Amitriptyline

METHOD OF PREPARATION

Note: This preparation should be prepared in n laminar airflow hood in a ckanroom or via isolation barrier technology by a validated aseptic compounding pharmacist using strict aseptic technique. This is a high-risk preparation.

1. Calculate the required quantity of each ingredient for the total amount to be prepared.

2. Accurately weigh and/or measure each ingredient.

3. 1 leat about 90 m L of sterile water for injection to about 80°C].

4. Dissolve the methylparaben and propylparaben and cool the solution to room temperature.

5. Add the ainitriptylinc hydrochloridc and dextrose and mix until dissolved.

6. Adjust to a pH of 4 to 6.

7. Add sufficient sterile water for injection to volume and mix well.

8. Filter through a sterile 0.220 -µm filter into sterile vials.

9. Package and label.

PACKAGING

Package in tight, light-resistant containers.1

LABELING

Keep out of reach of children. Use only as directed. Store at controlled room temperature.

STABILITY

If not sterility tested: A beyond-usc date of up to 24 hours at room temperature, up to 3 days at refrigerated temperature (2 to 8µC), or up to 45 days if fro/,en can be used for this preparation.'

If sterility tested: A beyond-use date of up to 6 months can be used for this preparation because this formulation was formerly commercially available with supporting stability data.1

USE

Ainitriptylinc injection has been used in the treatment of anxiety disorders and other conditions, as described in the discussion.

QUALITY CONTROL

Quality-control assessment can include weight/volume, physical observation, pH, specific gravity, osmolality, assay, color, clarity, paniculate matter, sterility and pyrogenicity.2,3

DISCUSSION

Amitriptyline, a dibenzocycloheptcne-dcrivative tricyclic antidepressant, is a veiy diverse agent and has been used in the treatment of anxiety disorders, depression, headache, hiccup, hyperactivity, interstitial cystitis, irritable bowel syndrome, micturition disorders, narcoleptic syndrome, pain, pathological crying or laughing, premenstrual syndrome, schizophrenia, skin disorders, smoking cessation and stuttering.4

Amitriptyline hydrochloride (C^sub 20^H^sub 23^NJlCl, MW 313.86) occurs as a white or practically white, odorless or practically odorless, crystalline powder or small crystals. It is freely soluble in water and in alcohol. Amitriptyline hydrochloride injection contains not less than 90.0% and not more than 110.0% of the drug. The pH of the official injection is between 4.0 and 6.0.'

Dextrose (C^sub 6^H^sub 12^O^sub 6^.H^sub 2^O, MW 180.6, anhydrous; MW 198.17, monohydratc) occurs as odorless, sweet-tasting, colorless crystals or as a white crystalline or granular powder. It is soluble in water (l g in 1 mL), 95% ethanol (1 in 60) and glycerin.3

Methylparaben (C^sub 8^H^sub 8^O^sub 3^ methyl hydroxybenzoate, methyl parahydroxybenzoate) is available as colorless crystals or as a white, crystalline powder that is odorless, or almost odorless, and has a slight burning taste.6

Propylparaben (CH^sub 10^H^sub 12^O^sub 3^, prooyI hydroxyben/,oatc, propyl parahydiOxybenzoatc) is available as a white, crystalline, odorless and tasteless powder.7

Hydrochloric acid (HCl, MW 36.46) occurs as a clear, colorless, fuming aqueous solution of hydrogen chloride that has a pungent odor.8

Sodium hydroxide (NaOH, MW 40.00, caustic soda, soda lye) occurs as dry, very deliquescent, white or almost white sticks, pellets or fused masses that are hard and brittle.9'10

REFERENCES

1. United States Pharmacopeial Convention, Inc. United States Pharmacopeia 27-NationalFormulary22. Rockvitle, MD: US Pharmacopeial Convention, Inc.; 2004: 130-131,2345-2349,2749.

2. Alien LV Jr. Standard operating procedure for paniculate testing for sterile products. /JPC1998; 2(1): 78.

3. Alien LV Jr. Standard operating procedure: Quality assessment for injectable solutions. /JPC1999; 3(5]: 406-407.

4. Sweetman SC. MAHTINDALE: The Complete Drug Reference. 33rd ed. London: Pharmaceutical Press; 2002: 273-279.

5. Day A. Dextrose. In: Rowe RC, Sheskey PJ, Weller PJ, eds. Handbook of Pharmaceutical Excipients. 4th ed. Washington, DC: American Pharmaceutical Association; 2003: 200-202.

6. Reiger MM. Methylparaben. In: Rowe RC, Sheskey PJ, Weller PJ, eds. Handbook of Pharmaceutical Excipients. 4th ed. Washington, DC: American Pharmaceutical Association; 2003:390-394.

7. Rieger MM. Propylparaben. In: Rowe RC, Sheskey PJ, Weller PJ, eds. Handbook of Pharmaceutical Excipients. 4th ed. Washington, DC: American Pharmaceutical Association; 2003: 526-528.

8. Owen SC. Hydrochloric Acid. In: Rowe RC, Sheskey PJ, Weller PJ, eds. Handbook of Pharmaceutical Excipients. 4th ed. Washington, DC: American Pharmaceutical Association; 2003: 281-282.

9. Kibbe AH. Sodium hydroxide. In: Rowe RC, Sheskey PJ, Weller PJ, eds. Handbook of Pharmaceutical Excipients. 4th ed. Washington, DC: American Pharmaceutical Association; 2003: 566-567.

10. Reynolds JE, ed. MAHTINDALE: The Extra Pharmacopeia. 30th ed. London: The Pharmaceutical Press; 1993: 1415.

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