A Simple and Economical Approach/Concept to Evaluate Quality of Pharmaceutical Products Based on an Improved Dissolution Testing Methodology

Often the quality of drug products is evaluated based on chemical tests, commonly described in different pharmacopeias such as the USP. These tests includes: assay (potency), uniformity of dosage form and dissolution test. Presently, these tests are conducted separately with three procedures. Furthermore, dissolution tests are also conducted using multiple product-specific procedures. This makes the current practice of evaluation of the quality of pharmaceutical products complex and resource (human and financial) intensive. Recently a new improved dissolution methodology, based on a modified spindle known as crescent-shaped spindle, has been proposed. Using the proposed methodology, all these tests may be conducted based on a single dissolution test procedure. Such an approach would, therefore, provide a simpler alternative to the current practice with significant economical benefits. The attributes of the proposed approach which lead to the concept of product evaluation based on a single dissolution test procedure, are described here by testing a number of diltiazem products having different strengths and release characteristics. The quality of drug products is evaluated based on chemical tests commonly described in different pharmacopeias such as USP. In general tests are conducted to establish presence of the expected amount of drug in the product (potency), uniformity or consistency of drug content in a product, such as, from tablet to tablet, and expected drug dissolution or release characteristics of a product. At present, these tests are conducted separately with at least three procedures. A new spindle known as crescent-shaped spindle has been proposed for improved drug dissolution testing [1-3]. The superiority of the new spindle appears to be due to its efficient extraction ability, because of improved productmedium interaction in the dissolution vessel. It may be argued that as all the above mentioned tests are based on the extraction of drug from a product, the new approach based on the new spindle may provide a common approach for these tests. This would provide a simpler alternative to the current practice, with a significant economical benefit. This article provides a discussion and experimental evidence showing that a simpler and more relevant testing approach based on dissolution testing may be used for an overall evaluation of the quality of pharmaceutical products. MATERIALS AND METHODS Pharmaceutical Products: IR (30and 60-mg) tablet and ER (120-mg once (CD) and twice (SR) a day) capsules of diltiazem products tested in the study were obtained from the local Canadian market. In total, 10 products were tested reflecting, 3 for each IR strengths, 3 for ER once-a-day and 1 for SR, from 3 manufacturers coded as manufacturers “A”, “B” and “C”. *Address correspondence to this author at the Banting Research Centre (A/L 2202C1), Tunney's Pasture, Ottawa, Ontario, K1A 0L2, Canada; Tel: 613957-3728; Fax: 613-941-8932; E-mail: [email protected] All other chemicals and solvents were of analytical grade and used as supplied by the suppliers. Stirring Spindle: The crescent-shaped [1] spindles were used for testing. The crescent-shaped spindle is designed to fit the commonly used apparatuses as a substitute for the Paddle or Basket spindle. The agitator has a stem part and the lower part is curved to conform to the shape of the vessel in which it is rotated, but with no direct contact with the surface of the vessel. The end of the stem conforming to the bottom part of the vessel has filamentary elements filling the gap between the stem and the bottom part of the vessel. Therefore, when the device attached to the vertical shaft rotates, the brush-type agitator will sweep along the bottom and sides of the vessel providing even distribution and mixing of the disintegrating material thus avoiding accumulation (coning). Instrumentation: The dissolution tests were conducted using a DISTEK 2100C system which is comprised of a bath with six vessels and met the physical and mechanical specifications as noted in the USP [4]. The dissolution tests were conducted using the crescent-shaped spindle at 25 rpm in all cases. Prior to use, the dissolution media were equilibrated at 37°C overnight to deaerate the medium so that bubble formation, due to escape of dissolved gasses during the test, was minimized. The tests for the diltiazem products were conducted using 900 mL water. The amount of diltiazem dissolved in each vessel was determined at various time intervals; up to three hours for the IR products and 24 hours for the ER and SR products. The dissolution sampling was achieved using an automated sampling system connected to an online UV diode-spectrophometer (Agilent 8453). The quantitation of 34 The Open Drug Delivery Journal, 2009, Volume 2 Saeed A. Qureshi diltiazem was done by ultraviolet absorbance at 240 nm of filtered portions of the solutions under test, in comparison with a reference solution having a known concentration of diltiazem standard [5]. Data Analysis: The data were collated and analysed using SAS software (SAS Institute, Cary, NC).