RESUMO
Sweet basil (Ocimum basilicum) leaves are rich in bioactive compounds that present therapeutic benefits for human health. Ultrasonic-assisted extraction (UAE) is frequently used to obtain phenolic compounds from plants/herbal sources. However, few works have developed multi-variable studies to find the optimal conditions to extract the maximum amount of compounds, especially when applied to UAE via a sonotrode. The purpose of this work was to perform a multi-variable study by employing a Box-Behnken design to collect the highest active compound content from Ocimum basilicum leaves. The efficacy of the design was endorsed by ANOVA. The studied parameters for UAE via a sonotrode were the ethanol/water ratio, amplitude, and time. The analyzed responses were the rosmarinic acid, the sum of phenolic acids, and the sum of phenolic compounds content. The optimal conditions were found to be 50% ethanol/water, 50% amplitude, and 5 min. Twenty bioactive compounds were identified by HPLC-ESI-TOF-MS when the extract was collected by applying the optimal conditions. Ocimum basilicum may be appreciated as a valuable source of important bioactive substances for pharmaceutical use.
Assuntos
Ocimum basilicum , Humanos , Antioxidantes , Fenóis , Folhas de Planta , Etanol , ÁguaRESUMO
Aim: A solid self-emulsifying drug delivery systems was developed by using the spray-drying technique, to improve the solubility of resveratrol (RES). Materials & methods: Cod liver oil and three surfactant system were tested: soy phosphatidylcholine (SPC)/Eumulgin® HRE-40 (EU)/Sodium oleate (system A); SPC/Tween®80 (TW) /Sodium oleate (system B) and SPC/EU/TW (system C). Results: The greatest incorporation was obtained with system C (21.26 mg/ml). Solid self-emulsifying drug delivery systems with the highest yield were obtained with colloidal silicon dioxide (CSD) (80.12%), and CSD sodium croscarmelose 9:1 and 5:5. RES dissolution attained 100% at 45 min with CSD:CS 5:5. Discussion: The surface modification to hydrophilic by CSD:sodium croscarmellose reduced the cohesive force among drug particles. Conclusion: The developed systems are a good approximation for the design of strategies that could allow increasing the oral bioavailability of RES.
Assuntos
Composição de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/métodos , Desenvolvimento de Medicamentos , Excipientes/química , Resveratrol/administração & dosagem , Administração Oral , Carboximetilcelulose Sódica/química , Química Farmacêutica , Emulsões , Interações Hidrofóbicas e Hidrofílicas , Resveratrol/química , Dióxido de Silício/química , SolubilidadeRESUMO
AIM: Binary and ternary complexes with hydroxypropyl-ß-cyclodextrin (HPßCD), using glutamic acid (GA), proline or lysine as the third component, were developed to increase the solubility and the dissolution rate of norfloxacin (NOR). METHODS/RESULTS: Complexation was evaluated by phase solubility studies, obtaining the highest NOR solubility with GA and HPßCD. Thermal analysis suggested that different kinds of interactions occur among NOR, HPßCD and each amino acid, and when the systems were prepared by kneading or by means of freeze-drying technique. Dissolution studies, performed on simulated gastric fluid and subsequent simulated intestinal fluid, showed the highest rate of NOR from NOR-HPßCD-GA. CONCLUSION: NOR:HPßCD:GA was the best approach for improving the bioavailability of NOR.
Assuntos
Antibacterianos/farmacocinética , Portadores de Fármacos/química , Composição de Medicamentos/métodos , Norfloxacino/farmacocinética , 2-Hidroxipropil-beta-Ciclodextrina/química , Antibacterianos/administração & dosagem , Antibacterianos/química , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Química Farmacêutica , Liberação Controlada de Fármacos , Liofilização , Ácido Glutâmico/química , Norfloxacino/administração & dosagem , Norfloxacino/química , Solubilidade , beta-Ciclodextrinas/químicaRESUMO
The aim of this work was to predict the permeability of two model drugs, sulfamerazine (SMR) and indomethacin (INM), and to determine the effect on their apparent permeabilities by complexation with cyclodextrins and/or meglumine or incorporation in microemulsions. Permeation experiments were performed using two-chamber diffusion cells with a new composition of bio-mimetic membrane composed of 80% of Lipoid® S100 and 20% of cholesterol in n-octanol 10% w/w solution, at 37 ± 0.5°C and 14,000 rpm. The predictive capacity of the permeability of passive diffusion absorbed compounds was evaluated using 20 drug standards and showed an exponential correlation between the apparent permeability coefficients (Papp) and the fraction absorbed percentages in humans (Fa%), with an R2 value of 0.67942 and a constant value of - 4.1 ± 0.8. SMR and INM were classified as Class II and I, respectively, according to the Biopharmaceutical Classification System. These drugs were complexed and incorporated in microemulsions. The Fa% from all the drug products was higher than 90%. SMR in the complexes and both drugs in microemulsions were classified as highly soluble. Thus, SMR and INM incorporated in these pharmaceutical products could be classified as Class I.
Assuntos
Materiais Biomiméticos/química , Materiais Biomiméticos/farmacocinética , Emulsões/química , Emulsões/farmacocinética , Membranas Artificiais , Biomimética/métodos , Ciclodextrinas/química , Ciclodextrinas/farmacocinética , Difusão , Indometacina/química , Indometacina/farmacocinética , Permeabilidade/efeitos dos fármacos , SolubilidadeRESUMO
Norfloxacin, an antibiotic that exists in different solid forms, has very unfavorable properties in terms of solubility and stability. Binary complexes of norfloxacin, in the solid form C, and ß-cyclodextrin were procured by the kneading method and physical mixture. Their effect on the solubility, the dissolution rate, and the chemical and physical stability of norfloxacin was evaluated. To perform stability studies, the solid samples were stored under accelerated storage conditions, for a period of 6 months. Physical stability was monitored through powder X-ray diffraction, high-resolution 13C solid-state nuclear magnetic resonance, and scanning electron microscopy. The results showed evidence that the kneaded complex increased and modulated the dissolution rate of norfloxacin C. Furthermore, it was demonstrated that the photochemical stability was increased in the complex, without affecting its physical stability. The results point to the conclusion that the new kneading complex of norfloxacin constitutes an alternative tool to formulate a potential oral drug delivery system with improve oral bioavailability.
Assuntos
Antibacterianos/química , Antibacterianos/metabolismo , Norfloxacino/química , Norfloxacino/metabolismo , beta-Ciclodextrinas/química , beta-Ciclodextrinas/metabolismo , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Sistemas de Liberação de Medicamentos , Estabilidade de Medicamentos , Espectroscopia de Ressonância Magnética , Microscopia Eletrônica de Varredura , Sequestrantes/química , Sequestrantes/metabolismo , Solubilidade , Difração de Raios XRESUMO
We propose an in vitro permeability assay by using a modified lipid membrane to predict the in vivo intestinal passive permeability of drugs. Two conditions were tested, one with a gradient pH (pH 5.5 donor/pH 7.4 receptor) and the other with an iso-pH 7.4. The predictability of the method was established by correlating the obtained apparent intestinal permeability coefficients (Papp) and the oral dose fraction absorbed in humans (fa) of 16 drugs with different absorption properties. The Papp values correlated well with the absorption rates under the two conditions, and the method showed high predictability and good reproducibility. On the other hand, with this method, we successfully predicted the transport characteristics of oral sulfadiazine (SDZ). Also, the tradeoff between the increase in the solubility of SDZ by its complex formation with cyclodextrins and/or aminoacids and its oral permeability was assessed. Results suggest that SDZ is transported through the gastrointestinal epithelium by passive diffusion in a pH-dependent manner. These results support the classification of SDZ as a high/low borderline permeability compound and are in agreement with the Biopharmaceutics Classification Systems (BCS). This conclusion is consistent with the in vivo pharmacokinetic properties of SDZ.
Assuntos
Ciclodextrinas/química , Absorção Intestinal , Sulfadiazina/metabolismo , Administração Oral , Transporte Biológico , Permeabilidade da Membrana Celular , Difusão , Humanos , Concentração de Íons de Hidrogênio , Metabolismo dos Lipídeos , Membranas Artificiais , Reprodutibilidade dos Testes , Solubilidade , Sulfadiazina/administração & dosagem , Sulfadiazina/química , Sulfadiazina/farmacocinéticaRESUMO
The purpose of this study was to investigate the effect on solubility and dissolution rate of binary complexes of ß-(ßCD), methyl-(MßCD) and hydroxypropyl-ß-cyclodextrin (HPßCD) with diloxanide furoate (DF). The complexation in solution was evaluated by phase solubility studies and 1H nuclear magnetic resonance (NMR). Enhanced water solubility of DF was obtained with the DF:MßCD system (61-fold). The mode of inclusion was supported by NMR experiments, which indicated that real inclusion complexes were formed between DF and MßCD or HPßCD. Solid state analysis was performed using infrared and thermal methods, which suggested the formation of true inclusion complexes of DF with two derivatized cyclodextrins, MßCD and HPßCD, and an exclusion complex with ßCD when the systems were prepared by freeze-dried technique. Dissolution studies conducted in simulated gastric fluid (2 h) and subsequent simulated intestinal fluid (next 4 h) showed increased dissolution rate of DF from the freeze-dried systems with ßCD, MßCD, and HPßCD (85; 77 and 75% of dissolved drug at 5 min, respectively) and 100% of the drug dissolved at 150 min for the three systems. The enhancement of the solubility and the dissolution of DF observed make these complexes promising candidates for the preparation of oral pharmaceutical formulations.
Assuntos
2-Hidroxipropil-beta-Ciclodextrina/química , Amebicidas/química , Excipientes/química , Furanos/química , beta-Ciclodextrinas/química , Administração Oral , Amebicidas/administração & dosagem , Composição de Medicamentos , Furanos/administração & dosagem , Humanos , Transição de Fase , SolubilidadeRESUMO
Cyclodextrins (CDs) and meglumine (MEG) are pharmaceutical excipients widely used to improve solubility of poorly water-soluble drugs. The purpose of this work was to study the effect of CDs or MEG on the internal microstructure of soya oil-based O/W microemulsions (MEs) and on the modulation of the solubility and release rate of Class II model hydrophobic drugs, sulfamerazine and indomethacin. The pseudoternary phase diagrams revealed that higher proportions of oil phase, as well as the presence of ß-cyclodextrin (ßCD), methyl-ßCD, and MEG, favored the incorporation of the drugs. The conductivity studies, particle size, and zeta potential analysis showed that the O/W ME structure remained unaffected and that the ME presented reduced droplet sizes after the incorporation of the ligands. The drug-component interactions were assessed by proton nuclear magnetic resonance studies. The highest incorporations of sulfamerazine (35.6 mg/mL) and indomethacin (73.1 mg/mL) were obtained with the ME with W = 5%, MEG and W = 1.8% ßCD in a phosphate buffer solution of pH 8, respectively. In addition, the ligands in ME significantly enhanced the released amount of the drugs, probably due to a solubilizing effect that facilitates the drug to penetrate the unstirred water layer adjacent to membranes.
Assuntos
Sistemas de Liberação de Medicamentos , Emulsões/química , Meglumina/química , beta-Ciclodextrinas/química , Algoritmos , Condutividade Elétrica , Excipientes , Indometacina/química , Cinética , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Tamanho da Partícula , Solubilidade , Sulfamerazina/químicaRESUMO
The aim of this work was the development and characterization of a biocompatible microemulsion (ME) containing soybean oil (O), phosphatidylcholine/sodium oleate/Eumulgin®HRE40 as the surfactant mixture (S) and water or buffer solution as the aqueous phase (W), for oral delivery of the poorly water-soluble drugs sulfamerazine (SMR) and indomethacin (INM). A wide range of combinations to obtain clear oil-in-water (o/w) ME was observed from pseudo-ternary phase diagrams, which was greater after the incorporation of both drugs, suggesting that they acted as stabilizers. Drug partition studies indicated a lower affinity of the drugs for the oil domain when they were ionized and with increased temperature, explained by the fact that both drugs were introduced inside the oil domain, determined by nuclear magnetic resonance. High concentrations of SMR and INM were able to be incorporated (22.0 and 62.3 mg/mL, respectively). The ME obtained presented an average droplet size of 100 nm and a negative surface charge. A significant increase in the release of SMR was observed with the ME with the highest percentage of O, because of the solubilizing properties of the ME. Also, a small retention effect was observed for INM, which may be explained by the differences in the partitioning properties of the drugs.