Dissolution apparatus

The performance of the dmg dehvery system needs to be characterized. The rate of dmg release and the total amount of dmg loaded into a dmg dehvery system can be deterrnined in a dissolution apparatus or in a diffusion ceU. Typically, the dmg is released from the dmg dehvery system into a large volume of solvent, such as water or a buffer solution, that is maintained at constant temperature. The receiver solution is weU stirred to provide sink conditions. Samples from the dissolution bath are assayed periodically. The cumulative amount released is then plotted vs time. The release rate is the slope of this curve. The total dmg released is the value of the cumulative amount released that no longer changes with time. 

The complex situation The analysis involves some instruments (e.g., dissolution apparatus, HPLC, balance), dozens of samples, and several analysts, and could take days to perform. If nobody notices anything particular about the individual snippets of work or any of the results, no observations of probable operator error are documented. When the supervisor then inserts number after unspectacular number into the formula, all results turn out to be within specification limits, with the exception of one or two that are barely outside. But, no documentation, no operator error, just inexplicable OOS, full investigation ... 

Fig. 14 Dissolution-time profiles for a batch-type dissolution apparatus (A), and a continuous-flow dissolution apparatus (B). (Reproduced with permission of the copyright owner, John Wiley and Sons, Inc., from Ref. 1, p. 476.)...

In the 1960s and 1970s, there was a proliferation of dissolution apparatus design. With their diverse design specifications and operating conditions, dissolution curves obtained with them were often not comparable and it was gradually realized that a standardization of methods was needed, which would enable correlation of data obtained with the various test apparatus. As a result, the National... 

The USP 27, NF22 (11) now recognizes seven dissolution apparatus specifically, and describes them and, in some cases allowable modifications, in detail. The choice of the dissolution apparatus should be considered during the development of the dissolution methods, since it can affect the results and the duration of the test. The type of dosage form under investigation is the primary consideration in apparatus selection. 

Figure 4 (a) Assembly for testing timed-release preparations. Redrawn from a letter typewritten on USP paper in 1957. Source From Ref. 23. (b) Continuous flow dissolution apparatus. Source From a 1968 publication by Pemarowski. 

C. During operational qualification the analyst or vendor would assess if the equipment works as specified, generating appropriately documented data. The procedures will verify that the instrument s individual operational units are functioning within a given range or tolerance, reproducibly. For the dissolution apparatus, the water bath temperature and spindle assembly and shaft rpm speed would be obvious operational parameters. 

The dissolution fluid flow characteristics should consist of a predictable pattern that is free of irregularities or variable turbulence. Observations of the product dissolution behavior are critical when choosing a dissolution apparatus. If there are aberrant or highly variable data that can be attributed to the apparatus, then it may be unsuitable for that product. 

Queshi SA, McGilveray IJ. Impact of different deaeration methods on the USP dissolution apparatus suitability test criteria. Pharm Forum 1994 20(6) 8565-8566. 

Rohrs BR. Calibration of the USP 3 [reciprocating cylinder] dissolution apparatus. Dissolution Technol 1997 4(2) 11—18. 

Nicklasson M, Langenbucher F. Description and evaluation of the flow cell dissolution apparatus as an alternative test method for drug release. Pharm Forum 1990 16(3) 532-537. 

Thakker KD, Naik NC, Gray VA, Sun S. Fine-tuning of dissolution apparatus for the apparatus suitability test using the USP dissolution calibrators. Pharm Forum 1980 6(4) 177—185. 

Flow patterns of hydrodynamic systems like the compendial dissolution apparatus may be qualitatively characterized by means of dilute dye injection (e.g., methylene blue) or by techniques using particulate materials such as aluminum powders or polystyrene particles. Flow patterns may be also visualized by taking advantage of density or pH differences within the fluid stream. The Schlieren method, for instance, is based on refraction index measurement. Hot wire anemo-metry is an appropriate method to quantitatively characterize flow rates. The flow rate is proportional to the cooling rate of a thin hot wire presented to the stream. Using laser Doppler... 

The overall situation in vivo is far more complicated than the hydrodynamics in dissolution apparatus. Moreover, only a few... 

General Considerations Using Compendial Dissolution Apparatus to Model GI Passage of MR Dosage Forms... 

Table 1 outlines the current status of scientific development for the dissolution or release testing from various dosage forms and recommends, where possible, the dissolution apparatus of first choice (13). Refer also to Chapter 2 for further description of the USP apparatus. 

Once the appropriate dissolution conditions have been established, the method should be validated for linearity, accuracy, precision, specificity, and robustness/ruggedness. This section will discuss these parameters only in relation to issues unique to dissolution testing. All dissolution testing must be performed on a calibrated dissolution apparatus meeting the mechanical and system suitability standards specified in the appropriate compendia. 

Before describing the various considerations that go into designing a fully automated dissolution apparatus, it may be worthwhile to discuss automation in general for pharmaceutical applications. 

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-... 

The autosampling device is critical to the integrity of automated dissolution testing systems as it serves as the interface between the dissolution apparatus and the sample analysis systems. The autosampler takes... 

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). 

Table 4.2 Probe implementations in fiber-optical dissolution apparatuses...

FIA was used to optimise sampling from a tablet dissolution apparatus in order to determine the rate of release of iron (II) from a sustained release formulation. The dissolution medium was automatically sampled at 30-minute intervals and the 100/rl aliquots of medium were mixed with the iron complexing agent ferrozine, diluted and then passed into a spectrophotometric detector. The system was microprocessor controlled thus enabling unattended sampling of the dissolution medium for a prolonged period."... 

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. 

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