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The Impact of Solid Dispersion on Formulation, Using Confocal Micro Raman Spectroscopy as Tool to Probe Distribution of Components

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Abstract

Purpose

Solid dispersions (SDs) of a poorly water-soluble drug were prepared, and their physicochemical properties were compared to those of control physical mixtures (PMs). Among the multiple techniques used to characterize the solid state of preparations, confocal micro Raman spectroscopy (CMRS) was used as a non-destructive tool to qualitatively probe content uniformity and distribution of drug and carrier.

Methods

SDs and PMs of drug (fenbendazole, FBZ) were prepared containing two different carriers (poloxamer P188 or P407) with different drug polymer ratios. The preparations were characterized by powder X-ray diffractometry, Fourier transform infrared spectroscopy, thermal analysis, scanning electron microscopy, and in vitro dissolution assay. In addition, CMRS technique and principal component analysis (PCA) were used in order to statistically define the content uniformity and distribution of the drug within the polymeric matrix.

Results

In vitro dissolution results exhibited a marked improvement when the drug was formulated as SD compared to control PM and to pure drug. The solid state of these preparations characterized by X-ray powder diffraction and Fourier transform infrared spectroscopy showed no changes in the crystalline state of the drug and no chemical interactions between the components. Raman studies showed a better content uniformity of the drug within the polymeric matrix when subjected to SD process, correlating with the improved dissolution profile.

Conclusion

This study provides evidence of the potential of the confocal Raman imaging technique, providing a fast and powerful method to characterize solid dispersions which could be incorporated towards the use of quality by design (QbD) approaches in pharmaceutical development.

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Acknowledgments

The authors especially thank Dario O. Weitmann, Business Coordinator BCS in BASF Argentina S.A for the Poloxamer samples, Q.F. Antonio Malanga (BIOTEFA—Instituto Polo Tecnológico de Pando, Facultad de Química, UdelaR, Uruguay) for kindly providing access to the necessary equipment, and Lourdes Martino, who edited this paper. The authors acknowledge Prof. Dr. Alejandro Ayala (Universidade Federal do Ceará, UFC, Brazil) for providing DSC and TG measurement, and Fernando Pignanelli (Facultad de Química, UdelaR, Uruguay) for the help in the implementation of PCA and the peak-to-peak computational scripts for the data analysis.

Funding

This work was supported by grants from the Programa de Desarrollo de Ciencias Básicas (PEDECIBA, Uruguay), ANII (Agencia Nacional de Investigación e Innovación, Uruguay), Project ANII-EQC-X-2012-1-14 IPTP, AUGM (Asociación de Universidades del Grupo Montevideo), SECyT-UNC, CONICET, ANPCyT (Argentina).

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Authors and Affiliations

  1. Área de Farmacología, Depto. CIENFAR, Facultad de Química, Universidad de la República (Udelar), Av. General Flores 2124, Montevideo, Uruguay

    M. Elisa Melian, A. Beatriz Munguía & Laura Domínguez

  2. Centro NanoMat & Cryssmat-Lab, DETEMA, Facultad de Química, Universidad de la República (Udelar), Av. General Flores 2124, Montevideo, Uruguay

    Ricardo Faccio

  3. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica, UNITEFA (UNC-CONICET), Depto. de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba (UNC), Haya de la Torre y Medina Allende, Ciudad Universitaria, Córdoba, Argentina

    Santiago Palma

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  1. M. Elisa Melian
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  2. A. Beatriz Munguía
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  3. Ricardo Faccio
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  4. Santiago Palma
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  5. Laura Domínguez
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Correspondence to Laura Domínguez.

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Melian, M.E., Munguía, A.B., Faccio, R. et al. The Impact of Solid Dispersion on Formulation, Using Confocal Micro Raman Spectroscopy as Tool to Probe Distribution of Components. J Pharm Innov 13, 58–68 (2018). https://doi.org/10.1007/s12247-017-9306-9

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