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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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Change of d(0.1), d(0.5), and d(0.9) of API particle size distributions over milling time. Reference values belong to raw meloxicam.
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fig3: Change of d(0.1), d(0.5), and d(0.9) of API particle size distributions over milling time. Reference values belong to raw meloxicam.

Mentions: Tablets ME Tbl 2 were prepared by the compression of granules and were used for experiments. An adverse phenomenon of the mechanical method is gradual destruction of particles over the milling time. Figure 3 shows the change of d-values of meloxicam particle size distributions over milling time. Reference values of raw meloxicam were measured before formulation into tablets. Minimal change (approximately 5 percent) of d-values was observed at 0.5 min milling time. The rapid decrease of particle size was observed if the milling time was longer than 0.5 min.


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

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

Change of d(0.1), d(0.5), and d(0.9) of API particle size distributions over milling time. Reference values belong to raw meloxicam.
© Copyright Policy
Related In: Results  -  Collection

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

fig3: Change of d(0.1), d(0.5), and d(0.9) of API particle size distributions over milling time. Reference values belong to raw meloxicam.
Mentions: Tablets ME Tbl 2 were prepared by the compression of granules and were used for experiments. An adverse phenomenon of the mechanical method is gradual destruction of particles over the milling time. Figure 3 shows the change of d-values of meloxicam particle size distributions over milling time. Reference values of raw meloxicam were measured before formulation into tablets. Minimal change (approximately 5 percent) of d-values was observed at 0.5 min milling time. The rapid decrease of particle size was observed if the milling time was longer than 0.5 min.

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