Rotating paddle method

In this study, the influence of several formulation factors on the release kinetics of potassium chloride from directly compressed matrices is investigated. Formulations containing hydrophilic (methylcellulose, carbomer), plastic (polyvinyl chloride) and wax (glycerol palmitostearate) matrix materials at concentrations of 10%, 15% and 20%, and insoluble excipients, were prepared and tested using the USP XXI-NF XVI rotating paddle method. 

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.

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. 

Momentum Methods. Density can be measured by several momentum methods. The density of the fluid is obtained by measuring fluid flow rate and fluid flow momentum. For example, the rotating paddle method is based on the principle that an aerodynamic foil, if rotated through a fluid, will experience a measurable drag, which can be related to density. The rotating paddle serves both as a density measurement device and as a stirrer for the mixture. The equipment required is relatively simple. Disadvantages include low frequency response and sensitivity, and the presence of moving parts in the fluid. 

Density of a fluid can also be measured by the angular momentum method, which measures the angular momentum of a rotating fluid and relates this momentum to density. As in the rotating paddle method, the angular momentum method measures the density and stirs the mixture. The equipment required could be relatively simple. Disadvantages of this method include the presence of bulky, moving parts in the fluid and the lack of any... 

In the paddle method, bulk Reynolds numbers range from Re = 2292 (25 rpm, 900 mL) up to Re = 31025 (200 rpm, 500 mL). In contrast, Reynolds numbers employing the basket apparatus range from Re = 231 to Re = 4541. These Reynolds numbers are derived from dissolution experiments in which oxygen was the solute [(10), Chapter 13.4.8] and illustrate that turbulent flow patterns may occur within the bulk medium, namely for flow close to the liquid surface of the dissolution medium. The numbers are valid provided that the whole liquid surface rotates. According to Levich (9), the onset of turbulent bulk flow under these conditions can then be assumed at Re 1500. 

The results of this study confirmed the appropriateness of the paddle height (2.5 cm above the bottom of the vessel), paddle speed (100 rpm) and sampling zone (midway between the surface of the medium and the top of the rotating paddle, not less than 1 cm from the vessel wall) used in the tablet method. 

FIGURE 12 Various drag dissolution methodologies, (a) In the paddle method, the tablet is placed in the dissolution vessel containing dissolution medium and the paddle is rotated at defined rpm, while the dissolution vessel is maintained at body temperature, (b) In the basket method, the tablet is kept inside a meshed basket and rotated, (c) For IDR studies, the tablet is kept inside a die cavity and only one face of the tablet is exposed to the dissolution medium. 

Fig. 11 Dissolution profiles of diltiazem hydrochloride from a swelling matrix system in phosphate buffer pH 6.8 at 37 °C using the basket and paddle methods rotating at 50, 75, and 100 rpm.

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. 

ASTM D 7226. 2011. Test method for determining the viscosity of emulsified asphalts using a rotational paddle viscometer. West Conshohocken, PA ASTM International. 

A number of investigators have measured the apparent viscosity of fluidized bed using methods available for ordinary liquids. For example, Matheson et al. (1949) and Furukawa and Ohmae (1958) employed a rotating paddle viscometer and found that a fully fluidized bed had a viscosity from 0.5 to 20 poises. The viscosity increases with the size of the particles in the bed. Other researchers, Kramers (1951), Dickman and Forsythe (1953), and Schugerl et al. (1961), used viscometers of slightly different designs and obtained practically similar results. For small shear stress, the fully fluidized beds behave as newtonian fluids. The viscosity of the fluidized bed is very high at close to minimum fluidization condition and decreases sharply with increases in gas flow. 

Density measurements are closely akin to liquid level measurements because both are often required simultaneously to establish the mass contents of a tank, and the same physical principle may often be used for either measurement. Thus, the methods of density determination include the techniques of direct weighing, buoyancy, differential pressure, capacitance, optical, acoustic, ultrasonic, momentum, rotating paddle, transverse momentum, nuclear radiation attenuation, and nuclear magnetic resonance. Each of the principles involved will be discussed along with its relative merits and shortcomings. 

Figure 10 Rotational (tangential) flow (UA) as a function of stirring rate (co) for paddle (filled circles) and basket (open circles) Mean SD position S2 approximately 1 cm above the paddle and midway between the paddle shaft and the wall of the dissolution vessel. (Please note that, in contrast to simulation techniques such as, for instance, computational fluid dynamics, these data are based on dissolution experiments.) Source Data from Ref. 10, UPE method.

When the basket apparatus is used, the sample is placed in the dry basket the basket fitted to the coupling disk and lowered to the position specified, and rotation is started immediately. When the paddle apparatus is used, the sample is allowed to sink to the bottom of the vessel, and rotation of the paddle started immediately at the speed specified. If use of the sinker is required, the sample is placed in the sinker and allowed to sink to the bottom of the vessel. The samples are collected at the appropriate time, filtered by a suitable method, and the filtrate used as the sample solution. The drug substance(s) in the sample solution is assayed, and the quantity dissolved at the specified time is expressed as a percentage of the labeled amount. 

The requirements for the basket and paddle apparatus described by the three major pharmacopoeias is generally similar but do have some unique differences. These general requirements are summarized in Table 4.2. It is important to know these differences at the time of method development and dissolution. Some of these characteristics are utilized as a system check in the regular performance verification of the dissolution apparatus (e.g., shaft position, shaft rotation variation, and distance of bottom of apparatus to inside bottom of vessel). 

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. 

Mechanical Methods Static or rotating breaker bars or slowly revolving paddles are sometimes successful. Their application in conjunction with other methods is frequently better. As indicated in the theory of foams, they will work better if installed at a level at which the foam has had some time to age and drain. A rotating breaker works by deforming the foam, which causes rupture of the lamella walls. Rapidly moving slingers will throw the foam against the vessel wall and may cause impact on other foam outside the envelope of the... 

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. 

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