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Production of Isotonic, Sterile, and Kinetically Stable Lipid-Core Nanocapsules for Injectable Administration

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Abstract

Lipid-core nanocapsules (LNC) were designed and prepared as a colloidal system for drug targeting to improve the stability of drugs and allow their controlled release. For parenteral administration, it is necessary to ensure formulation sterility. However, sterilization of nanotechnological devices using an appropriate technique that keeps the supramolecular structure intact remains a challenge. This work aimed to evaluate the effect of autoclaving on the physicochemical characteristics of LNC. Formulations were prepared by the self-assembling method, followed by isotonization and sterilization at varying times and temperatures. The isotonicity was confirmed by determining the freezing temperature, which was −0.51°C. The formulation was broadly characterized, and the diameter of the particles was determined utilizing complementary methods. To evaluate the chemical stability of poly(ε-caprolactone), its molecular weight was determined by size exclusion chromatography. The physicochemical characteristics (average diameter, viscosity, and physical stability) of the formulation were similar before and after adding glycerol and conducting the sterilization at the highest temperature (134°C) and the shorter exposure time (10 min). After autoclaving, the sterility test was performed and showed no detectable microbial growth. Multiple light scattering demonstrated that the formulations were kinetically stable, and the mean diameter was constant for 6 months, corroborating this result. The polymer was chemically stable in the sterilized formulation. Isotonic and sterile LNC aqueous suspensions were produced using glycerol and autoclaving. Briefly, the results open an opportunity to produce an isotonic and sterile LNC aqueous dispersion applicable as nanomedicine for intravenous administration in clinical trials.

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Acknowledgments

This study was supported by the Brazilian agencies: CNPq/Brazil, CAPES, and FAPERGS. Karina Paese thanks CNPq/Brazil for your fellowships. Still, the authors thank Dr. Neila Silvia Pereira dos Santos Richards (Universidade Federal de Santa Maria) by the Digital Electronic Cryoscope MK 540L analysis and Dr. Andrea Troller Pinto (Universidade Federal do Rio Grande do Sul) by Digital Electronic Cryoscope PZL 7000, PZL, Brazil.

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Authors and Affiliations

  1. Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga, 2752/Lab. 405, Porto Alegre, 90610-000, RS, Brazil

    Karina Paese, Manoel Ortiz, Luiza Abrahão Frank, Irene C. Külkamp-Guerreiro, Adriana R. Pohlmann & Silvia S. Guterres

  2. Departamento de Farmácia Industrial, Universidade Federal de Santa Maria, Santa Maria, 97105-900, Brazil

    Clarice M. B. Rolim

  3. Programa de Pós-Graduação em Ciências Fisiológicas – Fisiologia Animal Comparada, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande, Rio Grande, 96210-900, RS, Brazil

    Daniela M. Barros

  4. Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Bento Gonçalves 9500, Porto Alegre, 91501-970, Brazil

    Adriana R. Pohlmann

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  1. Karina Paese
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  2. Manoel Ortiz
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  3. Luiza Abrahão Frank
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Correspondence to Karina Paese.

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Paese, K., Ortiz, M., Frank, L.A. et al. Production of Isotonic, Sterile, and Kinetically Stable Lipid-Core Nanocapsules for Injectable Administration. AAPS PharmSciTech 18, 212–223 (2017). https://doi.org/10.1208/s12249-016-0493-3

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