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Development, Quality by Design-Based Optimization, and Stability Assessment of Oral Liquid Formulations Containing Baclofen for Hospital Use

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Abstract

The absence of oral liquid pharmaceutical forms appropriate for use in pediatric and adult patients with difficulty swallowing is a public health problem, especially in the hospital context. Baclofen is a muscle relaxant of choice for treating spasticity, generally marketed only in tablet form, highlighting the need for liquid formulations to facilitate dose adjustment, administration, and swallowing. The present study aimed to develop oral liquid formulations containing baclofen, optimize them through the quality by design approach, and evaluate their physicochemical and microbiological stability. Preformulation and preliminary stability studies were carried out for the development of formulations. Experimental screening and optimization designs resulted in eleven experiments for each step that were evaluated for 28 days. A stability-indicating method by high-performance liquid chromatography presented linearity, low limits of detection and quantification, precision, accuracy, and robustness. The experimental design led to two optimized formulations containing baclofen, glycerin, potassium sorbate, citric acid, ultrapure water, flavor, and sucrose syrup or sodium carboxymethylcellulose solution as a vehicle, the last one with sucralose as a sweetener. The formulations were placed in amber glass flasks and subjected to a physicochemical and microbiological stability study. Both formulations showed physicochemical and microbiological stability when stored at room temperature and refrigerated for 84 days. The results of this study may serve as a reference in the preparation of liquid oral formulations containing baclofen in the hospital routine and collaborate with the safety and adherence to the treatment of adult and pediatric patients.

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Funding

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brazil (CAPES)—Finance Code 001.

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Authors and Affiliations

  1. Pharmaceutical Sciences Graduate Program, Federal University of Rio Grande Do Sul (UFRGS), 2752 Ipiranga Ave, Porto Alegre, RS, Brazil

    Elisa de Saldanha Simon, Caren Gobetti, Nadia Maria Volpato & Martin Steppe

  2. College of Pharmacy, Federal University of Rio Grande Do Sul (UFRGS), 2752 Ipiranga Ave., Laboratory 402, Santana, Porto Alegre, RS, 90610-000, Brazil

    Elisa de Saldanha Simon & Gabriele Bordignon Primieri

  3. College of Pharmacy, Federal University of Bahia (UFBA), 147 Barão Do Jeremoabo St, Salvador, BA, Brazil

    Nathalie Ribeiro Wingert

  4. Semi Industrial Pharmacy, Hospital de Clínicas de Porto Alegre (HCPA), 2350 Ramiro Barcelos St, Porto Alegre, RS, Brazil

    Márcio Vinícius Ayres & Silvia Helena Oliveira de Almeida

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  1. Elisa de Saldanha Simon
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Contributions

ESS: conceptualization, study design, research, experimental work, data collection, interpretation of data, analysis methodology, investigation, writing (original draft).

NRW: analysis and interpretation of data, writing review.

CG: experimental work, data collection, analysis methodology.

GBP: experimental work, data collection.

MVA and SHOA: consultation, collaboration.

NMV: conceptualization, methodology, consultation, collaboration.

MS: conceptualization, methodology, project administration, supervision, writing review.

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Correspondence to Elisa de Saldanha Simon.

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de Saldanha Simon, E., Wingert, N.R., Gobetti, C. et al. Development, Quality by Design-Based Optimization, and Stability Assessment of Oral Liquid Formulations Containing Baclofen for Hospital Use. AAPS PharmSciTech 23, 301 (2022). https://doi.org/10.1208/s12249-022-02447-x

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