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Evaluation of Piperine as Natural Coformer for Eutectics Preparation of Drugs Used in the Treatment of Cardiovascular Diseases

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Abstract

Piperine (PIP) was evaluated as a natural coformer in the preparation of multicomponent organic materials for enhancing solubility and dissolution rate of the poorly water-soluble drugs: curcumin (CUR), lovastatin (LOV), and irbesartan (IBS). A screening based on liquid assisted grinding technique was performed using 1:1 drug-PIP molar ratio mixtures, followed by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) analyses. Three eutectic mixtures (EMs) composed of CUR-PIP, LOV-PIP, and IBS-PIP were obtained. Therefore, binary phase and Tamman’s diagrams were constructed for each system to obtain the exact eutectic composition, which was 0.41:0.59, 0.29:0.71, and 0.31:0.69 for CUR-PIP, LOV-PIP, and IBS-PIP, respectively. Further, bulk materials of each system were prepared to characterize them through DSC, PXRD fully, Fourier transform infrared spectroscopy (FT-IR), and solution-state nuclear magnetic resonance (NMR) spectroscopy. In addition, the contact angle, solubility, and dissolution rate of each system were evaluated. The preserved characteristic in the PXRD patterns and FT-IR spectra of the bulk material of each system confirmed the formation of EM mixture without molecular interaction in solid-state. The formation of EM resulted in improved aqueous solubility and dissolution rate associated with the increased wettability observed by the decrease in contact angle. In addition, solution NMR analyses of CUR-PIP, LOV-PIP, and IBS-PIP suggested no significant intermolecular interactions in solution between the components of the EM. Hence, this study concludes that PIP could be an effective coformer to improve the solubility and dissolution rate of CUR, LOV, and IBS.

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Acknowledgements

Authors thank to Dr Oscar Rojas Carrillo and M. Sc. Marianelly Esquivel Alfaro for the support given in the use of the dissolution test system.

Funding

This contribution was partially funded by a grant from FEES-CONARE (Ref 115B9670). The financial support from the University of Costa Rica (UCR, Ref 115B6163), the Costa Rica Institute of Technology (TEC), the National Laboratory of Nanotechnology (LANOTEC CENAT), and the Technical University of Costa Rica (UTN).

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Authors and Affiliations

  1. Laboratorio Nacional de Nanotecnología LANOTEC-CeNAT-CONARE, 1174-1200, Pavas, San José, Costa Rica

    Krissia Wilhelm-Romero, José Roberto Vega-Baudrit & Andrea Mariela Araya-Sibaja

  2. Escuela de Química, Laboratorio BIODESS, Universidad de Costa Rica, San Pedro de Montes de Oca, 2060, San José, Costa Rica

    Krissia Wilhelm-Romero, María Isabel Quirós-Fallas, Felipe Vargas-Huertas & Mirtha Navarro-Hoyos

  3. Laboratorio de Investigación y Tecnología de Polímeros POLIUNA, Escuela de Química, Universidad Nacional de Costa Rica, Heredia, 86-3000, Costa Rica

    José Roberto Vega-Baudrit

  4. Centro de Investigación y Extensión en Materiales, Escuela de Ciencia E Ingeniería de los Materiales, Tecnológico de Costa Rica, Cartago, 159-7050, Costa Rica

    Teodolito Guillén-Girón

  5. Universidad Técnica Nacional, Alajuela, 159-7050, Costa Rica

    Andrea Mariela Araya-Sibaja

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Contributions

Conceptualization A.M.A.-S.; methodology, K.W., A.M.A.-S., F.V., M.Q. and M.N.-H.; formal analysis, K.W., F.V., M.Q.; investigation, K.W., A.M.A.-S., F.V., M.N.-H.; resources, T.G-G., J.R.V.-B., M.N.-H., A.M.A.-S.; data curation, K.W., A.M.A.-S., M.Q., F.V., M.N.-H.; writing—original draft preparation, K.W., A.M.A.-S., M.Q., F.V.; writing—review and editing, T.G-G., J.R.V.-B., M.N.-H., A.M.A.-S.; supervision, T.G-G., A.M.A.-S., J.R.V.-B., M.N.-H.; project administration, T.G-G., A.M.A.-S., M.N.-H.; funding acquisition, T.G-G., J.R.V.-B., M.N.-H. and A.M.A.S. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Andrea Mariela Araya-Sibaja.

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Wilhelm-Romero, K., Quirós-Fallas, M.I., Vega-Baudrit, J.R. et al. Evaluation of Piperine as Natural Coformer for Eutectics Preparation of Drugs Used in the Treatment of Cardiovascular Diseases. AAPS PharmSciTech 23, 127 (2022). https://doi.org/10.1208/s12249-022-02270-4

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