Dissolution tests paddle method

The USP Dissolution General Chapter < 711 > describes the basket (Apparatus 1) and paddle (Apparatus 2) in detail. There are certain variations in usage of the apparatus that occur in the industry and are allowed with proper validation. The literature contains a recommendation for a new USP general chapter for dissolution testing (6). In this article, guidance for method validation and selection of equipment is described. It may be a useful guide when showing equipment equivalence to compendial equipment. 

Fluid velocities using the basket method were determined to range between 0.3 and 5 cm/sec [25-200 rpm], and for the paddle method, between 1.8 and 37 cm/sec [25— 200 rpm]. Possible applications of these fluid velocity data may include their use to forecast in vitro dissolution rates and profiles of pure drug compounds for the paddle test employing an appropriate mathematical scenario/formula like the combination model. 

Solid oral dosage forms containing new chemical entities (NCEs) are commonly formulated into tablets or capsules as their first market image formulation. Subsequent drug product line extension development on these NCEs may evaluate more specialized drug delivery systems. Dissolution testing of standard oral tablets or capsules will commonly utilize the paddle or basket apparatus. In this chapter we focus primarily on the development and subsequent validation of dissolution testing methods that use these two devices. 

Rotational Speed. The rotational speed of a basket or paddle is an important consideration in the development and validation of the dissolution test. A speed of 100 rpm is commonly used with the basket apparatus and a speed of 50 rpm is used with paddles. In method validation, one needs to ensure that slight variations in rotational speed will not affect the outcome of the dissolution test. The compendial limit for variations in rotational speed is 4%, but a wider variation (e.g., 10%) may be considered in testing the robustness of the method. 

USP Apparatus 1 (rotating basket) and 2 (paddle) are the first choices when developing a dissolution method for solid oral dosage forms. Even though the compendial equipment may not be suitable for all low-dose drug products, a brief discussion of these apparatuses is necessary in order to understand the basic operation of dissolution testing. 

To compare the in vivo absorption profile as presented in Fig. 6 with in vitro data, an in vitro profile must be obtained. Various in vitro dissolution tests exist. Any method which can discriminate between the formulations can be used but certain techniques tend to be preferred, i.e., paddle, flow through cell, and basket (USPII, IV, I). In addition, aqueous media is preferred (pH not exceeding 6.8 or 7.2) the addition of surfactant is possible for poorly soluble drugs. Some media are... 

Figure 12.2 The rotating basket and rotating paddle versions of the official method for dissolution testing of solid oral dosage forms, (a) The rotating basket - method 1, USP/NF. This method is official for USP/NF and BP. Current specifications describing geometry and positions for each compendium are shown, (b) The rotating paddle - method 2, USP/NF.

As a general guideline in the choice of dissolution test apparatus, the simplest and most well-established method should be chosen, with respect to both in-house know-how and regulatory aspects. In most cases, this is the USP II paddle method or the USP I rotating basket method. However, if satisfactory performance cannot be obtained by these methods, others should be considered. Primarily, the USP III and USP IV methods, and non-compendial methods could also provide relevant advantages. 

Dissolution tests using the basket method (50/100 rpm) or the paddle method (50/75 rpm) under mild test conditions are used to generate a dissolution profile at 15-minute intervals. The pH range is 1.2-6.8 pH up to 8.0 may be tested with justification. The temperature is 37 0.5 °C. Methods are described in the US Pharmacopoeia. Test requirements vary depending on solubility of drug products. In vitro test may need validation to confirm in vivo results. 

Sample preparation is critical for dissolution testing. Tablets or capsules may be placed in a sinker when using USP Apparatus 2 (paddle method). If USP Apparatus 1 (basket method) is used, then the baskets should be dry when samples are placed in them. 

The general monographs for capsules, tablets and suppositories refer to the dissolution test when relevant. The Ph. Eur. describes for capsules and tablets different equipment, most important variants being the paddle-method and the basket-method. Next to these the flowthrough-cell method is described, especially intended for the determination of the dissolution rate of poorly soluble substances. 

For the determination of dissolution profiles of the samples the rotating-paddle method of USP 23 at 100 rpm was used (PTW2 dissolution test apparatus, Pharmatest Apparatebau, Hamburg). The studies were conducted in 900 ml dissolution media. The dissolution of potassium chloride was continuously monitored with a digital pH meter (Radelkis OP 211/1, Budapest), equipped with a chloride-selective electrode. 

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