Desenvolvimento de novas formas sólidas multicomponentes do fármaco lornoxicam
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Data
2022-05-06
Autores
Carvalho, Ana Carina Sobral
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Universidade Estadual Paulista (Unesp)
Resumo
Devido à recorrentes problemas com a solubilidade e biodisponibilidade de insumos farmacêuticos ativos (IFAs), a modulação das propriedades físico-químicas por meio da prospecção de novas formas sólidas, tais como, sais, cocristais, eutéticos, polimorfos, entre outros, tem recebido grande destaque na comunidade científica. Isso se deve principalmente ao fato de que essas novas formas sólidas podem propiciar melhorias nas propriedades físicoquímicas sem alterar a atividade biológica do princípio ativo. Neste sentido, este trabalho objetivou o desenvolvimento de novas formas sólidas multicomponentes do fármaco lornoxicam (LOR), que é um anti-inflamatório não esteroidal, pertencente à classe dos oxicams, que apresenta problemas quando à sua baixa solubilidade aquosa. Por meio da estratégia de engenharia de cristais, foi possível obter 2 cocristais moleculares de LOR com ácido malônico (MLO) e hidroquinona (HDQ), em que foi feito um estudo sobre a influência da formação dos síntons supramoleculares nas propriedades desses cocristais. Foram também obtidos 4 novos sais de LOR, no qual 3 deles apresentam estruturas cristalinas inéditas, nunca antes reportadas. Além disso, obteve-se a formação de 10 novas formas sólidas correspondentes à síntese de cocristais iônicos. Desta maneira o estudo proposto possibilitou a compreensão das interações intermoleculares formadas nos compostos sintetizados e sua influência sobre as propriedades físico-químicas. Assim, os resultados demostram a potencialidade de se melhorar a solubilidade aquosa de fármacos por meio da modificação da estrutura sólida de materiais farmacêuticos.
Due to recurring problems with the solubility and bioavailability of active pharmaceutical ingredients (APIs), the modulation of physicochemical properties by means of prospection of new solid forms, has received great highlight in the scientific community. This is mainly due to the fact that these new solid forms can improve the physic-chemical properties without interfering in the biological activities of the active principle. In this sense, the objective of this work was the development of new solid forms of lornoxicam drug (LOR), which is a nonsteroidal anti-inflammatory (NSAD), belonging to the oxicams class, which has problems regarding its low aqueous solubility. By means of crystal engineering strategies, it was possible to obtain 2 molecular cocrystals of LOR with malonic acid (MLO) and hydroquinone (HDQ), in which was carried out a study regarding the influence of supramolecular synthons formation on the properties of these cocrystals. Was also obtained 4 salts of LOR, in which 3 of them are new and present new crystal structures, not reported before. In addition, was obtained 10 new solid forms of LOR, corresponding to the synthesis of iconic cocrystal. In this way, the proposed study allowed us to understand the intermolecular interactions formed in the synthesized compounds and their influence on the physicochemical properties. Thus, the results have demonstrated the potential to improve the aqueous solubility of drugs by modifying the solid structure of pharmaceutical materials.
Due to recurring problems with the solubility and bioavailability of active pharmaceutical ingredients (APIs), the modulation of physicochemical properties by means of prospection of new solid forms, has received great highlight in the scientific community. This is mainly due to the fact that these new solid forms can improve the physic-chemical properties without interfering in the biological activities of the active principle. In this sense, the objective of this work was the development of new solid forms of lornoxicam drug (LOR), which is a nonsteroidal anti-inflammatory (NSAD), belonging to the oxicams class, which has problems regarding its low aqueous solubility. By means of crystal engineering strategies, it was possible to obtain 2 molecular cocrystals of LOR with malonic acid (MLO) and hydroquinone (HDQ), in which was carried out a study regarding the influence of supramolecular synthons formation on the properties of these cocrystals. Was also obtained 4 salts of LOR, in which 3 of them are new and present new crystal structures, not reported before. In addition, was obtained 10 new solid forms of LOR, corresponding to the synthesis of iconic cocrystal. In this way, the proposed study allowed us to understand the intermolecular interactions formed in the synthesized compounds and their influence on the physicochemical properties. Thus, the results have demonstrated the potential to improve the aqueous solubility of drugs by modifying the solid structure of pharmaceutical materials.
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Palavras-chave
Agentes anti-inflamatórios, Cristalização, Solubilidade, Análise térmica, Medicamentos - Formas farmacêuticas