Dissolution sampling time

Key operating parameters that may change (or be optimized) throughout a product s development and approval cycle are dissolution sampling time points and dissolution limits or specifications by which the dissolution results should be evaluated. The results generated from the dissolution test need to be evaluated and interpreted based on the intended purpose of the test. If the test is used for batch-to-batch control, the results should be evaluated in regard to the established limits or specification value. If the test is being utilized as a characterization test (i.e., biopharmaceutical evaluations, formulation development studies, etc.) the results are usually evaluated by profile comparisons. 

An f value between 50 and 100 suggests the two dissolution profiles are similar. Also, the 2 average difference at any dissolution sampling time point... 

The dissolution sampling times for both multisource and comparator product profiles should be the same ... 

Therefore, the development and validation of a scientifically sound dissolution method requires the selection of key method parameters that provide accurate, reproducible data that are appropriate for the intended application of the methodology. It is important to note that while more extensive dissolution methodologies may be required for bioequivalency evaluations or biowaivers (i.e., multiple media, more complex dissolution media additives, and multiple sampling time points), it is also essential for the simplified, routine quality control dissolution method to discriminate batch-to-batch differences that might affect the product s in vivo performance. 

Functions to validate on automated dissolution systems may include bath operation, balance operation, media dispensing operations, media removal, sampling operations, media replacement, thermistor operation, robot operation, sample timing, sequence, and dilution. 

FIGURE I Typical fast HPLC chromatograms for a set of three dissolution samples at three time points. 

Filters are required for dissolution sample collection. It is necessary to filter out the excipents that may cause interference in sample analysis. Appropriate recovery studies should be performed and documented. Any observed bias should be addressed. Filtration must be performed when the sample aliquots are withdrawn, not at a later time. 

HPLC methods are preferred if excipients would interfere, if nonspecific detection techniques (mainly in UV) would be used, or when multiple APIs (combination product) are present in a drug product. Since dissolution sample set analysis can be very long due to six samples per bath as well as multiple time points for prohle testing, fast run times are preferred to quickly determine the results. If a fast HPLC method for CU is available, then the identical HPLC method can be utilized for dissolution analysis. 

Minerals usually dissolve incongruently during the initial stages of the dissolution process. In this case, Ca is released from wollastonite faster than Si. In addition, the rate of both Ca and Si declines with increasing extent of reaction. Eventually the difference between release rates, as well as the change in the rates, from one sample time to the next becomes smaller than the resolution of the rate measurements. When both of these conditions exist the rates are assumed to represent the dissolution rate that is appropriate for long-term geochemical processes. 

The Ph. Eur. specifies (for information only and so not compulsory) that about the determination of the dissolution of a capsule or tablet the following points should be recorded type of equipment composition, volume and temperature of the dissolution medium, rotation speed, sampling times, sample volume and sampling method, method of analysis, acceptance criteria. 

I go through the progress of DNP in the last year in that order. Donovan et al described experiments in which both and H in a sample were sequentially hyperpolarized under ciyogenic conditions. After rapid dissolution of the sample, time-dependent polarization gains, persistent on the time scale of were observed for protons bound to The... 

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