Article
Multidisciplinary Sciences
Juliana M. C. Barbosa, Caroline D. Nicoletti, Patricia B. da Silva, Tatiana G. Melo, Debora O. Futuro, Vitor F. Ferreira, Kelly Salomao
Summary: The treatment of Chagas disease is currently limited to two drugs with severe side effects, hence the need for alternative drugs. This study aims to investigate the in vitro anti-T. cruzi effects of encapsulated beta-Lap and its potential toxicity using 2HP-beta-CD as a drug delivery system.
Article
Pharmacology & Pharmacy
Jiayi Qian, Fei Li, Chunxue Zhang, Shuo Chai, Tingting Liu, Xiaoyu Sui
Summary: This study investigated the effects of PEG 4000, PVP K30, poloxamer 407, and urea as carriers for glycyrrhetinic acid solid dispersions (GA-SDs) on dissolution behavior and physicochemical properties. The results showed that GA-SDs prepared with four different carriers had better dissolution properties compared to the pure drug and physical mixtures. Among the carriers, PVP K30 showed the greatest enhancement effect on dissolution rate and equilibrium solubility.
PAKISTAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Josue Pozo-Martinez, Francisco Salgado, Ana Liempi, Ulrike Kemmerling, Raul Mera-Adasme, Claudio Olea-Azar, Mauricio Moncada-Basualto, Fernanda Borges, Eugenio Uriarte, Maria Joao Matos
Summary: The study demonstrated that a series of catechol-containing 3-arylcoumarins have moderate trypanocidal activity on the trypomastigote form of the parasite, with 3-(4'-bromophenyl)-6,7-dihydroxycoumarin (8) showing the highest activity but also the highest cytotoxicity in Vero cells. The inclusion in beta-cyclodextrins reduced the trypanocidal activity and cytotoxicity, but increased solubility. Compound 8 was found to act through the generation of oxidative stress, and the combination with BZN showed a synergistic effect, reducing the necessary dose of BZN and proving to be a promising alternative strategy for treating the disease.
ARABIAN JOURNAL OF CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Clara E. Correa-Soto, Yi Gao, Anura S. Indulkar, Geoff G. Z. Zhang, Lynne S. Taylor
Summary: Amorphous solid dispersion formulations (ASD) are used to improve the bioavailability of poorly soluble drugs. This study investigated the addition of surfactants to atazanavir-copovidone ASDs to increase the limit of congruency (LoC). The results showed that addition of certain surfactants increased the LoC and enhanced drug release from the ASDs.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Pharmacology & Pharmacy
Isaie Nyamba, Olivier Jennotte, Charles B. Sombie, Anna Lechanteur, Pierre-Yves Sacre, Abdoulaye Djande, Rasmane Semde, Brigitte Evrard
Summary: To exploit the therapeutic potential of ellagic acid, strategies to enhance its solubility, dissolution rate, and bioavailability are necessary. Among the pre-selected polymers, Eudragit® EPO showed the most promising results for solid dispersions of ellagic acid, with a stable supersaturated solution and significantly higher solubility. The extrudates based on this polymer also showed a high dissolution rate, and increasing the loading rate did not negatively affect drug release.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Pharmacology & Pharmacy
Yang Kong, Wenhan Wang, Changzhao Wang, Lintao Li, Donglei Peng, Bin Tian
Summary: Amorphous solid dispersion (ASD) is a potential approach for improving the solubility and bioavailability of poorly water-soluble drugs by generating supersaturated drug solutions. The dissolution behavior of ASD has attracted increasing attention. This review highlights recent advancements in ASD dissolution, including the generation and maintenance of supersaturated drug solutions and the mechanisms of drug release. It also discusses the formation of drug-rich nanodroplets during dissolution and their underlying mechanisms, as well as the impact of phase separation morphology on the dissolution behavior of hydrated ASD. The review also explores the effects of polymers and surfactants on the physical stability of supersaturated drug solutions.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Pharmacology & Pharmacy
Daiki Hirai, Hiroki Tsunematsu, Shin-ichiro Kimura, Shigeru Itai, Toshiro Fukami, Yasunori Iwao
Summary: Amorphous solid dispersion (ASD) is a widely used preparation for enhancing the solubility and oral absorption of poorly water-soluble drugs. The study presents a new mathematical model to analyze the dissolution characteristics of ASDs and investigate the relationship between model parameters and dissolution behavior. The results provide insights into the factors influencing the dissolution behavior of different combinations of drug-polymer ASDs.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Alina E. Perrone, Mariana Pinillo, Marcela S. Rial, Marisa Fernandez, Natalia Milduberger, Carolina Gonzalez, Patricia L. Bustos, Laura E. Fichera, Susana A. Laucella, Maria Cecilia Albareda, Jacqueline Bua
Summary: This study found that Trypanosoma cruzi, the causative agent of Chagas disease, secretes a 19kDa cyclophilin called TcCyP19, which is recognized by sera from infected mice and patients. The levels of anti-TcCyP19 antibodies significantly decreased in treated mice in the acute and chronic phase of infection, as well as in chronically infected individuals after 12 months of treatment. These findings suggest that TcCyP19 could serve as an early biomarker for the efficiency of trypanocidal treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Gulsel Yurtdas-Kirimlioglu
Summary: This study aimed to develop hard-cellulose capsules containing CEF loaded P127/PVP SDs using an ultrasonic probe induced solvent-lyophilization method for improved antibacterial treatment. The SDs showed increased solubility and lower MIC values compared to pure CEF, with significantly faster release rates. These SDs present a feasible alternative for effective antibacterial therapy with lower doses.
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Yi Guo, Henis Patel, Aishwarya Saraswat, Kranthi Venkat Mateti, Ketan Patel, Emilio Squillante
Summary: This research aimed to enhance the solubility and dissolution rate of poorly-water soluble and heat-labile drug albendazole (ABZ) using supercritical fluid (SCF) technology. Polymer screening and solid state characterization were conducted to optimize the process and product. The results showed that the SCF batches processed at 80 degrees C, 1500 psi and 2 h resulted in substantial amorphization of ABZ, leading to improved dissolution. The SCF formulation also showed enhanced permeability compared to pure ABZ.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2023)
Article
Pharmacology & Pharmacy
Hongwei Zhang, Minglu Li, Jianmin Li, Anjali Agrawal, Ho-Wah Hui, Demin Liu
Summary: This study compared the performance of two amorphous formulation strategies: mesoporous silica via solvent impregnation, and solid dispersions by spray drying. The results showed that mesoporous silica was able to maintain amorphous fenofibrate for up to 3 months and had better flowability compared to solid dispersions. In vitro dissolution results indicated a well-controlled release of fenofibrate from mesoporous silica. This study demonstrates the potential of mesoporous silica as an alternative formulation platform to spray-dried solid dispersions for oral drug product development.
Article
Chemistry, Multidisciplinary
Guojia Yu, Xinjian Chen, Lichao He, Xiangrong Li, Zhiyong Zhou, Zhongqi Ren
Summary: The solubility of insoluble telmisartan was improved by forming new cocrystal forms with several aromatic carboxylic acids. All solid forms showed three dissolution modes, with TEL-HBA achieving maximum release equilibrium within 30 minutes. The most stable form was the TEL-HBA mixture, which was selected for further thermodynamic study and found to form a 1:1 complexation with HCl (0.1 M) solution.
Article
Pharmacology & Pharmacy
Yin Xiao, Meijing Yu, Tingyu Jin, Xingyi Zhu
Summary: Solid dispersions of indomethacin with different excipients were prepared by mechanical ball milling to improve the solubility and dissolution rate of indomethacin. The results showed that the solubility and dissolution rate of indomethacin in solid dispersions were significantly improved, and hydroxypropyl methylcellulose acetate succinate was selected as the optimal excipient.
LATIN AMERICAN JOURNAL OF PHARMACY
(2021)
Article
Medicine, Research & Experimental
Kristen N. Kelsall, Leila M. Foroughi, Derek S. Frank, Luke Schenck, Anthony LaBuda, Adam J. Matzger
Summary: The polymers used in amorphous solid dispersions have an influence on the drug loading, solubility, dissolution rate, and physical stability of crystalline drugs with low solubility. In this study, the hydrophobicity of crosslinked polyethylenimine (PEI) was investigated for the delivery of the BCS class II drug flufenamic acid. Synthetic variables for crosslinking PEI were manipulated, and benzoyl chloride was employed to increase the hydrophobicity of the crosslinked materials. The findings showed enhanced drug delivery and physical stability in acidic media, motivating the use of polymers with high functional group concentrations for ASD formation.
MOLECULAR PHARMACEUTICS
(2023)
Article
Chemistry, Multidisciplinary
Smruti Rekha Rout, Gowtham Kenguva, Lopamudra Giri, Rambabu Dandela
Summary: This study successfully synthesized nine new domperidone salts using mechanochemistry and solution crystallization methods. It was found that most of the domperidone salts had higher solubility compared to the parent drug, with domperidone·adipic acid salt having the highest solubility.
Article
Parasitology
Cristina Fonseca-Berzal, Cristiane Franca da Silva, Denise da Gama Jaen Batista, Gabriel Melo de Oliveira, Jose Cumella, Marcos Meuser Batista, Raiza Brandao Peres, Aline Silva da Gama Nefertiti, Jose A. Escario, Alicia Gomez-Barrio, Vicente J. Aran, Maria de Nazare Correia Soeiro
Article
Pharmacology & Pharmacy
Carlos Torrado-Salmeron, Victor Guarnizo-Herrero, Teresa Gallego-Arranz, Yvonne del Val-Sabugo, Guillermo Torrado, Javier Morales, Santiago Torrado-Santiago
Article
Biophysics
Teresa Gallego-Arranz, Alba Perez-Cantero, Carlos Torrado-Salmeron, Victor Guarnizo-Herrero, Javier Capilla, Santiago Torrado-Duran
COLLOIDS AND SURFACES B-BIOINTERFACES
(2020)
Article
Chemistry, Medicinal
Alexandra Ibanez-Escribano, Felipe Reviriego, Nerea Vela, Cristina Fonseca-Berzal, Juan Jose Nogal-Ruiz, Vicente J. Aran, Jose Antonio Escario, Alicia Gomez-Barrio
Summary: A series of compounds with trichomonacidal activity were synthesized and two of them showed better efficacy compared to the reference drug, with high activity against resistant isolates as well.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Pharmacology & Pharmacy
Carlos Torrado-Salmeron, Victor Guarnizo-Herrero, Joana Henriques, Raquel Seica, Cristina M. Sena, Santiago Torrado-Santiago
Summary: This study aimed to develop multiparticulate systems with ezetimibe and atorvastatin, showing promising results in diabetic rats by reducing hyperlipidemia and hepatic steatosis.
Article
Chemistry, Medicinal
Carlos Benavent, Carlos Torrado-Salmeron, Santiago Torrado-Santiago
Summary: This study aimed to improve the treatment of Candida albicans biofilms by developing nystatin solid dispersions using maltodextrins as a hyperosmotic carrier. The results showed that the antifungal activity was enhanced, and biofilm formation was significantly reduced by the elaboration process and physicochemical properties of the SD-N:MD [1:6] formulation, suggesting a promising strategy for treating Candida biofilms.
Article
Biochemistry & Molecular Biology
Alexandra Ibanez-Escribano, Cristina Fonseca-Berzal, Monica Martinez-Montiel, Manuel Alvarez-Marquez, Maria Gomez-Nunez, Manuel Lacueva-Arnedo, Teresa Espinosa-Buitrago, Tania Martin-Perez, Jose Antonio Escario, Penelope Merino-Montiel, Sara Montiel-Smith, Alicia Gomez-Barrio, Oscar Lopez, Jose G. Fernandez-Bolanos
Summary: In this study, a series of antiprotozoal compounds were synthesized by modifying the substituents on N-1 and N-4 and the nature of the chalcogen atom. The compounds showed good activity against Trypanosoma cruzi and Trichomonas vaginalis. Thiosemicarbazide 31 exhibited the best trypanocidal activity, while thiosemicarbazones 49, 51, and 63 showed remarkable trichomonacidal effects. The compounds were also found to be non-toxic to mammalian cells.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Parasitology
Ruben Martin-Escolano, Gregorio Perez-Cordon, Vicente J. Aran, Clotilde Marin, Manuel Sanchez-Moreno, Maria Jose Rosales
Summary: This study evaluated the activity of 10 5-nitroindazole derivatives against Acanthamoeba. The results showed the effectiveness of these compounds against both trophozoites and cysts, with derivative 8 showing the highest activity on cysts. These 5-nitroindazole derivatives may be a promising alternative for more efficient treatments against A. castellani infection.
Article
Parasitology
Cristina Fonseca-Berzal, Alexandra Ibanez-Escribano, Sonia de Castro, Jose A. Escario, Alicia Gomez-Barrio, Vicente J. Aran
Summary: In this study, a new series of 5-nitroindazole derivatives and a related 6-nitroquinazoline were synthesized and evaluated for their inhibitory effects against the kinetoplastid parasite Trypanosoma cruzi. Some of these derivatives showed better trypanocidal activity than the reference drug benznidazole and exhibited selective toxicity towards the parasite. Furthermore, these compounds also demonstrated inhibitory effects on the intracellular replicative form of the parasite. The results suggest that the introduction of electron withdrawing substituents can enhance the trypanocidal activity of these compounds.
Article
Pharmacology & Pharmacy
Carlos Torrado-Salmeron, Victor Guarnizo-Herrero, Guillermo Torrado, M. Angeles Pena, Santiago Torrado-Santiago, Paloma Marina de la Torre-Iglesias
Summary: Atorvastatin, a lipid-lowering drug with low solubility, was formulated into solid dispersions and micellar systems to improve its therapeutic efficacy. Solid dispersions with croscarmellose sodium as a carrier were developed. The addition of Kolliphor (R) RH40 surfactant in the solid dispersions enhanced intermolecular hydrogen bonding between the drug and polymer chains, while the micellar system with Kolliphor (R) RH40 promoted delayed recrystallization.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Chemistry, Medicinal
J. Jonathan Nue-Martinez, David Cisneros, Maria del Valle Moreno-Blazquez, Cristina Fonseca-Berzal, Jose Ignacio Manzano, Damien Kraeutler, Marzuq A. Ungogo, Maha A. Aloraini, Hamza A. A. Elati, Alexandra Ibanez-Escribano, Laura Lagartera, Tomas Herraiz, Francisco Gamarro, Harry P. de Koning, Alicia Gomez-Barrio, Christophe Dardonville
Summary: In this study, we synthesized a series of analogues and conducted antiprotozoal screening and SAR studies of kDNA binders for trypanosomatid parasites. We found that compound 3a exhibited good activity and selectivity against all three parasites, making it a promising candidate for in vivo studies.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Polymer Science
Celia Lopez-Manzanara Perez, Norma Sofia Torres-Pabon, Almudena Laguna, Guillermo Torrado, Paloma de la Torre-iglesias, Santiago Torrado-Santiago, Carlos Torrado-Salmeron
Summary: This study developed polyelectrolyte complexes (PEC) to enhance the dissolution rate of simvastatin (SIM). The PEC-SIM:CS:CMC (1:2:1) complex showed improved dissolution behavior, which could be attributed to the relaxation of polymer chains and an increase in intramolecular hydrogen bonds.
Article
Polymer Science
Victor Guarnizo-Herrero, Carlos Torrado-Salmeron, Norma Sofia Torres Pabon, Guillermo Torrado Duran, Javier Morales, Santiago Torrado-Santiago
Summary: This study investigated the use of different proportions of cationic chitosan and anionic carboxymethyl cellulose in developing polyelectrolyte complexes for sustained-release systems. The analysis confirmed that these complexes enhanced drug encapsulation and enabled prolonged drug release, with a transport mechanism controlled by Fickian diffusion.
Article
Pharmacology & Pharmacy
Greta Camilla Magnano, Marika Quadri, Elisabetta Palazzo, Roberta Lotti, Francesca Loschi, Stefano Dall'Acqua, Michela Abrami, Francesca Larese Filon, Alessandra Marconi, Dritan Hasa
Summary: This study aimed to investigate the loading of sildenafil citrate in three commercial transdermal vehicles using 3D full-thickness skin equivalent and compare the results with permeability experiments using porcine skin. The results showed that the results obtained using the 3D skin equivalent were comparable to those obtained using porcine skin, suggesting that the 3D skin model can be a valid alternative for ex-vivo skin absorption experiments.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2024)
Article
Pharmacology & Pharmacy
James W. Mckeage, Andrew Z. H. Tan, Andrew J. Taberner
Summary: Needle-free jet injection is a promising alternative drug delivery technique that offers rapid, non-invasive, and large-volume injections. The study presents a prototype multi-orifice nozzle and a computational fluid dynamic model to demonstrate the feasibility and effectiveness of this technology.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2024)