A stability-indicating HPLC procedure for determination of diltiazem hydrochloride in extemporaneously compounded oral liquids

A stability-indicating procedure for the determination of diltiazem hydrochloride in diltiazem hydrochloride (HCl) oral suspension and diltiazem HCl oral suspension, sugar free, is reported. Both suspensions were prepared from commercially available diltiazem HCl powder in a 1:1 (v/v) mixture of vehicle for oral solution and vehicle for oral suspension, and 1:1 (v/v) mixture of vehicle for oral solution, sugar free, and vehicle for oral suspension.
Mar 01, 2008

The stability of drugs in solid forms such as powders, tablets and capsules is usually determined very thoroughly by the drug's manufacturer. Based on stability study data, the shelf-life of a drug substance or a drug product is assigned. In addition to dispensing solid dosage forms to patients, pharmacists are frequently asked to compound oral liquid preparations for which the shelf-life or beyond-use date are assigned based on the pharmacist's best judgment — often without the benefit of stability data.

Liquid oral forms are in great demand for treating paediatric and geriatric patients who have difficulty swallowing solid oral dosage forms and for people with unique health needs that off-the-shelf prescription medicines cannot meet. Because compounded medications are a vital part of quality medical care, the drug stability information in liquid formulae must be available to compounding pharmacists so that they can assign a beyond-use date to compounded medicines.

Based on an informal survey mailed in 1994 to community and hospital pharmacies, the US Pharmacopeia (USP) Compounding Pharmacy Expert Committee developed a list of frequently compounded drugs and their concentrations in extemporaneously compounded oral liquids.1 Diltiazem HCl was among the drugs identified by the survey.

This article describes the development and validation of a stability-indicating HPLC procedure for the determination of diltiazem HCl in diltiazem HCl oral suspension and diltiazem HCl oral suspension, sugar free. The development of a stability-indicating HPLC procedure for the determination of diltiazem HCl in extemporaneously compounded oral liquids was based on the United States Pharmacopeia–National Formulary (USP–NF) monographs2,3 and on published findings of Allen and Erickson III.1 Both diltiazem HCl oral suspension and diltiazem HCl oral suspension, sugar free, were prepared from commercially available diltiazem HCl powder in a 1:1 (v/v) mixture of vehicle for oral solution and vehicle for oral suspension,4,5 and in a 1:1 (v/v) mixture of vehicle for oral solution, sugar free,6 and vehicle for oral suspension, respectively.

Experimental

Chemicals. USP diltiazem HCl reference standard (RS); USP desacetyl diltiazem HCl reference standard (RS) (Rockville, MD, USA); diltiazem HCl; microcrystalline cellulose; xanthan gum; carrageenan; carboxymethylcellulose sodium; citric acid; diabasic sodium phosphate; simethicone; potassium sorbate; methylparaben; sucrose; glycerin; sorbitol and sorbitol solution; saccharin sodium; and sodium citrate were from Spectrum Chemicals (New Brunswick, NJ, USA); d-10-camphorsulfonic acid was from ACROS (Geel, Belgium); sodium acetate and 0.1 N sodium hydroxide solution were from J.T. Baker (Phillipsburg, NJ, USA); hydrochloric acid and acetonitrile were from Fisher (Pittsburg, PA, USA); hydrogen peroxide was from Sigma (Saint Louis, MO, USA); methanol was from B&J Brand (Morristown, NJ, USA); and deionized water was obtained on Milli-Q reagent water system by Millipore. All vehicle ingredients were USP–NF grade. All chemicals were reagent grade or better.

HPLC system. The Agilent 1100 Series included a quaternary pump, autosampler, diode array UV detector, vacuum degasser, Chemstation chromatographic software and Waters μ-Bondapak C18 (30 cm=3.9 mm, 5 μm) or Phenomenex Bondeclone 10 C18 (30 cm=3.9 mm, 10 μm). Injection volume was 10 μL. Flow rate 1.6 mL/min.

Mobile phase. The mobile phase was prepared by mixing acetonitrile, methanol and buffer (1:1:2, v/v/v). To prepare the buffer, 2.3 g of d-10-camphorsulfonic acid was dissolved in 2000 mL of 0.1 M sodium acetate and adjusted the pH to 6.2 by adding 0.1 N sodium hydroxide. 0.1 M sodium acetate was prepared by dissolving 27.2 g of sodium acetate in 2.0 L of water.

Vehicles and placebos. Vehicle for oral solution, vehicle for oral suspension and vehicle for oral solution, sugar free, were prepared as described in USP 29–NF 24. A 1:1 (v/v) mixture of vehicle for oral solution and vehicle for oral suspension can be also called Placebo 1. A 1:1 (v/v) mixture of vehicle for oral solution, sugar free, and vehicle for oral suspension can be also called Placebo 2.