Dispersões sólidas amorfas como estratégia tecnológica para aprimorar a biodisponibilidade de fármacos
DOI:
https://doi.org/10.34117/bjdv11n9-053Keywords:
dispersões sólidas amorfas, solubilidade, taxa de dissolução, biodisponibilidadeAbstract
Os fármacos podem ser encontrados nos estados cristalino, co-cristalino ou amorfo, sendo que o estado cristalino geralmente apresenta menor solubilidade em água e, consequentemente, reduzida biodisponibilidade. A manipulação do estado sólido representa uma estratégia promissora para melhorar a taxa de dissolução e a biodisponibilidade de fármacos classificados nos grupos II e IV do Sistema de Classificação Biofarmacêutica (SCB). Nesse contexto, as dispersões sólidas amorfas (DSA) destacam-se como uma tecnologia eficaz, ao promover a conversão do fármaco do estado cristalino para o amorfo, com o auxílio de um agente dispersante. O presente estudo trata-se de uma revisão narrativa da literatura, elaborada a partir de uma estratégia de busca estruturada em bases de dados científicas. Os artigos selecionados abordam aspectos fundamentais como solubilidade, dissolução, modificação do estado sólido e seu impacto na biodisponibilidade oral. Adicionalmente, a revisão explora ainda as definições e classificações das DSA, os métodos empregados na sua obtenção, técnicas de caracterização e os desafios relacionados à estabilidade físico-química desses sistemas farmacêuticos ao longo do tempo.
References
ABOUD, Z. et al. Enhancing drug release from amorphous solid dispersions: Overcoming limitations of binary systems. Pharmaceutics, v. 12, n. 7, p. 658, 2020. DOI: https://doi.org/10.3390/pharmaceutics12070658. Acesso em: 7 jul. 2025.
ALVES, T. F., et al. Association of Silver Nanoparticles and Curcumin Solid Dispersion: Antimicrobial and Antioxidant Properties. AAPS PharmSciTech 19, 225–231. 2018a. https://doi.org/10.1208/s12249-017-0832-z. Disponível em: https://link.springer.com/article/10.1208/s12249-017-0832-z#citeas. Acesso em: 26 jun. 2025.
BAGHEL, S.; CATHCART, H.; O’REILLY, N. J. Polymeric Amorphous Solid Dispersions: A Review of Amorphization, Crystallization, Stabilization, Solid-State Characterization, and Aqueous Solubilization of Biopharmaceutical Classification System Class II Drugs. Journal of Pharmaceutical Sciences, v. 105, n. 9, p. 2527-44, set. 2016. Disponível em: https://jpharmsci.org/article/S0022-3549(15)00009-X/fulltext. Acesso em 12 jun. 2025.
BHALANI, P. et al. Bioavailability enhancement techniques for poorly aqueous soluble drugs and therapeutics. Biomedicines, v. 10, n. 9, p. 2055, 2022. DOI: 10.3390/biomedicines10092055. Disponível em: https://www.mdpi.com/2227-9059/10/9/2055. Acesso em: 7 jul. 2025.
BIN TIAN, W.; GAO, W.; TAO, X.; TANG, X.; TAYLOR, L. S. Impact of Polymers on the Melt Crystal Growth Rate of Indomethacin Polymorphs. Crystal Growth & Design, v. 17, n. 12, p. 6467-6476, 2017. DOI: 10.1021/acs.cgd.7b01145. Disponível em: https://doi.org/10.1021/acs.cgd.7b01145. Acesso em: 7 jul. 2025.
BHANDARI, G. et al. Effect of moisture-induced phase separation on the physical stability of amorphous solid dispersions. Molecular Pharmaceutics, v. 18, n. 3, p. 1107–1118, 2021. DOI: https://doi.org/10.1021/acs.molpharmaceut.0c01062. Acesso em: 7 jul. 2025.
BHUJBAL, S. V. et al. Pharmaceutical amorphous solid dispersion: A review of manufacturing strategies. Acta Pharmaceutica Sinica B, v. 11, n. 8, p. 2533–2564, 2021. DOI: https://doi.org/10.1016/j.apsb.2021.03.034. Acesso em: 7 jul. 2025.
CHAUD, M. V., TAMASCIA, P., LIMA, A. C., PAGANELLI, M. O., GREMIÃO, M. P. D., FREITAS, O. Solid dispersions with hydrogenated castor oil increase solubility, dissolution rate and intestinal absorption of praziquantel. Brazilian Journal of Pharmaceutical Sciences, 46(3), 473–481. 2010. Disponível em: https://doi.org/10.1590/S1984-82502010000300010. Acesso em: 15 jun. 2025.
HAN, J. et al. Amorphous solid dispersions: Stability mechanism, design strategy and key production technique of hot melt extrusion. International Journal of Pharmaceutics, v. 646, p. 123490, 2023. DOI: 10.1016/j.ijpharm.2023.123490. Disponível em: https://pubmed.ncbi.nlm.nih.gov/37805146/. Acesso em: 7 jul. 2025.
JARA, M. O. et al. Comparative study of Hot-Melt Extrusion, spray drying, and KinetiSol® processing to formulate a poorly water-soluble and thermolabile drug. International Journal of Pharmaceutics, v. 676, p. 125582, 15 maio 2025. Disponível em: https://doi.org/10.1016/j.ijpharm.2025.125582. Acesso em: 27 jul. 2025.
KANEKO, Y. et al. Miscibility and phase separation in binary amorphous solid dispersions: Recent advances. International Journal of Pharmaceutics, v. 631, p. 122442, 2023. DOI: https://doi.org/10.1016/j.ijpharm.2023.122442.
KAUSHIK, R.; BUDHWAR, V.; KAUSHIK, D. An Overview on Recent Patents and Technologies on Solid Dispersion. Recent Patents on Drug Delivery & Formulation, v. 14, n. 1, p. 63-74, 2020. DOI: 10.2174/1872211314666200117094406. Disponível em: https://doi.org/10.2174/1872211314666200117094406. Acesso em: 7 jul. 2025.
KIM, D. et al. Impact of polymer selection on the physical stability of amorphous solid dispersions: Recent insights. Journal of Pharmaceutical Sciences, v. 112, n. 1, p. 35–48, 2023. DOI: https://doi.org/10.1016/j.xphs.2022.08.007.
KUMAR, S. et al. Advances in the development of amorphous solid dispersions. Journal of Pharmaceutical Sciences, v. 110, n. 3, p. 1230-1242, 2021. DOI: 10.1016/j.xphs.2020.11.012. Disponível em: https://www.sciencedirect.com/science/article/pii/S1818087623000612. Acesso em: 7 jul. 2025.
KRAWCZYK M. S, SROKA A, MAJERZ I. The Crystal Structure and Intermolecular Interactions in Fenamic Acids-Acridine Complexes. Molecules. 2021 May 16;26(10):2956. doi: 10.3390/molecules26102956. PMID: 34065674; PMCID: PMC8156396.
LI, J. et al. Preparation of Azithromycin Amorphous Solid Dispersion by Hot-Melt Extrusion: An Advantageous Technology with Taste Masking and Solubilization Effects. Polymers (Basel). 2022. doi: 10.3390/polym14030495. PMID: 35160485; PMCID: PMC8840525. Disponível em: https://pubmed.ncbi.nlm.nih.gov/35160485/. Acesso em 20 ago. 2024.
LUNA ROCHA, T. C. et al. Development and evaluation of the in vitro schistosomicidal activity of solid dispersions based on 2-(-5-bromo-1-H-indole-3-yl-methylene)-N-(naphthalene-1-ylhydrazine-carbothiamide. Experimental Parasitology, v. 256, p. 108626, jan. 2024. Disponível em: https://doi.org/10.1016/j.exppara.2023.108626. Acesso em: 27 jul. 2025.
MUJTABA, M. A. et al. Development of Hot Melt Extruded Co-Formulated Artesunate and Amodiaquine-Soluplus® Solid Dispersion System in Fixed-Dose Form: Amorphous State Characterization and Pharmacokinetic Evaluation. Current Drug Metabolism, v. 25, n. 7, p. 505–522, 2024. DOI: 10.2174/0113892002330772240912055518. Acesso em: 27 jul. 2025.
MOSESON D. E., TRAN, T. B., KARUNAKARAN B., AMBARDEKAR, R., HIEW., T. N. Trends in amorphous solid dispersion drug products approved by the U.S. Food and Drug Administration between 2012 and 2023. Int J Pharm X. 2024 Jun; 7: 100259. Disponível em https://pubmed.ncbi.nlm.nih.gov/38974024/. Acesso em 17 ago. 2024.
PATEL, R. et al. Trends in amorphous solid dispersion drug products approved by the U.S. Food and Drug Administration between 2012 and 2023. Pharmaceutical Research, v. 42, n. 2, p. 45-56, 2025. DOI: 10.1007/s11095-024-03598-7. Disponível em: https://www.researchgate.net/publication/381135103_Trends_in_amorphous_solid_dispersion_drug_products_approved_by_the_US_Food_and_Drug_Administration_between_2012_and_2023. Acesso em: 7 jul. 2025.
PAWAR, J. et al. Drug loading limits in amorphous solid dispersions: Recent understanding and future prospects. Molecular Pharmaceutics, v. 18, n. 9, p. 3366–3380, 2021. DOI: https://doi.org/10.1021/acs.molpharmaceut.1c00430.
QIANG, W. et al. Microwave-induced in situ amorphization: A new strategy for tackling the stability issue of amorphous solid dispersions. Pharmaceutics, v. 12, n. 7, p. 655, 2020. DOI: 10.3390/pharmaceutics12070655. Disponível em: https://doi.org/10.3390/pharmaceutics12070655. Acesso em: 7 jul. 2025.
RAY, L.; ILIFF, J. J.; HEYS, J. J. Analysis of convective and diffusive transport in the brain interstitium. Fluids and Barriers of the CNS, v. 16, n. 6, 2019. DOI: 10.1186/s12987-019-0126-9. Disponível em: https://doi.org/10.1186/s12987-019-0126-9. Acesso em: 7 jul. 2025.
ROCHA, B.; DE MORAIS, L. A.; VIANA, M. C.; CARNEIRO, G. Promising strategies for improving oral bioavailability of poor water-soluble drugs. Expert Opinion on Drug Discovery, v. 18, n. 6, p. 615–627, 2023. DOI: 10.1080/17460441.2023.2211801. Disponível em: https://doi.org/10.1080/17460441.2023.2211801. Acesso em: 7 jul. 2025.
SABERI, S. et al. Influence of plasticizers on the properties of amorphous solid dispersions prepared by hot melt extrusion. Journal of Drug Delivery Science and Technology, v. 75, p. 103649, 2023. DOI: 10.1016/j.jddst.2023.103649. Disponível em: https://doi.org/10.1016/j.jddst.2023.103649. Acesso em: 7 jul. 2025.
SAI, K. et al. Design and characterization of microwave irradiation assisted amorphous solid dispersion of resveratrol. Indian Journal of Pharmaceutical Education and Research, v. 59, n. 2, p. 574-581, 2025. DOI: 10.5530/ijper.59.2.94. Disponível em: https://ijper.org/sites/default/files/IndJPhaEdRes-59-2-574.pdf. Acesso em: 7 jul. 2025.
SINGH, D. et al. Current trends on solid dispersions: Past, present, and future. Pharmaceutical Research, v. 38, n. 1, p. 1-10, 2022. DOI: 10.1007/s11095-021-03113-1. Disponível em: https://pmc.ncbi.nlm.nih.gov/articles/PMC9617737/. Acesso em: 7 jul. 2025.
SINGH, G. et al. Ternary amorphous solid dispersions: A review of design, performance, and future perspectives. International Journal of Pharmaceutics, v. 634, p. 122670, 2023. DOI: https://doi.org/10.1016/j.ijpharm.2023.122670.
SU, D. et al. Combining solubilization and controlled release strategies to prepare pH-sensitive solid dispersion loaded with albendazole: In vitro and in vivo studies. Frontiers in Veterinary Science, v. 11, p. 1522856, 2024. DOI: 10.3389/fvets.2024.1522856. Disponível em: https://doi.org/10.3389/fvets.2024.1522856. Acesso em: 7 jul. 2025.
SHI, Q. et al. Amorphous Solid Dispersions: Role of the Polymer and Its Importance in Physical Stability and In Vitro Performance. Pharmaceutics, v. 14, n. 8, p. 1747, 2022. DOI: https://doi.org/10.3390/pharmaceutics14081747.
STIELOW, M.; WITCZYŃSKA, A.; KUBRYŃ, N.; FIJAŁKOWSKI, Ł.; NOWACZYK, J.; NOWACZYK, A. The Bioavailability of Drugs—The Current State of Knowledge. Molecules, v. 28, n. 24, p. 8038, 2023. DOI: 10.3390/molecules28248038. Disponível em: https://doi.org/10.3390/molecules28248038. Acesso em: 7 jul. 2025.
WANG, J. et al. Cryogenic milling techniques for amorphous solid dispersions: Mechanisms and stability. Drug Development and Industrial Pharmacy, v. 47, n. 3, p. 365-374, 2021. DOI: 10.1080/03639045.2020.1810860. Disponível em: https://www.sciencedirect.com/science/article/pii/S0928098721001603. Acesso em: 7 jul. 2025.
WANG, X. et al. Recent advances in ternary amorphous solid dispersions: Strategies for enhanced stability and performance. Pharmaceutics, v. 15, n. 3, p. 758, 2023. DOI: https://doi.org/10.3390/pharmaceutics15030758.
ZHAO, Y. et al. Amorphous solid dispersions: An update for preparation and characterization. International Journal of Pharmaceutics, v. 610, p. 121245, 2021. DOI: 10.1016/j.ijpharm.2021.121245. Disponível em: https://www.sciencedirect.com/science/article/abs/pii/S0378517320305445. Acesso em: 7 jul. 2025.
ZHOU, F. et al. Amorphous solid dispersions: Stability mechanism, design strategy and key production technique of hot melt extrusion. International Journal of Pharmaceutics, v. 646, p. 123490, 2022. DOI: 10.1016/j.ijpharm.2022.123490. Disponível em: https://www.sciencedirect.com/science/article/abs/pii/S0378517323009110. Acesso em: 7 jul. 2025.
