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Hot-stage microscopy for determination of API particles in a formulated tablet.

Simek M, Grünwaldová V, Kratochvíl B - Biomed Res Int (2014)

Bottom Line: In each case, hot-stage micrographs, taken before and after the API melting point, were compared with image analysis software to obtain the PSDs.Then, the PSDs of the APIs from the disintegrated tablets were compared with the PSDs of raw APIs.Good agreement was obtained, thereby confirming the robustness of our methodology.

View Article: PubMed Central - PubMed

Affiliation: Department of Solid State Chemistry, Institute of Chemical Technology Prague, Technická 5, 166 28 Prague, Czech Republic.

ABSTRACT
Although methods exist to readily determine the particle size distribution (PSD) of an active pharmaceutical ingredient (API) before its formulation into a final product, the primary challenge is to develop a method to determine the PSD of APIs in a finished tablet. To address the limitations of existing PSD methods, we used hot-stage microscopy to observe tablet disintegration during temperature change and, thus, reveal the API particles in a tablet. Both mechanical and liquid disintegration were evaluated after we had identified optimum milling time for mechanical disintegration and optimum volume of water for liquid disintegration. In each case, hot-stage micrographs, taken before and after the API melting point, were compared with image analysis software to obtain the PSDs. Then, the PSDs of the APIs from the disintegrated tablets were compared with the PSDs of raw APIs. Good agreement was obtained, thereby confirming the robustness of our methodology. The availability of such a method equips pharmaceutical scientists with an in vitro assessment method that will more reliably determine the PSD of active substances in finished tablets.

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Results of meloxicam PSD in generic drug (ME Tbl 1) obtained by hot-stage microscopy and by FTIR mapping.
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fig6: Results of meloxicam PSD in generic drug (ME Tbl 1) obtained by hot-stage microscopy and by FTIR mapping.

Mentions: The preparation of tablet cut is described in our previous publication [10]. FTIR map of the microtome cut of ME Tbl 1 tablet is shown in Figure 5. FTIR mapping presents “domains” of all components (meloxicam—black, Avicel PH102—dark grey, lactose—light grey, and crospovidone—white). Image analysis results of meloxicam PSD, obtained from FTIR mapping and hot-stage microscopy, are compared in Figure 6. A lot of API “domains” from FTIR map are much bigger than particles analyzed with hot-stage microscopy which provides congruent results with reference PSD of meloxicam. FTIR mapping does not seem to be suitable for an API PSD assessment. On the other hand, comparison of FTIR map with hot-stage microscopy allows the determination of API agglomerates in a tablet.


Hot-stage microscopy for determination of API particles in a formulated tablet.

Simek M, Grünwaldová V, Kratochvíl B - Biomed Res Int (2014)

Results of meloxicam PSD in generic drug (ME Tbl 1) obtained by hot-stage microscopy and by FTIR mapping.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4127278&req=5

fig6: Results of meloxicam PSD in generic drug (ME Tbl 1) obtained by hot-stage microscopy and by FTIR mapping.
Mentions: The preparation of tablet cut is described in our previous publication [10]. FTIR map of the microtome cut of ME Tbl 1 tablet is shown in Figure 5. FTIR mapping presents “domains” of all components (meloxicam—black, Avicel PH102—dark grey, lactose—light grey, and crospovidone—white). Image analysis results of meloxicam PSD, obtained from FTIR mapping and hot-stage microscopy, are compared in Figure 6. A lot of API “domains” from FTIR map are much bigger than particles analyzed with hot-stage microscopy which provides congruent results with reference PSD of meloxicam. FTIR mapping does not seem to be suitable for an API PSD assessment. On the other hand, comparison of FTIR map with hot-stage microscopy allows the determination of API agglomerates in a tablet.

Bottom Line: In each case, hot-stage micrographs, taken before and after the API melting point, were compared with image analysis software to obtain the PSDs.Then, the PSDs of the APIs from the disintegrated tablets were compared with the PSDs of raw APIs.Good agreement was obtained, thereby confirming the robustness of our methodology.

View Article: PubMed Central - PubMed

Affiliation: Department of Solid State Chemistry, Institute of Chemical Technology Prague, Technická 5, 166 28 Prague, Czech Republic.

ABSTRACT
Although methods exist to readily determine the particle size distribution (PSD) of an active pharmaceutical ingredient (API) before its formulation into a final product, the primary challenge is to develop a method to determine the PSD of APIs in a finished tablet. To address the limitations of existing PSD methods, we used hot-stage microscopy to observe tablet disintegration during temperature change and, thus, reveal the API particles in a tablet. Both mechanical and liquid disintegration were evaluated after we had identified optimum milling time for mechanical disintegration and optimum volume of water for liquid disintegration. In each case, hot-stage micrographs, taken before and after the API melting point, were compared with image analysis software to obtain the PSDs. Then, the PSDs of the APIs from the disintegrated tablets were compared with the PSDs of raw APIs. Good agreement was obtained, thereby confirming the robustness of our methodology. The availability of such a method equips pharmaceutical scientists with an in vitro assessment method that will more reliably determine the PSD of active substances in finished tablets.

Show MeSH
Related in: MedlinePlus