the compound of the complex of Formula (I) has a release profile that is immediate, controlled, or sustained.

6 . The solid dosage form of claim 1 , wherein R 1 =N(CH 3 ) 2 , R 2 =H, R 3 =H, and R 4 =H.

7 . The solid dosage form of claim 1 , wherein said pharmaceutical dosage form is selected from the group consisting of powders, granules, tablets, coated tablets, gelatin filled capsules, pellets, and chewable tablets.

8 . A process for making a dry granulation of a metal complex of a compound of Formula (I),

wherein

R 1 =Cl, N(CH 3 ) 2 , or H;

R 2 =CH 3 , H, or CH 2 ═;

R 3 =CH 3 , H, OH, or absent; and

R 4 =OH or H,

with the proviso that if R 2 is CH 3 and R 3 is H, then R 4 is not OH, in a solid dosage form, said process comprising the steps of:

(i) providing an aqueous solution of the compound of Formula (I) or a physiologically acceptable salt thereof, where the compound is partially or completely solubilized;

(ii) admixing a metal salt with said aqueous solution,

(iii) admixing a base to increase the pH of said aqueous solution, whereby a suspension of a metal complex of the compound of Formula (I) is formed after steps (ii) and (iii); and

(iv) drying said suspension, thereby forming a dry granulation of the metal complex of the compound of Formula (I).

9 . The process of claim 8 , wherein said suspension of the metal complex of the compound of Formula (I) provided in step (iii) has a pH range of about 2 to about 14.

10 . The process of claim 8 , wherein said metal salt is selected from the group consisting of calcium salts, magnesium salts, sodium salts, zinc salts, and mixtures thereof.

11 . The process of claim 8 , wherein said metal salt is calcium chloride.

12 . The process of claim 8 , wherein said base is selected from the group consisting of sodium hydroxide, triethanolamine, and mixtures thereof.

13 . The process of claim 8 , wherein said granulation has a moisture level of less than about 10 wt. %.

14 . The process of claim 8 , further comprising the step of admixing one or more pharmaceutically acceptable-excipients, prior to said drying step.

15 . The process of claim 8 , further comprising the step of admixing one or more pharmaceutically acceptable-excipients, after forming said granulation.

16 . The process of claim 8 , wherein the compound of Formula (I) is selected from the group consisting of tetracycline, chlortetracycline, oxytetracycline, demeclocycline, minocycline, methacycline, lymecycline and a physiologically acceptable salt thereof.

17 . The process of claim 8 , further comprising the step of:

(a) compressing said dry granulation, thereby forming tablets; or

(b) filling gelatin capsules with said dry granulation.

18 . The process of claim 8 , wherein the physiologically acceptable salt of the compound of Formula (I) is selected from the group consisting of a hyclate, monohydrate, carrageenate, hydrochloride, phosphate, and mixtures thereof.

19 . A pharmaceutical solid dosage form of the metal complex of the compound of Formula (I), made by the process of claim 8 .

20 . A method of treating bacterial infections and ailments caused by bacteria and microorganisms comprising the step of:

administering to a host in need thereof, an effective amount of a solid dosage form comprising a metal complex of a compound of Formula (I) for pharmaceutical administration,

wherein

R 1 =Cl, N(CH 3 ) 2 , or H;

R 2 =CH 3 , H, OH, or CH 2 ═;

R 3 =CH 3 , H, OH, or absent; and

R 4 =OH or H,

with the proviso that if R 2 is CH 3 and R 3 is H, then R 4 is not OH,

for an effective period of time.