Determining Potency of Preclinical Dose Formulations - Pharmaceutical Technology

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Determining Potency of Preclinical Dose Formulations
Multiple factors arising during sample preparation can affect potency measurements.


Pharmaceutical Technology
Volume 36, Issue 10, pp. 132-134

Laboratory equipment


Table III: Recovery when sample was prepared in plastic versus glass.
Another factor to consider in achieving accurate potency is the effect of laboratory glassware and/or equipment. Interactions may occur between the analyte and surface of the volumetric flask used. Such an observation was discovered in preparation of samples in plastic versus glass (see Table III).

Solutions were left in plastic for 30 minutes. As demonstrated, the analyte possessed a high affinity for plastic. Furthermore, an assessment made using a glass serological pipette yielded higher recoveries, as compared with using a positive displacement pipette containing a plastic tip.

Filtration

Filtration is an effective method for removing impurities from a solution; however, if the correct pore size and/or media are not used, the analyte may be removed along with the impurities. An experiment was conducted on a clear, colorless solution. The solution was filtered through a 0.22 m polyvinylidene fluoride (PVDF) syringe filter, and analyzed prefiltration and postfiltration. At low and high levels, the prefiltered solution had an average percent recovery of 97.1% and 97.7%, respectively. Postfiltered samples had 0% recovery at both low and high concentrations because the analyte was removed by the filter.

Compound characteristics

If potency issues exist after assessing most potential mixing complications, it is important to refer back to the compound characteristics. If a compound is micronized, problematic weighing may exist because of the static, cohesiveness, and/or lightness of the material. Alternatively, the material may be highly hygroscopic and require the use of a desiccant in storage. When weighing a hygroscopic material, it is essential to consider the amount of water being absorbed, as this can cause uncertainty during the weighing process. It is also significant to account for a correction factor in consideration of salt factors and purity. This is important when considering manufactured lots used for in vivo studies that do not undergo purification processes that are performed for clinical trials.

Storage

A final factor in achieving correct potency is a consideration of storage and stability of the formulated compound. It is necessary to have data to support conditions and duration of storage. Degradation of a compound can be seen at different temperature conditions (e.g., ambient, refrigerated, frozen or ultra-frozen). Yellow light versus ambient light may also affect potency if the formulated test article requires protection from light. Analysis of potency of a formulated drug in specified storage conditions, extending longer than the dose formulation, should be performed before dosing. Covering the time window from preparation to dosing ensures that the proper potency of drug is delivered to the test system.

Conclusion

Potency of a dose formulation is an essential and crucial component in ensuring that the test system receives the appropriate amount of active ingredient based on predetermined specifications. If the correct potency is not achieved, the toxicological effects of the drug may not be observed. Failure to achieve accurate potency levels may be affected by many factors including weighing and mixing procedures, use of laboratory equipment, filtration, and even compound characteristics and storage. When these problems occur, it is important to isolate and investigate each variable to identify the root cause.

Ashley Sanchez is an ssociate scientist, Melissa Whitsel is analytical manager, and Amy Smith is director of Analytical Laboratory Operations, all at MPI Research, Mattawan, MI.

References

Code of Federal Regulations Title 21, Food and Drugs (Govenment Printing Office, Washington DC), Part 58.

M. Whitmire et al., The AAPS Journal, 12 (4), 628–634 (2010).


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