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Development of Losartan Orally Disintegrating Tablets by Direct Compression: a Cost-Effective Approach to Improve Paediatric Patient’s Compliance

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Abstract

The development of suitable dosage forms is essential for an effective pharmacological treatment in children. Orally disintegrating tablets (ODTs) are attractive dosage forms that avoid swallowing problems, ensure dosage accuracy and are easy to administer as they disintegrate in the oral cavity. This study aimed to develop ODTs containing losartan potassium (LP) for the treatment of arterial hypertension in children. The ODTs, produced by the cost-effective manufacturing process of direct compression, consisted of a mixture of diluent, superdisintegrant, glidant and lubricant. Five superdisintegrants (croscarmellose sodium, two grades of crospovidone, sodium starch glycolate and pregelatinized starch) were tested (at two concentrations), and combined with three diluents (mannitol, lactose and sorbitol). Thus, thirty formulations were evaluated based on disintegration time, hardness and friability. Two formulations, exhibiting the best results concerning disintegration time (< 30 s), hardness and friability (≤ 1.0%), were selected as the most promising ones for further evaluation. These ODTs presented favourable drug-excipient compatibility, tabletability and flow properties. The in vitro dissolution studies demonstrated ‘very rapid’ drug release. Preliminary stability studies highlighted the requirement of a protective packaging. All quality properties retained appropriate results after 12 months of storage in airtight containers. In conclusion, the ODTs were successfully developed and characterised, suggesting a potential means to accomplish a final prototype that enables an improvement in childhood arterial hypertension treatment.

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Acknowledgements

The authors wish to thank Chutrau (Argentina) and DFE Pharma (Germany) for the kind donation of lactose SuperTab®50 ODT and Rumapel (Argentina) for donation of crospovidone (Kollidon® CL and CL-SF). Furthermore, the authors wish to acknowledge Luciano Benedini for his technical assistance. Candela Juan is grateful to Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) and Agencia Nacional de Laboratorios Públicos (ANLAP) for the PhD fellowship.

Funding

This work was supported by Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) (grant number PIBAA 28720210100113CO), ANLAP (grant number EX-2020–50428127-APN-ANLAP#MS), Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT) (grant number PICT-2021-GRT-TI-00524) and Universidad Nacional del Sur (UNS) (grant number PGI 24/B306).

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Authors and Affiliations

  1. Departamento de Biología, Bioquímica y Farmacia-Universidad Nacional del Sur (UNS), Bahía Blanca, Buenos Aires, Argentina

    Candela Juan, Loreana Gallo & Noelia Gonzalez Vidal

  2. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Bahía Blanca, Buenos Aires, Argentina

    Candela Juan & Noelia Gonzalez Vidal

  3. Planta Piloto de Ingeniería Química (PLAPIQUI, UNS-CONICET), Bahía Blanca, Buenos Aires, Argentina

    Loreana Gallo

Authors
  1. Candela Juan
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  2. Loreana Gallo
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  3. Noelia Gonzalez Vidal
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Contributions

All authors contributed to the design of the study, interpretation of outcomes, writing, editing and revision of the manuscript. In detail, CJ executed the experiments and wrote the original draft; both LG and NGV were responsible for the project design and administration and the acquisition and management of funding resources.

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Correspondence to Noelia Gonzalez Vidal.

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Juan, C., Gallo, L. & Gonzalez Vidal, N. Development of Losartan Orally Disintegrating Tablets by Direct Compression: a Cost-Effective Approach to Improve Paediatric Patient’s Compliance. AAPS PharmSciTech 25, 79 (2024). https://doi.org/10.1208/s12249-024-02796-9

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