Solid dispersions with hydrogenated castor oil increase solubility, dissolution rate and intestinal absorption of praziquantel

The solubility behavior of drugs remains one of the most challenging aspects in formulation development. Solid Dispersion (SD) has tremendous potential for improving drug solubility. Although praziquantel (PZQ) is the first drug of choice in the treatment of schistosomiasis, its poor solubility has restricted its delivery oral route. In spite of its poor solubility, PZQ is well absorbed in the gastrointestinal tract, but large doses are required to achieve adequate concentration at the target sites. The aim of this study was to improve the solubility and dissolution rate of PZQ and to evaluate its intestinal absorption. SDs were formulated with PEG-60 castor oil hydrogenated (CR-60) using a fusion and evaporation method. Pure PZQ and physical mixtures (PM) and PZQ-CR-60 (2:1; 1:1; 1:2 ratios) were compared as regards their solubility, dissolution and intestinal absorption. The experimental results demonstrated the improvement in the solubility, dissolution rate and intestinal absorption. In addition, the solubility behavior showed pH dependency and that the solubility of PZQ was slower in acidic medium than in neutral and basic mediums. The increase in PZQ solubility of the SD with the CR-60 could be attributed to several factors such as improved wettability, local solubilization, drug particle size reduction and crystalline or, interstitial solid solution reduction.A solubilidade de fármacos ainda é um dos principais desafios no desenvolvimento de formulações farmacêuticas. As dispersões sólidas (DS) apresentam grande potencial para melhorar a solubilidade de fármacos. O praziquantel é o fármaco de primeira escolha no tratamento da esquistossomose, contudo a baixa solubilidade em água restringe seu uso à administração pela via oral. Apesar da baixa solubilidade, o PZQ é bem absorvido através do trato gastrintestinal, mas doses orais elevadas são requeridas para garantir concentrações suficientes de fármaco para o tecido alvo. O objetivo deste estudo foi melhorar a solubilidade, a dissolução e avaliar a absorção do PZQ. As DS foram formuladas com óleo de castor hidrogenado - PEG 60 (CR-60), pelo uso dos métodos de fusão e evaporação do solvente. PZQ puro, mistura física (MF) e DS de CR-60-PZQ (1:2; 1:1; 2:1) foram comparados quanto à solubilidade, dissolução e absorção intestinal. Os resultados experimentais mostraram aumento na solubilidade, na taxa de dissolução e na absorção intestinal do PZQ nas DS. A solubilidade do PZQ foi maior em meio ácido, mostrando uma dependência do pH. O aumento na solubilidade do PZQ nas DS com CR-60 foi atribuída a fatores como aumento da molhabilidade, solubilização local, redução granulométrica e redução da cristalinidade ou, ainda, a ocorrência de uma solução sólida intersticial

Solid dispersions with hydrogenated castor oil increase solubility, dissolution rate and intestinal absorption of praziquantel

The solubility behavior of drugs remains one of the most challenging aspects in formulation development. Solid Dispersion (SD) has tremendous potential for improving drug solubility. Although praziquantel (PZQ) is the first drug of choice in the treatment of schistosomiasis, its poor solubility has restricted its delivery oral route. In spite of its poor solubility, PZQ is well absorbed in the gastrointestinal tract, but large doses are required to achieve adequate concentration at the target sites. The aim of this study was to improve the solubility and dissolution rate of PZQ and to evaluate its intestinal absorption. SDs were formulated with PEG-60 castor oil hydrogenated (CR-60) using a fusion and evaporation method. Pure PZQ and physical mixtures (PM) and PZQ-CR-60 (2:1; 1:1; 1:2 ratios) were compared as regards their solubility, dissolution and intestinal absorption. The experimental results demonstrated the improvement in the solubility, dissolution rate and intestinal absorption. In addition, the solubility behavior showed pH dependency and that the solubility of PZQ was slower in acidic medium than in neutral and basic mediums. The increase in PZQ solubility of the SD with the CR-60 could be attributed to several factors such as improved wettability, local solubilization, drug particle size reduction and crystalline or, interstitial solid solution reduction.A solubilidade de fármacos ainda é um dos principais desafios no desenvolvimento de formulações farmacêuticas. As dispersões sólidas (DS) apresentam grande potencial para melhorar a solubilidade de fármacos. O praziquantel é o fármaco de primeira escolha no tratamento da esquistossomose, contudo a baixa solubilidade em água restringe seu uso à administração pela via oral. Apesar da baixa solubilidade, o PZQ é bem absorvido através do trato gastrintestinal, mas doses orais elevadas são requeridas para garantir concentrações suficientes de fármaco para o tecido alvo. O objetivo deste estudo foi melhorar a solubilidade, a dissolução e avaliar a absorção do PZQ. As DS foram formuladas com óleo de castor hidrogenado - PEG 60 (CR-60), pelo uso dos métodos de fusão e evaporação do solvente. PZQ puro, mistura física (MF) e DS de CR-60-PZQ (1:2; 1:1; 2:1) foram comparados quanto à solubilidade, dissolução e absorção intestinal. Os resultados experimentais mostraram aumento na solubilidade, na taxa de dissolução e na absorção intestinal do PZQ nas DS. A solubilidade do PZQ foi maior em meio ácido, mostrando uma dependência do pH. O aumento na solubilidade do PZQ nas DS com CR-60 foi atribuída a fatores como aumento da molhabilidade, solubilização local, redução granulométrica e redução da cristalinidade ou, ainda, a ocorrência de uma solução sólida intersticial.(CNPq) National Council of Scientific and Technological Development(FAPESP) São Paulo Research Foundatio

Preparation and evaluation of modified release zidovudine tablets

Zidovudine is a drug used for the treatment of AIDS. The objective of this work was to prepare tablets for modified release of zidovudine. Hydroxypropyl methylcellulose HPMC K100LV and HPMC K4M at 12.50 %, 18.75 % and 25.00 % were used. The tablets produced with 12.50 % of HPMC reached 100 % of the zidovudine release in 6 hours, while those produced with 18.75 and 25.00 %, released 24 h, following the Higuchi and First Order kinetic models, respectively. The calculated release exponent pointed out that formulations follow the anomalous type of release mechanism, with a combined phenomena of diffusion and erosion.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Assessment of solubility and intestinal absorption in vitro of praziquantel in solid dispersions of polyethylene glycol 6000

The aim of this study was to investigate the impact of solid dispersions of polyethylene glycol 6000 (PEG 6000), using the co-precipitation method, on the in vitro solubility and intestinal absorption of praziquantel (PZQ). The solubility of PZQ in solid dispersions and physical mixtures was assessed in purified water and TC-199 buffer. The everted intestinal sac model was employed to assess, in vitro, intestinal absorption of PZQ. A significant enhancement in both in vitro solubility and intestinal absorption of PZQ was found in solid dispersions compared to pure PZQ and physical mixtures. This positive series of preliminary results showed that solid dispersion of PEG 6000 is a valuable strategy for increasing bioavailability of PZQ and could also prove useful for other poorly water-soluble drugs.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Effect of polysaccharide sources on the physicochemical properties of bromelainchitosan nanoparticles

Bromelain, a set of proteolytic enzymes potential pharmaceutical applications, was encapsulated in chitosan nanoparticles to enhance enzyme stability, and the effect of different chitosan sources was evaluated. Chitosan types (i.e., low molecular weight chitosan, chitosan oligosaccharide lactate, and chitosan from shrimp shells) produced nanoparticles with different physicochemical properties, however in all cases, particle size and zeta potential decreased, and polydispersity index increased after bromelain addition. Bromelain encapsulation was higher than 84% and 79% for protein content and enzymatic activity, respectively, with low molecular weight chitosan presenting the highest encapsulation efficiency. Nanoparticle suspension was also tested for accelerated stability and rheological behavior. For the chitosan–bromelain nanoparticles, an instability index below 0.3 was recorded and, in general, the loading of bromelain in chitosan nanoparticles decreased the cohesiveness of the final suspension.This research was granted by FAPESP (2016/03444-5,2017/05275-9,and2017/05333-9), CNPq and FAEPEX, and by the Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT/MEC) through national funds, and co-financed by FEDER, under the project reference M-ERA-NET/0004/2015 (PAIRED) Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

Assessment of solubility and intestinal absorption in vitro of praziquantel in solid dispersions of polyethylene glycol 6000

The aim of this study was to investigate the impact of solid dispersions of polyethylene glycol 6000 (PEG 6000), using the co-precipitation method, on the in vitro solubility and intestinal absorption of praziquantel (PZQ). The solubility of PZQ in solid dispersions and physical mixtures was assessed in purified water and TC-199 buffer. The everted intestinal sac model was employed to assess, in vitro, intestinal absorption of PZQ. A significant enhancement in both in vitro solubility and intestinal absorption of PZQ was found in solid dispersions compared to pure PZQ and physical mixtures. This positive series of preliminary results showed that solid dispersion of PEG 6000 is a valuable strategy for increasing bioavailability of PZQ and could also prove useful for other poorly water-soluble drugs.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Silver nanoparticles-composing alginate/gelatine hydrogel improves wound healing in vivo

Polymer hydrogels have been suggested as dressing materials for the treatment of cutaneous wounds and tissue revitalization. In this work, we report the development of a hydrogel composed of natural polymers (sodium alginate and gelatin) and silver nanoparticles (AgNPs) with recognized antimicrobial activity for healing cutaneous lesions. For the development of the hydrogel, different ratios of sodium alginate and gelatin have been tested, while different concentrations of AgNO3 precursor (1.0, 2.0, and 4.0 mM) were assayed for the production of AgNPs. The obtained AgNPs exhibited a characteristic peak between 430450 nm in the ultraviolet-visible (UVVis) spectrum suggesting a spheroidal form, which was confirmed by Transmission Electron Microscopy (TEM). Fourier Transform Infra-red (FTIR) analysis suggested the formation of strong intermolecular interactions as hydrogen bonds and electrostatic attractions between polymers, showing bands at 2920, 2852, 1500, and 1640 cm1. Significant bactericidal activity was observed for the hydrogel, with a Minimum Inhibitory Concentration (MIC) of 0.50 µg/mL against Pseudomonas aeruginosa and 53.0 µg/mL against Staphylococcus aureus. AgNPs were shown to be non-cytotoxic against fibroblast cells. The in vivo studies in female Wister rats confirmed the capacity of the AgNP-loaded hydrogels to reduce the wound size compared to uncoated injuries promoting histological changes in the healing tissue over the time course of wound healing, as in earlier development and maturation of granulation tissue. The developed hydrogel with AgNPs has healing potential for clinical applications.This research received funding from the Coordenação Aperfeiçoamento de Pessoal de Nivel Superior (CAPES), Fundação de Amparo à Pesquisa do Estado de Sergipe (FAPITEC), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, #443238/2014-6, #470388/2014-5), and from the Portuguese Science and Technology Foundation (FCT) projects M-ERA-NET/0004/2015 (PAIRED) and UIDB/04469/2020 (strategic fund).info:eu-repo/semantics/publishedVersio

Bacterial nanocellulose and fibroin: natural products to produce a structure membranes

Fibroin (FB) and bacterial nanocellulose (BC) are natural products, being used in biomedicine, electronics, food industries and other areas. Both show biocompatibility, able to be used for many different purposes. The blending of fibroin and bacterial nanocellulose was design to produce a biocompatible material to be applied with a medical device. For this reason, the objective of this work was to evaluate the structure properties of the blending of BC and FB. Thus, FB was extracted from Bombyx mori and BC was produced by fermentation process utilizing Gluconacetobacter xylinus. The membranes composed of BC-FB were produced by immersion contact for 24 hours, at 25°C, in 100rpm; without crosslinking agent. After the production the membrane samples were dried and characterized by Fourier transform infrared spectroscopy (FTIR spectroscopy), mechanical proprieties, swelling efficiency, scanning electron microscopy (SEM) and computerized microtomography (µCt). Results indicate that the hydrogen-bonded porous membranes obtained displayed anisiotropic, closed and interconnected porous morphology. The morphometric characteristics, which resemble a honeycomb and consist of a long structure with high connectivity and high total porosity, amplify the areas of BC-FB blend applications, with potential utilization with optoelectronic devices, in areas ranging from environmental to tissue engineering. Furthermore, the production by immersion contact will allow the upscale process and the development of green label material.Keywords: Polymers conjugation, Membranes; Fibroin; Bacterial nanocellulose

Correction: Diniz et al. Silver Nanoparticles-Composing Alginate/Gelatine Hydrogel Improves Wound Healing In Vivo. Nanomaterials 2020, 10, 390

In the original publication, there was a mistake in Figure 6 as published [...]info:eu-repo/semantics/publishedVersio

Flavonoid-enriched plant-extract-loaded emulsion: a novel phytocosmetic sunscreen formulation with antioxidant properties

The aim of this study was to develop a phytocosmetic sunscreen emulsion with antioxidant effect, containing a blend of flavonoid-enriched plant extracts. In vitro sun protection factor, antioxidant activity, skin irritation, photostability, cutaneous permeation, and retention of flavonoids were evaluated. Thermodynamically stable emulsions were obtained and tested for sensorial analysis after loading the blend of extracts. The selected emulsion was stable when stored at low temperatures (5 C), for which after 120 days the concentration of quercetin and rutin were above their limit of quantification, i.e., 2.8 ± 0.39 µg/mL and 30.39 ± 0.39 µg/mL, respectively. Spreadability, low rupture strength and adhesiveness were shown to be similar to a conventional topical product. Higher brittleness, pseudo-plastic, and viscoelastic behaviors were also recorded for the developed phytocosmetic sunscreen. The product presented a critical wavelength of 387.0 nm and ultraviolet rays A and B (UVA/UVB) rate of 0.78, confirming that the developed formulation shows capacity for UVA/UVB protection, protecting skin against damages caused by Ultraviolet (UV) radiation. Rutin was shown to permeate the skin barrier and was also quantified in the stratum corneum (3.27 ± 1.92 µg/mL) by tape stripping and retention test (114.68 ± 8.70 µg/mL). The developed flavonoid-enriched phytocosmetic was shown to be non-irritant to skin by an in vitro assay. Our results confirm the antioxidant activity, sun protection, and physical properties of the developed phytocosmetic for topical application.This research was funded by FAPESP (grant number 2015/25533‐7 and 2017/14757‐7), CAPES and CNPq. The authors also received support from the Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) under the project reference M‐ERA‐NET/0004/2015‐PAIRED, co‐financed by FEDER, under the Partnership Agreement PT2020, and PhD scholarship (SFRH/BD/130555/2017).info:eu-repo/semantics/publishedVersio