Dissolution vessel

A very powerful method for the evaluation of solubility differences between polymorphs or solvates is that of intrinsic dissolution, which entails measurements of the rates of solution. One method for this work is to simply pour loose powder into a dissolution vessel, and to monitor the concentration of dissolved solute as a function of time. However, data obtained by this method are not readily interpretable unless they are corrected by factors relating to the surface area or particle size distribution of the powder. In the other approach, the material to be studied is filled into the cavity of a circular dissolution die, compressed until it exhibits the effective planar surface area of the circular disc, and then the dissolution rate is monitored off the surface of the rotating disc in the die [130],... 

Pressure dissolution and digestion bombs have been used to dissolve samples for which wet digestion is unsuitable. In this technique the sample is placed in a pressure dissolution vessel with a suitable mixture of acids and the combination of temperature and pressure effects dissolution of the sample. This technique is particularly useful for the analysis of volatile elements which may be lost in an open digestion [24]. 

A typical production unit consists of an acid-proof diazotization kettle ( diazo-tizer ), a dissolution vessel to dissolve the coupling component in its medium, and a reaction vessel with an agitator, in which the coupling reaction is carried out. Typ-... 

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.

Figure 12 Schematic flow pattern for the basket apparatus. Because of the hemispheric symmetry of the dissolution vessel, it is sufficient to draw the flow just for one-half of the vessel. The arrows indicate flow direction. All designated flow patterns are based on quantitative experimental data. Source From Ref. 10.

Rotational fluid velocities are calculated since horizontal (rotational) flow prevails in the hydrodynamic regime within the dissolution vessels. Thus, the overall hydrodynamics and hence dissolution is dominated by the substantially higher rotational (tangential) fluid velocities. 

In vitro dissolution data can be collected in closed systems (e.g., in compendial dissolution vessels) or by using open (flow-through) systems (1). 

In comparison to the approach of Ginski et al. [48], the Miyazaki s method appears to be more elaborate and complex and is thus coming closer to the in vivo situation. The device can simulate various effects of pH on dissolution and is, as an open system, closer to in vivo conditions compared to a closed one. However, it exhibits the drawback of not freely adjustable pH values acting on the drug. Low flow rate in the dissolution vessel may limit applications of complete dosage forms and allows predominantly only the use of granules, pellets, or grinded tablets. Furthermore, the application of compendial dissolution devices appears to be a more robust approach. 

A dissolution testing apparams consists of a set of six or eight thermostatted, stirred vessels of an established geometry and volume from the USP guidelines. The dissolution apparatus provides a means to dissolve each sample, but does not provide a means to determine the concentration of the aetive ingredient in the bath. In the most well-established scheme, sipper tubes withdraw samples from each dissolution vessel and send them through a multiport valve to a flow cell sitting in the sample chamber of a UV-vis spectrophotometer. In recent years, moves have been made to make in situ measurements in the dissolution baths by means of fiber-optic probes. There are three possible probe implementations in situ, down shaft, and removable in situ (see Table 4.2). 

Two experiments were performed to vahdate the immediate-release component and the sustained-release component. To vahdate the sustained-release component, the equivalent of one tablet weight of placebo blend and 100% label claim (LC) of the immediate-release drug substance were added to 900 ml of deionized water at 37°C in each of six dissolution vessels. The sustained-release drug substance was added to vessels 1 through 6 in increments from 10% to 120% LC. Ahquots were removed, filtered and stored for further HPLC analysis. 

Dissolution vessel Nominal capacity = 1, 2, or 4L Nominal capacity of 1 L Nominal capacity of 1 L... 

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. 

Accuracy. Sample solutions of known concentration (e.g., spiked placebo) are used for the accuracy determination. Experimental work may be organized so that the same stock solutions are used to prepare both linearity and accuracy solutions. The accuracy solution must be exposed to normal test conditions (e.g., mixing in a heated dissolution vessel). Determine any bias that is caused by the sampling and analysis of the solutions. If a dissolution profile of the drug product is required, accuracy determinations at different concentrations of the required profile will need to be performed (e.g., at 40, 75, and 110% of theoretical release). The results are reported as percent theory. 

Buegelsdijk et al. described a fully automated system for preparation of dissolved Pu metal samples using the Zymate II (Zymark Corporation) laboratory robot.67 The sample preparation steps included bar-code label reading, weighing the sample, and transfer to the dissolution vessel. 

Reducing dissolution vessel volume is one of the simple approaches for equipment manufacturers to help overcome the problem of low dmg concentrations for low-dose products. Many apparatuses modified to small volume dissolution vessels are now commercially available. A list of manufacturers for these special apparatuses is provided below ... 

Scott P. 2005. Geometric irregularities common to the dissolution vessel. Dissolution Technol. 12 18-21. 

Liddell MR, Deng G, Huack WW, Brown WE, Wahab SZ, Manning RG. 2007. Evaluation of glass dissolution vessel dimensions and irregularities. Dissolution Technol. 14 28-34. 

Fig. 8. Diagram of a two-vessel crystalliser. C, Single crystal Hi, H2, and H3, heating elements M, magnetic stirrer P, pump PC, polycrystalline material T1 and T2, thermometers, typically Hg in glass or platinum resistance thermometers (PRT), T1 is used to control heaters T3 and T4, miniature thermometers, i.e. thermister or PRT VI, crystallisation vessel V2, dissolution vessel.

Minimum quantities of acids are needed if dissolution is carried out in a PTFE pressure dissolution vessel which is capable of operating at temperatures up to 180° C. With organic matrices, however, only the special versions of this apparatus capable of withstanding very high pressures should be used. For completely inorganic dissolutions, there is also an all-PTFE vessel, which is limited to temperatures below 120° C, but which completely removes the risk of contamination from the metal outer-casing. 

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. 

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