Paddle testers

Major components of dissolution equipment are the tester (including typically, but not limited to, spindle assemblies, belt, motor, tension adjuster, and circulator pump and hoses), water bath, paddles, baskets and shafts, vessels, samplers, and analyzers. Mechanical aspects, such as media temperature, paddle or basket speed, shaft centering and wobble, and vibration can all have a significant impact on the dissolution of the product. Mechanical and chemical calibration should therefore be conducted periodically, usually every 6 months, to ensure that the equipment is working properly. 

Various dissolution test systems have been developed and several of them now enjoy compendial status in pharmacopeias, for example the reciprocating cylinder (United States Pharmacopeia Apparatus 3), the flow-through apparatus [European Pharmacopoeia (Pharm. Eur.) 2.9.3], or the apparatus for transdermal delivery systems, such as the paddle over disc. Hydrodynamic properties of these and other apparatus have been described only sparingly. The paucity of quantitative data related to hydrodynamics of pharmacopeial dissolution testers is lamentable, since well-controllable hydrodynamics are essential to both biopharmaceutical simulations and quality control. Here, we focus the discussion on the paddle and the basket apparatus, since these are the most important and widely used for oral solid dosage forms. A brief treatise on the hydrodynamics of the flow-through apparatus completes this section. 

Dissolution was carried out with the paddle method according to USP XXI, using a Prolabo dissolution tester. The dissolution medium was 1000 ml of distilled water at 37 0.5°C and 50 rev min-1. At appropriate time intervals, 5 ml of sample was withdrawn and an equal volume of medium was added to maintain a constant volume. Sample were filtered, diluted with lithium carbonate solution as an internal standard, and analysed using a Dr Lange MD 70 flame photometer. Each dissolution profile is the average of six separate tablets. 

Operational Qualification The OQ document certifies that the equipment works as desired and defined by the manufacturer and the purchaser. An example is the acquisition of a new high-shear mixer/granulator where the paddle is put on rotation with a real calibrated rotation speed tester and, if the value obtained meets the specifications, the mixer paddle rotation passes the OQ test. If not, additional requalification must be performed. All the test results must be introduced and verified in the OQ report that is approved by the company at the end. The OQ document must describe several tests and related specifications to perform on the equipment in order to evaluate if it is working well, and the test to be performed must be described and approved by the manufacturer and the purchaser. Therefore, tests must be performed on the equipment, and for each one a description and signature of who performed and verified the test are required. Usually the tests are performed by the manufacturer and verified by the purchaser. These tests usually consist of evaluating if the mechanical and electric components of the equipment are working as desired. 

When dealing with small volumes, a fairly common approach has been to take the glass vessel and reduce its size to 100-200 mL, and to also scale down the size of the paddle shaft or basket shaft and baskets accordingly (Fig. 11.1). In most cases, the modified and smaller vessels are configured within the standard dissolution tester. Table 11.1 provides a comparison between standard USP dissolution Apparatus 2 and minidissolution assembly. Because the minidissolution assembly is not compendial, chemical and mechanical calibration procedures should be developed for performance verification. 

In the rotating disk apparatus, the die is then inverted and screwed onto a customized shaft on a dissolution tester, which is then lowered into the dissolution medium until the face pellet is 3.8 cm from the bottom of the vessel. The shaft is then rotated in the same way as USP Apparatus 1 and 2. In the stationary disk apparatus, the die containing compressed pellet is placed face up into a flat-bottomed dissolution vessel prefilled with the appropriate volume of dissolution medium. The medium is stirred by means of a rotating paddle (e.g., USP Apparatus 2) positioned 6 mm above the pellet surface. 

An alternative procedure, to ensure no external force is applied to the powder bed by the vaned paddle, is to place the compacted sample on a balance and when the paddle is immersed in the powder to raise the vaned head slowly until the balance reading is zero. This dynamic method of bulk powder characterisation is allied to the rheological method for measurement of the viscosity of non-Newtonian fluids and suspensions. Commercial instruments based on the WSL cohesion tester are now available in the form of the FT4 Powder Rheometer (Freeman Technology) and the Stable Micro Systems Powder Flow Analyser (Stable Micro Systems). 

The EIA system was coupled with a paddle dissolution tester equipped with a dissolution vessel in a thermostated water bath. A stainless steel tube (0.5 mm i.d.) for sampling was connected to the EIA system by a polyethylene tube whose end was fixed between the surface of the dissolution fluid and the end of the paddle. 

---