US Pharm. 2016;41(1):50-51.
Method of Preparation: Calculate the quantity of each ingredient for the amount to be prepared. Accurately weigh or measure each ingredient. Capsules—Calculate the required quantity of lactose for each capsule. Thoroughly mix the ingredients geometrically and encapsulate into the required number of capsules. Package and label. Suppositories—Calculate the required quantity of fatty-acid base. Thoroughly mix the powders to a uniform blend. Gently melt the fatty-acid base at up to 40°C. Slowly and with constant stirring, sprinkle in the blended powders and mix well. Pour into the suppository molds. Cool, trim (if necessary), package, and label.
Use: This formulation has been used in the management of migraine and episodic tension-type headaches.1
Packaging: Package in tight containers.
Labeling: Keep out of reach of children. Discard after ____ [time period].
Stability: A beyond-use date of up to 6 months may be used for these preparations.2
Quality Control: Capsules—Quality-control assessment can include weight–overall average weight, weight–individual weight variation, dissolution of capsule shell, disintegration of capsule content, active drug assay results, physical appearance (color, uniformity, extent of fill, locked status), and physical stability (discoloration, changes).3 Suppositories—Quality-control assessment can include weight, specific gravity, active drug assay, color, clarity, texture of surface, appearance, feel, melting test, dissolution test, physical observation, and physical stability.4
Discussion: These preparations are available commercially, in other countries, as Difmetrè in various dosage forms and strengths. This product has been reviewed for the acute treatment of migraine and for the treatment of episodic tension-type headache.5
Indomethacin (Indocin, C19H16ClNO4, MW 357.79) is a prototypical nonsteroidal anti-inflammatory drug that also exhibits analgesic and antipyretic activity. It is primarily used orally or rectally, but it is also effective when applied topically in a penetrating vehicle. Indomethacin occurs as a pale yellow to yellow-tan, crystalline, polymorphic powder with no more than a slight odor. Indomethacin is sensitive to light and melts at about 162°C. It is practically insoluble in water and sparingly soluble in alcohol.2,6
Caffeine (C8H10N4O2, MW 194.19) occurs as a white powder or as white, glistening needles, usually matted together. It is odorless and has a bitter taste. Caffeine is sparingly soluble in water and in alcohol. The hydrate is efflorescent in air.2
Prochlorperazine maleate (Compazine, Procomp, C20H24ClN3S.2C4H4O4, MW 606.09) occurs as a white or pale yellow, practically odorless, crystalline powder. It is practically insoluble in water and alcohol and should be stored in tight, light-resistant containers.2
Lactose (milk sugar, saccharum lactis, C12H22O11) is available either anhydrous or as the monohydrate. It is soluble in water to the extent of about 1 g in 4.63 mL, but it is practically insoluble in ethanol.7
Fatty-acid base (hard fat USP) is a mixture of glycerides of saturated fatty acids. These suppository bases consist mainly of mixtures of the triglyceride esters of the higher saturated fatty acids (C8-C18) with varying proportions of mono- and diglycerides. Numerous products are available that may be selected based upon their physical properties, including acid value, hydroxyl value, iodine value, melting point, saponification value, solidification point, and unsaponifiable matter. Hard fat occurs as a white mass that is almost odorless and free from rancid odor. It is greasy to the touch. On warming, hard fat melts to a colorless or slightly yellowish liquid. Hard fat is practically insoluble in water and slightly soluble in alcohol, and it is freely soluble in ether.2,8
1. Hoy SM, Scott LJ. Indomethacin/prochlorperazine/caffeine: a review of its use in the acute treatment of migraine and in the treatment of episodic tension-type headache. CNS Drugs. 2011;25:343-358.
2. U.S. Pharmacopeia 39/National Formulary 34. Rockville, MD: U.S. Pharmacopeial Convention, Inc; 2016.
3. Allen LV Jr. Standard operating procedure for performing physical quality assessment of powder-filled, hard-gelatin capsules. IJPC. 1999;3:232-233.
4. Allen LV Jr. Standard operating procedure for performing physical quality assessment of suppositories, troches, lollipops and sticks. IJPC. 1999;3:56-57.
5. Difmetrè. www.torrinomedica.it/farmaci/schedetecniche/Difmetre.asp. Accessed December 9, 2015.
6. McEvoy GK, ed. AHFS Drug Information 2012. Bethesda, MD: American Society of Health-System Pharmacists; 2012:2128-2139.
7. Edge S, Kibbe AH, Shur J. Lactose (anhydrous and monohydrate): In: Rowe RC, Sheskey PJ, Cook WG, Fenton ME, eds. Handbook of Pharmaceutical Excipients. 7th ed. London, England: Pharmaceutical Press; 2012:410-412,415-420.
8. Moreton RC. Suppository bases, hard fat. In: Rowe RC, Sheskey PJ, Quinn ME, eds. Handbook of Pharmaceutical Excipients. 6th ed. London, England: Pharmaceutical Press; 2009:722-726.
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