Stable pharmaceutical composition

• US 4,857,552 A
• Filed: 06/08/1988
• Issued: 08/15/1989
• Est. Priority Date: 06/08/1988
• Status: Expired due to Fees

• Current Assignee: BOC Health Care (Becton, Dickinson & Co)
• Original Assignee: E. I. du Pont de Nemours and Company (Corteva, Inc.)
• Inventors: Black, Cheryl, Wagenknecht, Dietmar, Rosenberg, Leonard S., Speicher, Earl R.
• Primary Examiner(s): WADDELL, FREDERICK
• Application Number:
  US07/203,836
• Time in Patent Office: 433 Days
• Field of Search: 514/538, 514/567
• US Class Current: 514/538
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/215 of carboxylic acids
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 9/12 Antihypertensives

Abstract

An injectable, aqueous pharmaceutical composition for the treatment of cardiac conditions comprising an effective amount of methyl 3-[4-(2-hydroxy-3-isopropylamino)propoxy]phenylpropionate hydrochloride (esmolol) for treating such a cardiac condition, said composition comprising about 1 mg to 250 mg of esmolol per milliliter of said injectable pharmaceutical composition; 0.01 to 0.02M buffer; said composition having a pH range of 4.5 to 5.5, the esmolol degrading in aqueous solution to produce 3-[4-(3-propionic acid)phenoxy]-1-isopropylamino-2-propanol hydrochloride, said 3-[4-(3-propionic acid)-phenoxyl]-1-isopropylamino-2-propanol hydrochloride having a pK in the pH range of said composition to thereby act as a secondary buffer to increase the buffer capacity and minimize the change in pH as degradation occurs, whereby the stability of esmolol in an aqueous composition is enhanced.

Claims

1. An injectable, aqueous pharmaceutical composition for the treatment of cardiac conditions comprising an effective amount of Methyl 3-[4-(2-hydroxy-3-isopropylamino)propoxy]phenylpropionate hydrochloride (esmolol) for treating such a cardiac condition, said composition comprising about 1 mg to about 250 mg of esmolol/mL of solution;

0.01 to 0.04 M buffer;

said composition having a pH range of about 4.5 to 5.5, the esmolol degrading in aqueous solution to produce 3-[4-(3-propionic acid)-phenoxy]-1-isopropylamino-2-propanol hydrochloride, said 3-[4-(3-propionic acid)-phenoxy]-1-isopropylamino-2-propanol hydrochloride having a pK in the pH range of said composition to thereby act as a secondary buffer to increase the buffer capacity without the addition of buffer and minimize the change in pH as degradation occurs, whereby the stability of esmolol in an aqueous composition is enhanced.

2. The composition of claim 1 wherein the buffer is selected from the group comprising acetate, tartrate, lactate, gluconate and phosphate buffer.

3. The composition of claim 2 wherein the buffer is acetate buffer.

4. The composition of claim 3 including about 10 mg/mL of solution.

5. The composition of claim 4 wherein the concentration of acetate buffer is about 0.05 M.

6. The composition of claim 5 wherein a pH of about 4.9 to about 5.1.

7. A stable, injectable, aqueous pharmaceutical composition for the treatment of cardiac conditions comprising an effective amount of Methyl 3-[4-(2-hydroxy-3-isopropylamino)propoxy]phenylpropionate hydrochloride (esmolol) for treating such a cardiac condition, said composition comprising about 10 mg of esmolol/mL of solution;

about 0.05 M buffer;

said composition having a pH range of about 4.5 to 5.5, the esmolol degrading in aqueous solution to produce 3-[4-(3-propionic acid)-phenoxy]-1-isopropylamino-2-propanol hydrochloride, said 3-[4-(3-propionic acid)-phenoxy]-1-isopropylamino-2-propanol hydrochloride having a pK in the pH range of said composition to thereby act as a secondary buffer to increase the buffer capacity without the addition of buffer and minimize the change in pH as degradation occurs, whereby the stability of esmolol in an aqueous composition is enhanced.

8. The composition of claim 7 having a pH of about 4.9 to about 5.1.