Diltiazem

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 diltiazem with the propylene glycol to form a smooth paste.

4. Incorporate the lecithin:isopropyl palmitate solution and mix well.

5. Add sufficient Pluronic 20% solution and mix using a shear action method until uniform.

6. 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.

Note: When counseling a patient concerning this preparation it is advisable to explain its temperature-dependent viscosity. As the preparation is rubbed into the skin and warms up, it may becom,e slightly m,ore viscous and resistant to rubbing.

STABILITY

A beyond-use date of 30 days would be appropriate for this preparation.1

USE

Diltiazem in Pluronic lecithin organogel has been used in the treatment of wounds by application to the intact skin surrounding the wound.

QUALITY CONTROL

Quality-control assessment can include theoretical weight compared to actual weight, specific gravity, active drug assay, color, texture-surface, texture-spatula spread, appearance, feel, rheological properties and physical observations.2

DISCUSSION

Diltiazem hydrochloride has been used in the treatment of anal fissures.3-6 Its application to topical wounds is more recent, and it is generally applied to the skin immediately adjacent to the wound area.

Diltiazem hydrochloride (C^sub 22^H^sub 26^N^sub 2^O^sub 4^S-HCl, MW 450.98) is a benzothiazepine-derivative calcium-channel blocker. It occurs as a white, odorless, crystalline powder or as small crystals. It is freely soluble in water and is sparingly soluble in dehydrated alcohol. It melts with some decomposition at about 210°C.1

Propylene glycol (C3H8O2, MW 76.09) occurs as a clear, colorless, viscous, practically odorless liquid with a sweet taste somewhat resembling glycerin. It has a specific gravity of 1.038 g/mL and is miscible with 95% ethanol, glycerin and water.7

Lecithin (egg lecithin, soybean lecithin, vegetable lecithin) describes a complex mixture of acetone-insoluble phosphatides. Lecithin derived from vegetable sources has a bland or nut-like taste and varies from brown to light yellow, depending upon whether bleached or unbleached. Lecithin is practically insoluble in water, polar solvents and cold vegetable and animal oils; however, when mixed with water it hydrates to form emulsions. Lecithin should be stored in well-closed containers and be protected from light.8

Isopropyl palmitate (C^sub 19^H^sub 38^SO^sub 2^, MW 298.51) is a colorless, mobile liquid with a very slight odor that is used as an emollient, oleaginous vehicle and a solvent; it has good spreading characteristics. It is soluble in acetone, castor oil, cottonseed oil, alcohol and mineral oil.9

Pluronic 20% solution is a poloxamer. Poloxamers occur as white-colored, waxy, free-flowing granules or as cast solids that are practically odorless and tasteless. Poloxamer 407 (Pluronic F-127) is generally available in powdered form. It is freely soluble in water, alcohol and isopropyl alcohol.10

REFERENCES

1. US Pharmacopeial Convention, Inc. United States Pharmacopeia 27NationalFormulary 22. Rockville, MD: US Pharmacopeial Convention, Inc.; 2004: 624-625, 2345-2349.

2. Alien LV Jr. Standard operating procedure for performing physical quality assessment of ointments/creams/gels. IJPC1998; 2; 308-309.

3. Jonas M, Neal KR, Abercrombie JF et al. A randomized trial of oral vs. topical diltiazem for chronic anal fissures. Dis Colon Rectum 2001; 44(8): 1074-1078.

4. Carapeti EA, Kamm MA, Phillips RK. Topical diltiazem and bethanechol decrease anal sphincter pressure and heal anal fissures without side effects. Dis Colon Rectum 2000; 43(10): 1359-1362.

5. Carapeti EA, Kamm MA, Evans BK et al. Topical diltiazem and bethanechol decrease anal sphincter pressure without side effects. Gut 1999; 45(51:719-722.

6. Jonas M, Speake W, Scholefield JH. Diltiazem heals glyceryl trinitrateresistant chronic anal fissures: A prospective study. Dis Colon Rectum 2002; 45(8): 1091-1095.

7. 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.

8. Fowler K. Lecithin. In: Rowe RC, Sheskey PJ, Weller PJ, eds. Handbook of Pharmaceutical Excipients. 4th ed. Washington, DC: American Pharmaceutical Association; 2003: 340-342.

9. Taylor AK. lsopropyl palmitate. In: Rowe RC, Sheskey PJ, Weller PJ, eds. Handbook of Pharmaceutical Excipients. 4th ed. Washington, DC: American Pharmaceutical Association; 2003: 314-315.

10. Collett JH. Poloxamer. In: Rowe RC, Sheskey PJ, Weller PJ, eds. Handbook of Pharmaceutical Excipients. 4th ed. Washington, DC: American Pharmaceutical Association; 2003: 447-450.

Copyright International Journal of Pharmaceutical Compounding Jul/Aug 2004
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