Tretinoin

METHOD OF 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. Mix the tretinoin, lidocaine hydrochloride and the potassium sorbate with the propylene glycol into a smooth paste.

4. Incorporate the Carbopol 934P and mix well.

5. Add approximately 85 mL of purified water and mix well.

6. Slowly add the triethanolamine until a pH in the range of approximately 5 to 6 is obtained, mixing with a paddle using slow rotations to minimize the incorporation of air into the preparation.

7. Add sufficient purified water to volume and mix well.

8. Package and label.

PACKAGING

Package in tight, light-resistant containers.1

LABELING

Keep out of reach of children. Use only as directed. For external use only.

STABILITY

A beyond-use date of up to 30 days is appropriate for this preparation.1

USE

Tretinoin has been used topically to enhance wound healing.2,6

QUALITY CONTROL

Quality-control assessment can include theoretical weight compared to actual weight, pH, specific gravity, active drug assay, color, clarity, texture, appearance, feel, rheological properties and physical observations.7

DISCUSSION

Tretinoin and lidocaine hydrochloride in combination provide pain relief and enhanced wound epithelialization. Tretinoin is a skin irritant and, when applied topically, may cause transitory stinging, a warm feeling with erythema and peeling. It will stimulate mitosis and turnover of follicular epithelial cells.

Tretinoin (C^sub 20^H^sub 28^O^sub 2^, MW 300.4, retinoic acid, vitamin A acid, all-trans retinoic acid) occurs as a yellow-to-light orange, crystalline powder that is insoluble in water and slightly soluble in alcohol. It should be preserved in tight containers, preferably under an atmosphere of an inert gas, protected from light.1,8

Lidocaine hydrochloride (C^sub 14^H^sub 22^N^sub 2^OHCl.H^sub 2^O, MW 288.81) occurs as a white, odorless, crystalline powder with a slightly bitter taste. It is very soluble in water (1:0.7) and in alcohol (1:1.5).1,8

Propylene glycol (C^sub 3^H^sub 8^O^sub 2^, MW 76.09) occurs as a clear, colorless, viscous, practically odorless liquid. It is miscible with 95% ethanol, glycerin and water.9

Carbopol 934P (a carbomer) can occur as white-colored, fluffy, acidic, hygroscopic powders with a slight characteristic odor. When carbomers are dispersed in water, an acidic colloidal solution of low viscosity will form that will thicken when an alkaline material, such as triethanolamine, is added.10

Triethanolamine (C^sub 6^H^sub 15^NO^sub 3^, MW 149.19, TEA, trolamine) is an alkalizing and emulsifying agent. It occurs as a clear, colorless-to-pale yellow viscous liquid. It is miscible with water and 95% ethanol.11

Potassium sorbate (C^sub 6^H^sub 7^O^sub 2^K, MW 150.22) occurs as a white, crystalline powder with a faint characteristic odor used as an antimicrobial preservative. It is soluble in water (l g in 1.72 mL), 95% alcohol (l g in 35 mL) and propylene glycol (1 gin 1.8mL).12

REFERENCES

1. US Pharmacopeia! Convention, Inc. United States Pharmacopeia 27National Formulary22. Rockville, MD: US Pharmacopeial Convention, Inc.; 2004: 1087-1088, 1873, 2345-2349.

2. Anthony J, Miller L, Dinehart SM. Topical tretinoin decreases healing times of electroepilation-induced wounds. Dermatologies 1991; 183(2): 129-131.

3. Raquette D, Badiavas E, Falanga V. Short-contact topical tretinoin therapy to stimulate granulation tissue in chronic wounds. J Am Ac ad Dermatol 2001; 45(3): 382-386.

4. Watcher MA, Wheeland RG. The role of topical agents in the healing of full-thickness wounds. J Dermatol Surg Oncol 1989; 15(11): 1188-1195.

5. Hung VC, Lee JY, Zitelli JA et al. Topical tretinoin and epithelial wound healing. Arch Dermatol 1989; 125(1): 65-69.

6. Kitano Y, Yoshimura K, Uchida KG et al. Pretreatment with topical alltrans-retinoic acid is beneficial for wo und healing in genetically diabetic mice. Arch Dermatol Res 2001; 293(10): 515-521.

7. Allen LV Jr. Standard operating procedure for performing physical quality assessment of ointments/creams/gels. IJPC 1998; 2(4): 308-309.

8. Sweetman SC. MARTINDALE: The Complete Drug Reference. 33rd ed. London: Pharmaceutical Press; 2002: 1126-1127, 1313-1317.

9. Weller PJ. Propylene glycol. In: Rowe RC, Sheskey PJ, Weller PJ, eds. Handbook of Pharmaceutical Excipients. 4th ed. Washington, DC: American Pharmaceutical Association; 2003: 521-523.

10. Koleng JJ, McGinity JW. Carbomer. In: Rowe RC, Sheskey PJ, Weller PJ, eds. Handbook of Pharmaceutical Excipients. 4th ed. Washington, DC: American Pharmaceutical Association; 2003: 89-92.

11. Goskonda SR, Lee JC. Triethanolamine. In: Rowe RC, Sheskey PJ, Weller PJ, eds. Handbook of Pharmaceutical Excipients. 4th ed. Washington, DC: American Pharmaceutical Association; 2003: 663-664.

12. Owen SC. Potassium sorbate. In: Rowe RC, Sheskey PJ, Weller PJ. Handbook of Pharmaceutical Excipients. 4th ed. Washington, DC: American Pharmaceutical Association; 2003: 506-507.

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