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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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Mixture 1 at 225°C, 275°C, and 300°C temperatures. No change of the system was observed from 25 to 225°C. Methocel melted at 230°C and tadalafil melted at 295°C.
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fig1: Mixture 1 at 225°C, 275°C, and 300°C temperatures. No change of the system was observed from 25 to 225°C. Methocel melted at 230°C and tadalafil melted at 295°C.

Mentions: The principle of API identification is shown on the example of mixture 1 (Figure 1). As tadalafil has higher melting point than Methocel, needle-shaped particles of tadalafil melt later. API particles were identified by comparing pictures taken at 275°C and 300°C as the melting point of tadalafil is 295°C. The experiments were repeated until 600 particles of tadalafil were analyzed.


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

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

Mixture 1 at 225°C, 275°C, and 300°C temperatures. No change of the system was observed from 25 to 225°C. Methocel melted at 230°C and tadalafil melted at 295°C.
© Copyright Policy
Related In: Results  -  Collection

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

fig1: Mixture 1 at 225°C, 275°C, and 300°C temperatures. No change of the system was observed from 25 to 225°C. Methocel melted at 230°C and tadalafil melted at 295°C.
Mentions: The principle of API identification is shown on the example of mixture 1 (Figure 1). As tadalafil has higher melting point than Methocel, needle-shaped particles of tadalafil melt later. API particles were identified by comparing pictures taken at 275°C and 300°C as the melting point of tadalafil is 295°C. The experiments were repeated until 600 particles of tadalafil were analyzed.

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