ESTIMATION OF IN VITRO AND IN VIVO PERFORMANCE OF METRONIDAZOLE ORAL DOSAGE FORMS

JOSE RAUL MEDINA-LOPEZ; YONATAN JOCEL GOMEZ-VARGAS; HEDWYN RODOLFO MENDEZ-HERNANDEZ; FELIPE DINO REYES-RAMIREZ; JUAN CARLOS RUIZ-SEGURA; MARCELA HURTADO

doi:10.22159/ijap.2023v15i4.48137

Authors

JOSE RAUL MEDINA-LOPEZ Departamento Sistemas Biológicos, Universidad Autónoma Metropolitana-Xochimilco, Mexico City, Mexico https://orcid.org/0000-0002-4159-8403
YONATAN JOCEL GOMEZ-VARGAS Departamento Sistemas Biológicos, Universidad Autónoma Metropolitana-Xochimilco, Mexico City, Mexico https://orcid.org/0009-0006-6565-4437
HEDWYN RODOLFO MENDEZ-HERNANDEZ Departamento Sistemas Biológicos, Universidad Autónoma Metropolitana-Xochimilco, Mexico City, Mexico
FELIPE DINO REYES-RAMIREZ Departamento Sistemas Biológicos, Universidad Autónoma Metropolitana-Xochimilco, Mexico City, Mexico https://orcid.org/0009-0009-6876-9223
JUAN CARLOS RUIZ-SEGURA Departamento Sistemas Biológicos, Universidad Autónoma Metropolitana-Xochimilco, Mexico City, Mexico https://orcid.org/0000-0003-2304-7971
MARCELA HURTADO Departamento Sistemas Biológicos, Universidad Autónoma Metropolitana-Xochimilco, Mexico City, Mexico https://orcid.org/0000-0003-3546-5986

DOI:

https://doi.org/10.22159/ijap.2023v15i4.48137

Keywords:

Convolution, Inverse release function, Metronidazole, Prediction error, Tablets

Abstract

Objective: To estimate plasma concentrations-time profiles of metronidazole commercial tablets through in vitro dissolution data using the Inverse Release Function approach and a convolution method.

Methods: Dissolution profiles of metronidazole reference tablets (500 mg) were obtained using USP Apparatus 1 at 100 rpm, USP Apparatus 4 at 16 ml/min, and 0.1 N HCl, pH 4.5 acetate buffer and pH 6.8 phosphate buffer as dissolution media. Additionally, three generic drug products were tested using USP Apparatus 1 and pH 4.5 acetate buffer. Drug was quantified at 278 nm until 60 min. Dissolution parameters such as mean dissolution time, area under the cumulative dissolution curve, and dissolution efficiency were calculated. Metronidazole plasma levels were predicted considering the in vitro release data and published information. Percent of prediction error (PE) for C_max and AUC_0-inf at each condition was calculated.

Results: When comparing dissolution profiles with common dissolution parameters (USP 1 vs. 4) significant differences were found (*P<0.05). Values of PE for C_max and AUC_0-inf were within range (±15%) only with USP Apparatus 1 and pH 4.5 acetate buffer. Using these conditions when comparing generic drug products vs. reference formulation, significant differences were found (*P<0.05) and values of PE for AUC_0-inf were out of the range.

Conclusion: The obtained information suggests using USP Apparatus 1 and pH 4.5 acetate buffer to predict the in vivo performance of metronidazole tablets. The impact of in vitro differences of all generic formulations was confirmed with differences in predicted in vivo performance.

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