Acesulfame

Just a glance at a pharmacy shelf reveals the small number of commercially available medications in oral liquid form. Mainly for stability reasons, but also because of economic motives, pharmaceutical companies tend to manufacture drugs in solid oral forms rather than liquid oral forms. Furthermore, 80% of prescription drugs approved by the US Food and Drug Administration (FDA) for human use are not approved for use in children.1 Extemporaneous pharmacy compounding fills this gap and provides effective, personalized treatment for children in need of a medication that may not be commercially available.

This review focuses on practical, frequently used formulations for compounding oral liquid forms. The compounding pharmacist should perform quality control tests on the final preparation according to pharmacy standards for extemporaneous oral liquid preparations.2

Vehicles and Stock Solutions

Vehicles and basic stock solutions allow the pharmacist to shorten prescription compounding time and improve preparation quality. When the solution contains sweetening or flavoringagents, it becomes much easier to add them as needed during the compounding process once the final preparation is liquid.

Vanillin 2% w/v Solution3

Method of Preparation

1. Weigh and/or measure each ingredient accurately.

2. Dissolve the powder in the alcohol and complete the volume.

3. Package the preparation in an amber glass bottle.

Main Uses

This solution is used as a flavoring agent. It may be used alone or in association with other flavors in an oral liquid preparation.

Stability Information

Recommended packaging: Amber glass bottle, tightly closed

Storage recommendation: Under refrigeration and protected from light

Recommended beyond-use date: 60 days

Fructose 60% w/v Sweetening Concentrated Solution4

Method of Preparation

1. Weigh and/or measure precisely each ingredient.

2. Add the fructose, saccharin, cyclamate, and sodium benzoate to a beaker.

3. Add 51 mL of the purified water and mix well.

4. Heat the mixture to 60° to 65°C, mixing well until a homogenous clear solution is obtained.

5. Filter the mixture through gauze or an appropriate paper fdter.

6. Complete the volume with purified water and mix well.

7. Package the preparation in a dropper bottle.

Main Uses

This solution is used as a sweetening agent and as an adjuvant sweetener in preparations that already contain other sweetening agents. The compounder may use this solution for final "touch-ups" in masking bitterness of drugs by adding drops to the liquid preparation during the process.

Stability Information

Recommended packaging: Dropper bottle, for easily adding into solutions

Storage recommendation: Room temperature

Recommended beyond-use date: 180 days

Methylcellulose 1% to 5% Gel5

Method of Preparation

1. Weigh and/or measure each ingredient accurately.

2. Divide the water in two equal parts.

3. Cool half the water in the refrigerator.

4. Heat the other half of the water until it boils, then dissolve the sodium benzoate in the water.

5. Sprinkle the methylcellulose on the solution slowly, mixing constantly until completely dispersed.

6. Remove from heat and immediately add the cool water. Continue mixing until a clear, viscous gel is formed.

7. Package the preparation in an appropriate container.

Main Uses

This solution is used as a suspending agent. A final concentration of 0.5% of methylcellulose in the preparation is usually required to suspend the majority of drugs. As a general recommendation, 50% of a 1% methylcellulose gel should be added to the preparation and then the volume should be completed with a different vehicle such as sorbitol 70%, simple syrup, purified water, or flavored syrup.

Stability Information

Recommended packaging: Glass or plastic container

Storage recommendation: Room temperature

Recommended beyond-use date: 180 days

Cocoa Syrup6

Method of Preparation

1. Weigh and/or measure each ingredient accurately.

2. Dissolve the sodium chloride and sodium benzoate in 32.5 mL of water heated to 850C. Turn heat off.

3. Add the sugar, glycerin, and glucose. Turn the heat on again and mix the solution with a hand mixer.

4. Slowly add the cocoa.

5. Turn off the heat and let the temperature cool to 4O0C.

6. Dissolve the vanillin in a small quantity of alcohol.

7. Add the dissolved vanillin to the cooled mixture and mix well.

8. Let the solution cool until it reaches room temperature.

9. Complete to volume with purified water.

Main Uses

This syrup is used as a sweetened and flavored vehicle in oral liquid preparations. It may be used as the single vehicle in a preparation or in combination with other vehicles, such as suspension vehicles or other flavoring agents, such as vanilla, marshmallow, or mint.

Stability Information

Recommended packaging: Glass or plastic amber container

Storage recommendation: Room temperature

Recommended beyond-use date: 6 months

Sugar-Free Syrup3

Method of Preparation

1. Dissolve the steviosides, acesulfame, and sodium benzoate in 30 mL of water.

2. Gently heat 60 mL of the purified water and incorporate the xanthan gum. Mix until the gum is completely dispersed.

3. Add the xanthan gum to the remaining ingredients and mix well.

4. Complete to volume with water and mix until the preparation turns clear.

Main Uses

A sweetened, sugar-free vehicle, this syrup is appropriate for patients with diabetes and patients on hypocaloric diets.

Stability Information

Recommended packaging: Glass or plastic amber container

Storage recommendation: Room temperature

Recommended beyond-use date: 1 year

Captopril 1-mg/mL Oral Solution79

Method of Preparation

1. Weigh and/or measure each ingredient accurately.

2. Triturate the solid ingredients in a glass mortar and dissolve the powder in 30 mL of water.

3. Add the flavoring and part of the syrup to about 95 mL.

4. Check the pH and if needed adjust to 3 to 4 with a 20% citric acid solution.

5. Complete the volume with the simple syrup.

6. Dispense the preparation in an amber glass bottle.

Note: Filling the head space with nitrogen is recommended, if nitrogen is available.

Stability Information

Stability pH: 2 to 4

Recommended packaging: Amber glass bottle

Storage recommendation: Under refrigeration

Recommended auxiliary labels: KEEP REFRIGERATED

Recommended beyond-use date: 56 days

Commonly Prescribed Pediatric Oral Liquid Preparations

These formulas describe the therapeutic category of the drug, formulation ingredients, method of preparation, stability information, and related references for each specific preparation. It is important to mention that many of these formulas recommend flavoring agents, which vary greatly from brand to brand in some important physicochemical properties such as pH. Therefore, the compounder must check the pH of each flavoring agent and match its pH with the preparation's final pH range; the flavoring agent pH should significantly differ from the desired final pH in the preparation.

DMSA 100-mg/5-mL Oral Suspension2,10-14

Method of Preparation

1. Weigh and/or measure each ingredient accurately.

2. Triturate all solid ingredients together in a mortar.

3. Add the propylene glycol and flavoring and mix well.

4. Add the methylcellulose solution and mix well.

5. Complete to volume with purified water and mix well.

6. Dispense the preparation in an amber glass bottle.

Stability Information

Recommended packaging: Amber glass bottle

Storage recommendation: Under refrigeration

Recommended auxiliary labels: SHAKE WELL BEFORE TAKING and KEEP REFRIGERATED

Recommended beyond-use date: 14 days

Omeprazole 20-mg/5-mL Oral Buffered Suspension2,5-17

Method of Preparation

1. Weigh and/or measure each ingredient accurately.

2. In a mortar, empty the contents of the capsules and add 5 mL of dehydrated alcohol. Let the mixture rest for 5 minutes to soften the pellets.

3. Triturate the pellets until reduced to a powder and the alcohol evaporates.

4. Add the silica gel, steviosides, sodium bicarbonate, acesulfame, sodium metabisulfite, and EDTA disodium and triturate well.

5. Add the glycerin slowly until a smooth paste is formed.

6. Slowly add simple syrup until suspension of the powders is observed.

7. Add the flavoring agents and methylparaben and mix well.

8. Transfer the mixture to graduated glassware; rinse the mortar with the rest of the syrup.

9. Check the pH, and if needed, adjust to 9 to 9.5 with a sodium hydroxide 40% solution.

10. Complete to volume with purified water.

11. Transfer the solution to an amber glass bottle and let the solution rest for 5 to 6 hours uncovered so any carbon dioxide that might have been produced may be released.

Note: The bottle containing the preparation should be capped before dispensing.

Stability Information

Stability pH: 7.8 to 11 (maximum stability at pH 11)

Recommended packaging: Amber glass bottle

Storage recommendation: Under refrigeration

Recommended auxiliary labels: SHAKE WELL BEFORE TAKING and KEEP REFRIGERATED

Recommended beyond-use date: 14 days

Possible chemical degrading process: Oxidation in acidic pH

Amiodarone 5-mg/mL Oral Suspension18,19

Method of Preparation

1. Weigh and/or measure each ingredient accurately.

2. Triturate, in a glass mortar, the amiodarone with the propylene glycol until a smooth paste is formed.

3. Add the flavoring and the methylcellulose gel:syrup to about 90 mL and slowly mix well.

4. Check the pH and, if needed, adjust to 4.4 with citric acid 25% solution to lower the pH, or with a potassium citrate 25% solution to increase the pH. Mix well.

5. Complete to volume with the methylcellulose gel:syrup and mix well.

6. Dispense the preparation in a glass amber bottle.

Stability Information

Stability pH: 4.4

Recommended packaging: Amber glass bottle

Storage recommendation: Under refrigeration

Recommended auxiliary labels: SHAKE WELL BEFORE TAKING and KEEP REFRIGERATED

Recommended beyond-use date: 91 days

Possible chemical degrading process: Hydrolysis

Albendazole 100-mg/5-mL Sugar-Free Oral Suspension20,21

Method of Preparation

1. Weigh and/or measure each ingredient accurately.

2. Triturate all solid ingredients in a mortar.

3. Levigate the powders with the propylene glycol until a smooth paste is formed.

4. Add the Polysorbate 80.

5. Add the flavoring agents and mix well.

6. Slowly add the purified water. Mix well until ingredients are completely dispersed and a homogenous mixture forms.

7. Transfer the mixture to a graduated container.

8. Complete the volume with purified water and mix well.

9. Dispense the preparation in an amber glass bottle.

Stability Information

Recommended packaging: Amber glass bottle

Storage recommendation: Controlled room temperature

Recommended auxiliary labels: SHAKE WELL BEFORE TAKING

Recommended beyond-use date: 180 days

References

1. Chan DS. Stability issues for compounding extemporaneous prepared oral formulations for pediatric patients. IJPC2001; 5(1): 9-12.

2. US Pharmacopeial Convention, Inc. United States Pharmacopeia 27NationalFormulary22. Rockville, MD: US Pharmacopeial Convention, Inc.; 2003: 270-271, 2197-2201, 2458, 3531-3535.

3. Ferreira AO, Souza GF. Preparações Orals Liquidas. São Paulo, Brasil: Pharmabooks; 2005: 373, 393.

4. Ferreira AO. Guia Prático da Farmácia Magistral. 2a. edição. Sâo Paulo, Brasil: Pharmabooks; 2002: 337-341.

5. [No author listed.] Extemporaneous Oral Liquid Dosage Preparations. Toronto, Ontario: Canadian Society of Hospital Pharmacists; 1988:10.

6. Troy D, ed. Remington: The Science and Practice of Pharmacy. 20th ed. Philadelphia, PA: Lippmcott, Williams & Wilkins; 2000: 655-656.

7. Nahata MC, Morosco RS, Hippie TF. Stability of captopril in three liquid dosage forms. Am J Hosp Pharm 1994; 51(1): 95-96.

8. Pereira CM, Tam YK. Stability of captopril in tap water. Am J Hosp Pharm 1992; 49(3): 612-615.

9. Connors KA, Amidon GL, Stella VJ. Chemical Stability of Pharmaceutical. 2nd ed. New York, NY: John Wiley and Sons; 1986: 422-423.

10. Budavari S. The Merck Index. 12th ed. Whitehouse Station, NJ: Merck & Co. Inc.; 1996:1515.

11. Klaasen CD. Heavy metals and heavy metal antagonists. In: Hardman JG, Limbird LE, Gilman AG et al, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill; 2001:1851-1876.

12. Higton FR, Thurgood DM. Aspartame. In: Wade A, WellerPJ, eds. Physicians' Desk Reference. 52nd ed. Montvale, NJ: Medical Economics Co.; 1998: 2568-2569.

13.Wade A, Weller PT. Methylcellulose. In: Handbook of Pharmaceutical Excipients. 2nd ed. Washington. DC: American Pharmaceutical Association; 1994:407-408.

14. Allen LV Jr. Dimercaptosuccinic acid 100-mg/5-mL suspension. IJPC 1998; 2(6): 440.

15.Quercia RA, Fan C, LiuXetal. Stability of omeprazole in an extemporaneously prepared oral liquid. Am J Health Syst Pharm 1997; 54(16): 1833-1836.

16. Mathew M, Gupta VD, Bailey RE. Stability of omeprazole solutions at various pH values as determined by high-performance liquid chromatography. Drug Dev lnd Pharm 1995; 21: 965-971.

17. Phillips JO, Metzler MH, Palmieri MT et al. A prospective study of simplified omeprazole suspension for the prophylaxis of stress-related mucosal damage. Crit Care Med 1996; 24(11 ): 1793-1800.

18. Nahata MC. Stability of amiodarone in oral suspension stored under refrigeration and at room temperature. Ann Pharmacother 1997, 31(7-8): 851-852.

19.Nahata MC, Morosco RS, Hippie TF. Stability of amiodarone in extemporaneous oral suspensions prepared from commercially available vehicles. J Fed Pharm Pract 1999; 4(4): 186-189.

20. Sweetman SC, ed. MAHTINDALE: The Complete Drug Reference. 32nd ed. London: Pharmaceutical Press; 1999:1229-1230.

21. Niazi SK. Handbook of Pharmaceutical Manufacturing Formulations - Liquid Products. Boca Raton, FL: CRC Press; 2004: 70.

Simonne Fonseca, RPh

Content Editor

Compounding Today. com

Pearland, Texas

Address correspondence to Simonne Fonseca, RPb, Content Editor, CompoundingToday.com. E-mail: simonne@compotindingtoday.com

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