Diltiazem hydrochloride formulations

Diltiazem hydrochloride belongs to the benzothiazepine class of compounds. It was first synthesized in the laboratories of Tanabe Seiyaku Co., LTD in Japan and was granted its first patent in 1969 (3). The first non-patent literature reference to diltiazem appeared in 1970 (4). Since the introduction of diltiazem hydrochloride in pharmaceutical formulations, it has gained wide acceptance as an anti-anginal and antihypertensive agent. A search of Chemical Abstracts (1967-July, 1992) and Pharma-ceutical Abstracts (1974-July, 1992) produced over 200 bibliographic citations dealing with diltiazem or diltiazem hydrochloride. 

A stability-indicating high performance liquid chromatographic method is available for the formulated product of diltiazem hydrochloride. Diltiazem hydrochloride is separated from its major potential degradate, desacetyl diltiazem using an isocratic HPLC method. The method utilizes a Phenomenex IB... 

A gas chromatographic assay allows the determination of diltiazem hydrochloride in tablet formulations. The separation uses a 3% OV-210 on a Chromosorb W 80/100 mesh column with an oven temperature of 260°C (isothermally). A carrier gas flow rate of 50 mL/minute is used. The method allows the quantitation of diltiazem in the concentration range of 0.05 mg/mL to 0.2 mg/mL (67). 

Dhawan, S., B. Medhi, and S. Chopra, Formulation and evaluation of diltiazem hydrochloride gels for the treatment of anal Assures. Scientia Pharmaceutica, 2009. 77(2) 465. 

An example for the early incorporation of new scientific knowledge in dermatological practice by using an extemporaneous preparation is the treatment of chronic anal fissures with diltiazem hydrochloride. The mechanism of action is based on the reduction of the pressure in the anal sphincter. In comparison to organic nitrates diltiazem hydrochloride causes less adverse effects (headache). Based on published experiences with this treatment and the need for a stable preparation, formulations for a gel and a cream were developed (Table 12.1). 

Biodegradable copolymers of fumaric anhydride and isophthalic anhydride were synthesised by the melt condensation polymerisation of purified prepolymer mixtures and formulated into microspheres loaded with theophylline and diltiazem hydrochloride using a solvent extraction procedure. The important parameters of the microencapsulation process were identified and in vitro... 

The effects of massing time on the properties of the granules of hydrophilic polymer-based controlled-release formulations were studied by Timmins et al. (43). The formulations consisted of 30% sodium alginate, 10% HPMC, and 50% diltiazem hydrochloride or verapamil hydrochloride. The increase in massing time resulted in an increase in the mean granule size of the formulations. This could be true for all the matrix controlled release formulations, which contain a high concentration of the hydrophilic polymers. 

Prabu SL, Shirwaikar AA, Shirwaikar A, Ravikumar G, Kumar A, Jacob A. Formulation and evaluation of oral sustained release of diltiazem hydrochloride using rosin is matrix forming material. ARS Pharm. 50 (1) 32-42,2009. 

Turner SW, Jungbluth GL, Knuth DW. Effect of concomitant colestipol hydrochloride administration on the bioavailability of diltiazem from immediate- and sustained-release formulations. Biopharm Drug Dispos (2002) 23, 369-77. 

---