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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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Related in: MedlinePlus

Change of d(0.1), d(0.5), and d(0.9) of meloxicam PSDs over volume of water used. Reference values belong to raw meloxicam.
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fig4: Change of d(0.1), d(0.5), and d(0.9) of meloxicam PSDs over volume of water used. Reference values belong to raw meloxicam.

Mentions: Because it was found that granulation binders, used in the granulation process, caused hardening of prepared powder, directly compressed tablets ME Tbl 1 were used for these experiments. Figure 4 shows change of d-values of meloxicam PSDs over volume of water used for the disintegration. PSD analyses were carried out using the method described in mechanical disintegration. Almost no change of d-values was observed if 0.5 mL of water was used. This volume equals the volume being required to dissolve all sufficiently soluble components of ME Tbl 1 tablet [20]. It can be calculated as a saturated solution of all sufficiently soluble components in a tablet [21]. In our case, more than 0.5 mL of water caused partial dissolution of meloxicam particles.


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 meloxicam PSDs over volume of water used. Reference values belong to raw meloxicam.
© Copyright Policy
Related In: Results  -  Collection

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

fig4: Change of d(0.1), d(0.5), and d(0.9) of meloxicam PSDs over volume of water used. Reference values belong to raw meloxicam.
Mentions: Because it was found that granulation binders, used in the granulation process, caused hardening of prepared powder, directly compressed tablets ME Tbl 1 were used for these experiments. Figure 4 shows change of d-values of meloxicam PSDs over volume of water used for the disintegration. PSD analyses were carried out using the method described in mechanical disintegration. Almost no change of d-values was observed if 0.5 mL of water was used. This volume equals the volume being required to dissolve all sufficiently soluble components of ME Tbl 1 tablet [20]. It can be calculated as a saturated solution of all sufficiently soluble components in a tablet [21]. In our case, more than 0.5 mL of water caused partial dissolution of meloxicam particles.

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