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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. [ABSTRACT FROM AUTHOR]

The aim of this work was to develop self-microemulsifying lipid-based formulations of trans-resveratrol in cod liver oil, a long chain lipid, to increase its solubility, dissolution rate and oral bioavailability. Ternary phase diagrams of cod liver oil with surfactant and water as well as pseudo-ternary phase diagrams of the same by mixing cod liver oil (triglyceride) with glycerol monooleate (monoglyeride) were constructed to identify regions where microemulsions were formed. Kolliphor RH 40, Tween 80 and their 1:1-mixtures were evaluated as surfactants. No organic cosolvents were added. It was observed that cod liver oil alone did not form microemulsion with any of the surfactants used, and a 1:1 mixture of cod liver oil and glycerol monooleate was necessary to enable the formation of microemulsion. Among the surfactants, Kolliphor RH 40 provided the maximum microemulsification effect. Several formulations containing 6:4, 1:1, and 4:6 w/w ratios of lipid to surfactant using the 1:1 mixture of cod liver oil and glycerol monooleate as lipid components and Kolliphor RH 40 or its mixture with Tween 80 as surfactants were identified, and trans-resveratrol solubility in these formulations were determined. Drug concentrations used in the formulations were 80% of saturation solubility, and no organic cosolvents were used in any formulations to increase drug solubility or enable emulsification. In vitro dispersion testing in 250 mL of 0.01 N HCl (pH 2) according to the USP method 2 at 50 RPM showed that the formulations rapidly dispersed in aqueous media forming microemulsions and there was no drug precipitation. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the effect on solubility and dissolution rate of binary complexes of β-(βCD), methyl-(MβCD) and hydroxypropyl-β-cyclodextrin (HPβCD) 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:MβCD system (61-fold). The mode of inclusion was supported by NMR experiments, which indicated that real inclusion complexes were formed between DF and MβCD or HPβCD. Solid state analysis was performed using infrared and thermal methods, which suggested the formation of true inclusion complexes of DF with two derivatized cyclodextrins, MβCD and HPβCD, and an exclusion complex with βCD 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 βCD, MβCD, and HPβCD (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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 β-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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In order to investigate the effect on the aqueous solubility and release rate of sulfamerazine (SMR) as model drug, inclusion complexes with β-cyclodextrin (βCD), methyl-β-cyclodextrin (MβCD) and hydroxypropyl-β-cyclodextrin (HPβCD) and a binary system with meglumine (MEG) were developed. The formation of 1:1 inclusion complexes of SMR with the CDs and a SMR:MEG binary system in solution and in solid state was revealed by phase solubility studies (PSS), nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FT-IR), thermal analysis and X-Ray diffractometry (XRD) studies. The CDs solubilization of SMR could be improved by ionization of the drug molecule through pH adjustments. The higher apparent stability constants of SMR:CDs complexes were obtained in pH 2.00, demonstrating that CDs present more affinity for the unionized drug. The best approach for SMR solubility enhancement results from the combination of MEG and pH adjustment, with a 34-fold increment and a Smax of 54.8 mg/ml. The permeability of the drug was reduced due to the presence of βCD, MβCD, HPβCD and MEG when used as solubilizers. The study then suggests interesting applications of CD or MEG complexes for modulating the release rate of SMR through semipermeable membranes. [ABSTRACT FROM AUTHOR]