Rotating basket method

Figure 1 Rotating basket method. Source From Ref. 10.

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.

Dissolution testing of indapamide is accomplished using the rotating basket method (USP Method I) with 900 mL of simulated gastric fluid T.S. without enzymes heated to 37<>C as the dissolution medium and a basket rotation of 100 rpm. Samples are placed in the baskets and the baskets are then lowered into the dissolution medium with samples withdrawn at appropriate intervals. The samples are filtered through 0.45 pm Miilipore filters. The dissolution medium is assayed for indapamide against appropriate standards using an UV absorbance assay (23). 

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. 

Fig. 5.15 Release of 5 6)-carboxyfluorescein from chitosan capsules, determined by the J.P. rotating basket method. Key ( ) liquid 1 (j. P.) liquid 2 (j.P.) 33% suspension of cecal contents (O) phosphate-buffered saline (pH 6.0). Results are expressed as the mean+SE of two to four experiments.

Dissolution tests were performed with the rotation basket method, with 900 ml of 57 water at 50-100 rpm, according to USP XX and XXI. / /. he dissolved pharmacon content was measured spectrophotometrically /Spektromom 195 instrument/ and the CD content was measured in solution with concentrated sulphuric acid and anthrone at 625 nm /8/. 

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. 

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. 

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.

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 release tests were performed using the USP dissolution method (apparatus I) and utilized 1000 ml of pH 1.2 simulated gastric fluid (USP XXI) or pH 6.8 simulated intestinal fluid (USP XXI) without enzymes, equilibrated to 37°C and stirred with the basket rotating at 50 or 150 rev/ min. Drug concentrations were assayed by UV spectrophotometry at 255 nm. The experiments were continued until 100% dissolution was achieved. The release data were analysed to zero order, calculating the slope and intercept of the line. Each data point is the average of six individual determinations. In all cases the standard deviation was less than 9%. 

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. 

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