US Pharm. 2010;35(5):42-43.
Method of Preparation: Calculate the quantity of each ingredient for the amount to be prepared. Accurately weigh or measure each ingredient. Triturate the clopidogrel tablets to a fine powder in a mortar. Add a small quantity of Ora-Plus and mix well to form a smooth paste. Add the remainder of the Ora-Plus in portions and mix well. Add the Ora-Sweet to final volume and mix well. Package and label.
Use: Clopidogrel, an antiplatelet agent, is an aggregation inhibitor.
Packaging: Package in tight, light-resistant containers.
Labeling: Shake well before taking. Keep out of the reach of children. Discard after ____ [time period].
Stability: A beyond-use date of 60 days may be used for this preparation. In a stability study, at least 97% of intact drug was still present after 60 days, but the study lasted only 60 days.1,2
Quality Control: Quality-control assessment can include weight/volume, pH, specific gravity, active drug assay, color, rheologic properties/pourability, physical observation, and physical stability (discoloration, foreign materials, gas formation, mold growth).3
Discussion: Thrombotic risks are incurred by various pediatric disorders (e.g., Kawasaki disease, ischemic stroke, congenital defects), the placement of intracardiac stents and devices, and pediatric cardiac surgery. These risks have resulted in the need for more antiplatelet therapies in the pediatric population. Clopidogrel is a prodrug that is used to inhibit platelet aggregation and is beneficial in pediatric patients.2
Clopidogrel is available as clopidogrel bisulfate tablets containing 75 mg or 300 mg of clopidogrel as the bisulfate. These tablets are not amenable to administration to children owing to difficulty swallowing, and the tablets may not contain the required dosage for the individual patient. Splitting is not sufficiently accurate, so an alternative approach is required.2 To address the issues of ease of administration and dosing flexibility, an oral liquid dosage form is presented here.
In a stability study supporting this formulation, after 60 days, 97.3% of the clopidogrel remained at room temperature, and 99.5% remained after storage in the refrigerator. There was no appreciable change in the pH (about 2.65) of the preparation at either temperature. In addition, there was no detectable change in color, odor, or taste and no visible microbial growth in any of the samples.2
Clopidogrel bisulfate (C16H16ClNO2S•H2SO4, MW 419.9, Plavix) is a thienopyridine class inhibitor of P2Y12 ADP platelet receptors. It occurs as a white to off-white powder that is practically insoluble in water at neutral pH, but freely soluble at pH 1.
Plavix is available commercially as either pink, round, biconvex, debossed, film-coated tablets containing 97.875 mg of clopidogrel bisulfate—which is the molar equivalent of 75 mg of clopidogrel base—or as pink, oblong, debossed, film-coated tablets containing 391.5 mg of clopidogrel bisulfate, which is the molar equivalent of 300 mg of clopidogrel base.
In addition to clopidogrel bisulfate, each tablet contains hydrogenated castor oil, hydroxypropyl cellulose, mannitol, microcrystalline cellulose, and polyethylene glycol 6000 as inactive ingredients. The pink film coating contains ferric oxide, hypromellose 2910, lactose monohydrate, titanium dioxide, and triacetin and is polished with Carnauba wax.4
Ora-Plus is an oral suspending vehicle that accepts dilution of up to 50% or more with water, flavoring agents, or syrups and still retains its suspending properties. It has a pH of approximately 4.2 and an osmolality of about 230 mOsm/kg. It is a thixotropic vehicle with a viscosity of approximately 1,000 cps at 25°C. It contains purified water, microcrystalline cellulose, sodium carboxymethyl cellulose, xanthan gum, carrageenan, sodium phosphate, and citric acid as buffering agents, simethicone as an antifoaming agent, and potassium sorbate and methylparaben as preservatives.5
Ora-Sweet syrup vehicle is a flavoring vehicle for oral extemporaneous preparations. It is flavored with a citrus-berry flavor blend and contains glycerin and sorbitol to prevent “cap-lock,” a problem associated with many syrups. It is buffered to a pH of approximately 4.2 and has an osmolality of about 3,240 mOsm/kg. It contains purified water, sucrose, glycerin, sorbitol (5%), flavoring, sodium phosphate, and citric acid as buffering agents, and potassium sorbate and methylparaben as preservatives.6
REFERENCES
1. USP Pharmacists’ Pharmacopeia. 2nd ed. Rockville, MD: US Pharmacopeial Convention, Inc; 2008;775-779.
2. Skillman KL, Caruthers RL, Johnson CE. Stability of an extemporaneously prepared clopidogrel oral suspension. Am J Health Syst Pharm. 2010;67:559-561.
3. Allen LV Jr. Standard operating procedure for performing physical quality assessment of oral and topical liquids. IJPC. 1999;3:146-147.
4. Physicians’ Desk Reference 2010. 64th ed. Montvale, NJ: PDR Network; 2009:3027-3032.
5. Ora-Plus product information. Minneapolis, MN: Paddock Laboratories, Inc; 1992.
6. Ora-Sweet product information. Minneapolis, MN: Paddock Laboratories, Inc; 2004.
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