Sildenafil Citrate 2.5 mg/mL Oral Liquid

US Pharm. 2018;43(2):47-48.

Method of Preparation: Calculate the quantity of each ingredient for the amount to be prepared. Accurately weigh or measure each ingredient. Mix 50 mL of Ora-Plus with 50 mL of Ora-Sweet for use as the vehicle in this preparation. Obtain the required number of sildenafil citrate tablets or the required quantity of powder and place in a mortar. Pulverize the tablets, if used, to a fine powder. Add a small quantity of the Ora-Plus:Ora-Sweet mixture and mix to a smooth paste. Geometrically, add the remainder of the Ora-Plus:Ora-Sweet mixture to final volume and mix well. Package and label.

Use: Sildenafil citrate oral liquid has been used to treat pediatric pulmonary arterial hypertension in children in whom the risk-benefit profile of sildenafil is deemed acceptable.

Packaging: Package in tight, light-resistant containers.¹

Labeling: Keep out of reach of children. Shake well. Discard after ____ [time period].

Stability: A beyond-use date of up to 91 days may be used for this preparation.^1-4

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).⁵

Discussion: A number of stability studies have been conducted on oral liquid formulations of sildenafil for pediatric use. From these, it appears that sildenafil is relatively stable in vehicles, with an acidic pH around 4 to 5. Sildenafil for oral suspension at 10 mg/mL (Revatio) is commercially available with a beyond-use date of 60 days after reconstitution.

One study involved compounded sildenafil citrate in a citrate-buffered solution (0.1 M, pH 4) and either a syrup excipient (resulting in a suspension) or a sugar-free syrup excipient (resulting in a solution); both had pH values of approximately 4.2. Both the suspension and the solution were slightly pink and fruit-flavored. The suspension demonstrated stability for 91 days at both 4°C and 25°C; however, the solution was stable only for 30 days, possibly related to a nonredispersible sediment at the bottom of the container.³

A study by Nahata and colleagues that involved sildenafil citrate tablets (Revatio 20 mg) with a mixture of 1:1 Ora-Sweet and Ora-Plus at 2.5 mg/mL and pH 4.5-4.7 demonstrated stability of 91 days at both 4°C and 25°C. Also studied was a mixture of 1:7 (1% methyl cellulose:simple syrup) at pH 5.1 to 4.9 that also demonstrated stability of 91 days at both 4°C and 25°C.⁴

Sildenafil citrate (C₂₂H₃₀N₆O₄S.C₆H₈O₇, MW 666.70) occurs as a white to off-white, crystalline powder that is soluble 3.5 mg/mL in water. It is formulated as tablets equivalent to 25 mg, 50 mg, and 100 mg of sildenafil for oral administration. The tablets also contain microcrystalline cellulose, anhydrous dibasic calcium phosphate, croscarmellose sodium, magnesium stearate, hydroxypropyl methylcellulose, titanium dioxide, lactose, triacetin, and FD&C Blue #2 Aluminum Lake.^6,7

Ora-Plus is an oral suspending vehicle that accepts dilution of up to 50% or more with water, flavoring agents, or syrups while still retaining 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. Ora-Plus 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.⁸

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 it 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.⁹

REFERENCES

1. U.S. Pharmacopeia/National Formulary [current revision]. Rockville, MD: U.S. Pharmacopeial Convention, Inc; January 2018.
 2. Nahata MC, Morosco RS, Brady MT. Extemporaneous sildenafil citrate oral suspensions for the treatment of pulmonary hypertension in children. Am J Health Syst Pharm. 2006;63:254-257.
3. Provenza N, Calpena AC, Mallandrich M, et al. Design and physicochemical stability studies of paediatric oral formulations of sildenafil. Int J Pharm. 2014;460:234-239.
4. Nahata MC. Extended stability of morphine and sildenafil for oral use in infants and young children. IJPC. 2016;20:247-249.
5. Allen LV Jr. Standard operating procedure for performing physical quality assessment of oral and topical liquids. IJPC. 1999;3:146-147.
6. McEvoy GK, ed. AHFS Drug Information 2016. Bethesda, MD: American Society of Health-System Pharmacists; 2016:1918-1932.
7. Physicians’ Desk Reference. 70th ed. Montvale, NJ: PDR Network; 2016:1929-1936.
8. Ora-Plus product information. Allegan, MI: Perrigo; 2018.
9. Ora-Sweet product information. Allegan, MI: Perrigo; 2018.

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