Diltiazem Hydrochloride Compounded Cream

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION 

Diltiazem Hydrochloride Compounded Cream contains NLT 90.0% and NMT 110.0% of the labeled amount of diltiazem hydrochloride (C₂₂H₂₆N₂O₄S . HCl). Prepare Diltiazem Hydrochloride Compounded Cream 20 mg/g¹ as follows (see Pharmaceutical Compounding—Nonsterile Preparations 〈795〉).

a PCCA, Houston, TX. 

FICIAL 

In an appropriately sized electronic mortar and pestle container, add 50 g of VersaBase Cream, place the Diltiazem Hydrochloride and Glycerin on top, and add sucient VersaBase Cream to bring to nal weight. Mix the mixture with an electronic mortar and pestle for 2 min at a speed of about 1500 rpm. Process through an ointment mill once at the middle setting and once at the nest setting to reduce the particle size of the active ingredient and to reduce air content of the preparation. Return the mixture to the electronic mortar and pestle container and mix again for 1 min at a speed of about 1100 rpm. 

2 ASSAY 

2.1 Procedure 

Solution A: 5.44 g/L of potassium phosphate dibasic in water, adjusted with phosphoric acid to a pH of 7.5. Pass through a polyvinyl diuoride lter of 0.22-µm pore size. 

Diluent: Methanol and water (80:20) 

Mobile phase: See Table 1. 

Table 1 

Standard solution: 0.1 mg/mL of USP Diltiazem Hydrochloride RS, prepared as follows. Transfer about 20 mg of USP Diltiazem Hydrochloride RS to a 200-mL volumetric ask and add about 150 mL of Diluent. Sonicate for 2 min until completely dissolved. Dilute with Diluent to volume and shake or vortex until well mixed. 

Sample solution: Transfer approximately 2 mL of Cream to a 3-mL syringe, taking care to minimize air bubbles. Transfer this Cream to a 1-mL syringe with the piston removed until the syringe is fully lled. Insert the piston and move the piston to about 5 mm above the 1-mL mark. Wipe the outside of the 1-mL syringe, using a delicate task wipe to remove any excess cream. Weigh the 1-mL syringe, recording the weight to 0.01 mg (initial). Precharge a 200-mL volumetric ask with approximately 10 mL of 2-propanol, ensuring the neck of the ask is wetted. Transfer the Cream from the 1-mL syringe to the volumetric ask. Keep the syringe at the center of the ask to try to minimize the Cream sticking to the neck. Weigh the empty syringe again, recording the weight to 0.01 mg (nal). The difference between the initial and final weight should be between 900 and 1100 mg. Vortex the volumetric ask for at least 3 min to break the Cream. Sonicate for 5 min. Vortex for an additional 2 min. Add sucient Diluent to bring the ask to volume and vortex or shake for 2 min. The resultant solution should be partially cloudy. Pass through a polyvinyl diuoride lter of 0.22-µm pore size, discarding the rst 3 mL, and then transfer to HPLC vials.

Chromatographic system (See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm 

Columns 

Guard: 4.0-mm × 3-mm; 5-μm packing L1 

Analytical: 4.6-mm × 15-cm; 5-μm packing L1 

Temperatures 

Autosampler: 15° 

Column: 30° 

Flow rate: 1 mL/min 

Injection volume: 20 µL 

System suitability 

Sample: Standard solution 

[Note—The retention time for diltiazem hydrochloride is about 11.4 min.] 

Suitability requirements 

Tailing factor: NMT 2.0 

Relative standard deviation: NMT 2% for replicate injections 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of diltiazem hydrochloride (C₂₂H₂₆N₂O₄S . HCl) in the portion of Cream taken: 

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of diltiazem hydrochloride from the Sample solution 

r_s = peak response of diltiazem hydrochloride from the Standard solution 

C_s = concentration of USP Diltiazem Hydrochloride RS in the Standard solution (mg/g) 

C_u = nominal concentration of diltiazem hydrochloride in the Sample solution (mg/g) 

Acceptance criteria: 90.0%–110.0% 

3 SPECIFIC TESTS 

pH 〈791〉: 4.1–5.1 

Appearance: White opaque cream 

4 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Package in a tight, light-resistant plastic tube. Store at controlled room temperature. 

Beyond-Use Date: NMT 90 days after the date on which it was compounded when stored at controlled room temperature. • Labeling: Label it to indicate that it is for external use only and to state the Beyond-Use Date. 

USP Reference Standards 〈11〉 

USP Diltiazem Hydrochloride RS▲ (USP 1-Aug-2022) 

1 This formulation meets the requirements in Antimicrobial Effectiveness Testing 〈51〉.