Dissolution apparatus Paddle

Visual Observation Method Each sample of microspheres is placed into 500 ml of simulated gastric fluid (SGF, pH 1.2, without enzymes) filled in basket-type dissolution apparatus. Paddle rotation speed is set at 100 rpm, temperature is to be maintained at 37°C 0.5°C. The number of floating microspheres has to be counted visually after 24 h. The percentage of floating microspheres was calculated according to the following equation ... 

In the meantime, dissolution testing was more and more standardized and gained enormous impact on the fields of quality assurance and drug development in pharmaceutical industry. Several dissolution apparatus made then-way into the pharmacopoeiae, such as the rotating paddle, rotating bas-... 

McCarthy LG, Kosiol C, Healy AM, Bradley G, Sexton JC, Corrigan OI. Simulating the hydrodynamic conditions in the United States Pharmacopeia paddle dissolution apparatus. AAPS Pharm Sci Tech 2003 4(2) Article 22. McCarthy LG, Bradley G, Sexton JC, Corrigan OI, Healy AM. Computational fluid dynamics modeling of the paddle dissolution apparatus agitation rate, mixing patterns, and fluid velocities. AAPS Pharm Sci Tech 2004 5(2) Article 31. 

Six tablets were subjected to. dissolution using the USP dissolution apparatus (Vanderkamp 600, Van-Kel Ind., NJ, USA) in 500 ml buffer pH 1.2 (the first hour) and 650 ml buffer pH 6.8 (1-14 h), maintained at 37°C and rotated with paddles at 50 rev min-1 (first hour) and 130 rev min-1 (1-14 h). The dissolution apparatus was connected to a UV-visible spectrophotometer (Uvikon 810, Roxche Bioelectronique Kontron, Marseille) and a computer (VAX 780 Digital). The absorbance of the dissolution medium at 275 nm was recorded automatically at intervals (1, 2, 4, 5, 8, 10, 12 and 14 h). The percentage of the drug released was calculated and the corresponding release profiles were obtained. 

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). 

USP Dissolution Apparatus 1 (basket) and 2 (paddle) are commonly used for immediate-release formulations. USP Apparatus 3 (reciprocating cylinders) is the system of choice for testing extended-release products or a dosage form that requires release profiling at multiple pH levels and time points. Low-dose products may require the use of flow-through analysis or other low-volume test techniques (noncompendial 100- or 200-mL dissolution vessels). Once the apparatus is selected and has been shown to be suitable during method development, no further evaluation of another apparatus is required during validation. 

The preferred dissolution apparatus is 1 ISP apparatus 1 (basket) or 11 (paddle), used at compendially recognized rotation speeds (e.g., 100 rpm for the basket and 50-75 rpm for the paddle). In other cases, the dissolution properties of some ER formulations may be detennined with USP apparatus 111 (reciprocating cylinder) or IV (flow through cell). 

For immediate-release products, the most commonly used dissolution apparatus are the USP Apparatus 1 (basket) and USP Apparatus 2 (paddle). Usually, the Apparatus 1 is operated at 100 rpm and the Apparatus 2 at 50 rpm. However, it was suggested that the Apparatus 2 is operated at 75 rpm... 

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. 

Numerous dissolution methods (not limited to those officially prescribed) must be available to ensure proper discrimination as well as the use of various media. The preferred dissolution apparatus is USP I (basket), II (paddle), or IV (flow through cell). USP apparatus III (reciprocating cylinder) could be considered in some cases. An aqueous medium, either water or a buffered solution preferably not exceeding pH 6.8 (or 7.2), is recommended, other pH must be justified. For poorly soluble drugs, the addition of a surfactant may be necessary. 

Fig. 4 Schematic of USP drug dissolution apparatuses 1 (basket) and 2 (paddle). (From Qureshi, S.A. Calibration the USP dissolution apparatus suitability test. Drug Inf. J. 1996, 30, 1060, Fig. 2.)...

Sheng, J.J., Sirois, P.J., Dressman, J.B. and Amidon, G.L. (2008) Particle diffusional layer thickness in a USP dissolution apparatus II a combined function of particle size and paddle speed. Journal of Pharmaceutical Sciences, in press. 

Figure 7.2 Standard and modified Cpeak vessel) USP II dissolution apparatuses including illustrations of the different flow patterns within the beakers and photographs taken at a paddle stirring rate of 100 rpm showing a heap of pellets beneath the paddle in the standard method compared to the desirable dispersion of pellets in the modified method.

Standard USP or BP dissolution apparatus has been used to study in vitro release profiles using rotating elements, paddle, and basket. Dissolution medium used for the study varied from 100 to 500 nd and speed of rotation from 50 to 100 rpm. 

The USP also lists three other dissolution apparatus for transdermal delivery systems, apparatus 5 (paddle over disk), apparatus 6 (cylinder), and apparatus 7 (reciprocating holder). 

The dissolution rate studies of carvedilol alone and its spherical agglomerates were performed in triplicate in a dissolution apparatus (Electrolab, India) using the paddle method (USP Type II). Dissolution studies were carried out using 900 ml of O.IN HCl (pH 1.2) at 37 0.5 OC at 50 rpm as per US FDA guidelines (U.S. Food and drug administration [USFDA], 2010 and Bhutani et al., 2007.). 12.5 mg of carvedilol or its equivalent amount of... 

Figure 6. Dissolution profdes of HPMC capsules. Apparatus Paddle, 50 rpm. Stored condition 40°C and 75%RH. initial, one month. A two months.

USP Guidelines for setting Dissolution standards Apparatus 2—Paddle adopted two Calibrator Tablets adopted... 

A common feature of widely used apparatus like the paddle or basket method is their limited volume. Typical volumes used in these systems range from about 500 to 4000 mL, limiting their use for very poorly soluble substances. Theoretically at least, open systems may be operated with infinite volumes to complete the dissolution of even very poorly soluble com-... 

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. 

Close inspection of USP Apparatus 1 and 2 before use can help identify sources of error. Obviously, dimensions should be as specified. In cases of both baskets and paddles, shafts must be straight and true. The paddles are sometimes partially coated with Teflon. This coating can peel and partially shed from the paddle, causing flow disturbance of hydrodynamics within the vessel. Paddles can rust and become nicked or dented this can adversely affect dissolution hydrodynamics and be a source of contamination. Thorough cleaning of the paddles is also important, to preclude carry over of drug or medium. 

Ross MS, Rasis M. Mega paddle—a recommendation to modify Apparatus 2 used in the USP general test for dissolution <711>. Pharm Forum 1998 24(3) 6351-6359. 

For closed dissolution systems, it can be hypothesized that the hydrodynamics depends on the input of energy in a general way. The energy input may be characterized by the power input per unit mass of fluid or the turbulent energy dissipation rate per unit mass of fluid (/ ). Considering various paddle apparatus, the power input per unit mass of fluid (Fig. 3) can be calculated according to Plummer and Wigley [(12), Appendix B, nomenclature adapted] ... 

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. 

Detailed sets of fluid velocity data for the paddle and the basket apparatus, including various positions in the vessels and different volumes (500, 900, and 1000 mL) of dissolution medium, can be found in Ref. 10 (Chapter 11.3). 

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