Search Results (9)

Background: Voriconazole is an antifungal drug, which is classified under Bio-Classification System-II and has low water solubility (0.71 mg/mL) and high permeability. Hardly any endeavors have been made to increase the bioavailability of voriconazole. Objective: To develop and evaluate a solid SMEDDS (self-microemulsifying drug delivery system) for antifungal activity. Methods: Based on solubility studies of Labrafil-M 1994 CS (oil), Cremophor-RH 40 (a surfactant) and Transcutol-HP (a co-surfactant) were selected as components of the SMEDDS and a pseudo-ternary phase diagram was prepared. Thereafter, the oil, surfactant, and co-surfactant were mixed with altered weight ratios (1:1/1:2/2:1) and evaluated through various in vitro, in vivo analyses. Results: The particle size of the optimized formulation was observed to be 19.04 nm and the polydispersity index (PDI) value was found to be 0.162 with steady-state zeta potential. The optimized liquid SMEDDS was converted into a solid SMEDDS. Various adsorbents, such as Aerosil-200, Avicel-PH101, Neusilin-US2, and Neusilin UFL2 were screened to better detect the oil-absorbing capacity and flow properties of the powder. Neusilin UFL2 was selected as an adsorbent due to its better oil-absorbing capacity. DSC, X-ray diffraction, and dissolution studies were carried out to characterize the formulation. Further, the Pharmacokinetic profile was also studied in Wistar rats and the Cmax, tmax, and AUC0→t were calculated. The Cmax and AUC0→t plasma concentration is considerably better for the SMEDDS than for the pure drug and marketed formulation. Conclusions: This investigation clearly reveals the potential of developing a solid SMEDDS for candidiasis and invasive aspergillosis treatment, with better efficacy as compared to the commercially available marketed formulation. Full article

The development of oral insulin drug delivery systems is still an ongoing challenge for pharmaceutical technology researchers, as the formulation process has to overcome a number of obstacles due to the adverse characteristics of peptides. The aim of this study was to formulate different sodium-alginate microparticles as a possible method for oral insulin administration. In our previous studies, the method has been successfully optimized using a small model peptide. The incorporation of insulin into alginate carriers containing nonionic surfactants has not been described yet. In order to enhance the absorption of insulin through biological barriers, Labrasol ALF and Labrafil M 2125 CS were selected as permeation-enhancing excipients. They were applied at a concentration of 0.10% (v/v%), along with various combinations of the two, to increase oral bioavailability. Encapsulation efficiency showed sufficient drug incorporation, as it resulted in over 80% in each composition. In vitro dissolution and enzymatic stability test results proved that, as a pH-responsive polymer, alginate bead swelling and drug release occur at higher pH, thus protecting insulin against the harsh environment of the gastrointestinal tract. The remaining insulin content was 66% due to SIF degradation after 120 min. Permeability experiments revealed the impact of permeation enhancers and natural polymers on drug absorption, as they enhanced drug transport significantly through Caco-2 cells in the case of alginate microparticle formulations, as opposed to the control insulin solution. These results suggest that these formulations are able to improve the oral bioavailability of insulin. Full article

Lipid nanocapsules (LNCs) are promising for transdermal drug delivery due to their higher permeability-enhancing effects compared to polymeric nanoparticles. Lavender oil is an essential oil consisting of several terpenes (primarily linalool and linalyl acetate) known for their profound permeation-enhancing action. In the present work, we successfully encapsulated asenapine maleate (a second-generation antipsychotic that is highly metabolized by the liver, reducing its oral bioavailability) into biocompatible LNCs for transdermal application using a novel oily phase, i.e., lavender oil (LO-LNCs). A comparative study was conducted to determine the effects of different oily phases (i.e., Miglyol^® 812, Labrafil^® M1944CS, and Labrafac™ PG) on the LNCs. Surfactant types (Kolliphor^® HS15, Kolliphor^® EL and Tween80) and oil:surfactant ratios were studied. Blank and asenapine-loaded LNCs were optimized for particle size, polydispersity index, zeta potential, drug content and ex vivo skin permeation. Lavender oil and Labrafil^® showed smaller vesicular sizes, while LO-LNCs increased the permeation of ASP across rat skin. In vivo pharmacokinetics revealed that LO-LNCs could increase the ASP C_max via transdermal application by fourfold compared to oral suspension. They increased the bioavailability of ASP by up to 52% and provided sustained release for three days. The pharmacokinetic profile of the LO-LNCs was compared to ASP-loaded invasomes (discussed in a previous study) to emphasize LNCs’ transdermal delivery behavior. Full article

Isoliquiritigenin (ILQ) has a number of biological activities such as antitumor and anti-inflammatory effects. However, biomedical applications of ILQ are impeded by its poor aqueous solubility. Therefore, in this research, we prepared a novel ILQ-loaded nanoemulsion, i.e., ILQ-NE, which consisted of Labrafil^® M 1944 CS (oil), Cremophor^® EL (surfactant), ILQ, and phosphate-buffered saline, by employing a combined sonication (high-energy) and phase-inversion composition (low-energy) method (denoted as the SPIC method). The ILQ-NE increased the ILQ solubility ~1000 times more than its intrinsic solubility. It contained spherical droplets with a mean diameter of 44.10 ± 0.28 nm and a narrow size distribution. The ILQ loading capacity was 4%. The droplet size of ILQ-NE remained unchanged during storage at 4 °C for 56 days. Nanoemulsion encapsulation effectively prevented ILQ from degradation under ultraviolet light irradiation, and enhanced the ILQ in vitro release rate. In addition, ILQ-NE showed higher cellular uptake and superior cytotoxicity to 4T1 cancer cells compared with free ILQ formulations. In conclusion, ILQ-NE may facilitate the biomedical application of ILQ, and the SPIC method presents an attractive avenue for bridging the merits and eliminating the shortcomings of traditional high-energy methods and low-energy methods. Full article

Labrafil M2125-CS is a non-ionic surfactant component widely used for improving the solubilization of poor water-soluble drugs and as component of lipid-based nanosystem formulation. The aim of this research work was to evaluate in depth the stability of lipid-based nanosystems when exposed at several experimental conditions, such as temperature- and pH-variations, and during a specific storage process—lyophilization. Dynamic light scattering was the main analysis carried out during this research work for investigating eventual physico-chemical variations of nanosystem properties after different storage phases. We demonstrated that many of prepared formulations were able to maintain almost unchanged mean size and polydispersity index values, resisting acid and basic pH or high and low temperature, as well as the freeze-drying process. Finally, the results showed that there are no univocal experimental conditions suitable for the storage of all formulation types, but each sample requires customized conditions. Full article

A novel formulation based on nanostructured lipid carriers (NLCs) was developed to increase solubility and intestinal absorption of khellin. K-NLCs were prepared with stearic acid, hempseed oil, Brij S20, and Labrafil M 1944 CS, using the emulsification-ultrasonication method. Developed nanoparticles were chemically and physically characterized by liquid chromatography, light scattering techniques, and electron microscopy. The size, about 200 nm, was optimal for oral delivery, and the polydispersity index (around 0.26), indicated high sample homogeneity. Additionally, K-NLCs showed a spherical morphology without aggregation by microscopic analysis. The encapsulation efficiency of khellin was about 55%. In vitro release studies were carried out in media with different pH to mimic physiological conditions. K-NLCs were found to be physically stable in the simulated gastric and intestinal fluids, and they preserved about 70% of khellin after 6 h incubation. K-NLCs were also successfully lyophilized testing different lyoprotectants, and obtained freeze-dried K-NLCs demonstrated good shelf life over a month. Lastly, permeability studies on Caco-2 cells were performed to predict khellin passive diffusion across the intestinal epithelium, demonstrating that nanoparticles increased khellin permeability by more than two orders of magnitude. Accordingly, developed NLCs loaded with khellin represent a versatile formulation with good biopharmaceutical properties for oral administration, possibly enhancing khellin’s bioavailability and therapeutic effects. Full article

Phillygenin, as an active ingredient of Forsythia suspensa, possesses a wide range of biological and pharmacological activity. However, its development and application are restricted due to its poor bioavailability and low solubility. Our work aimed to develop a self-microemulsifying drug delivery system to improve the oral bioavailability of phillygenin. The composition of the self-microemulsifying drug delivery system was preliminary screened by the pseudo-ternary phase diagram. Subsequently, the central composite design method was employed to optimize the prescription of the self-microemulsifying drug delivery system loaded with phillygenin. The prepared self-microemulsifying drug delivery system of phillygenin was characterized in terms of morphology, droplet size distribution, polydispersity index and stability. Then, the in vitro dissolution and the oral bioavailability were analyzed. The optimized self-microemulsifying drug delivery system of phillygenin consisted of 27.8% Labrafil M1944CS, 33.6% Cremophor EL, 38.6% polyethylene glycol 400 (PEG-400) and 10.2 mg/g phillygenin loading. The prepared self-microemulsifying drug delivery system of phillygenin exhibited spherical and uniform droplets with small size (40.11 ± 0.74 nm) and satisfactory stability. The in vitro dissolution experiment indicated that the cumulative dissolution rate of the self-microemulsifying drug delivery system of phillygenin was significantly better than that of free phillygenin. Furthermore, after oral administration in rats, the bioavailability of phillygenin was significantly enhanced by the self-microemulsifying drug delivery system. The relative bioavailability of the self-microemulsifying drug delivery system of phillygenin was 588.7% compared to the phillygenin suspension. These findings suggest that the self-microemulsifying drug delivery system of phillygenin can be a promising oral drug delivery system to improve the absorption of phillygenin. Full article

As a platform for hepsin-specific drug delivery, we previously prepared IPLVVPLRRRRRRRRC peptide (RIPL)-conjugated nanostructured lipid carriers (RIPL-NLCs) composed of Labrafil^® M 1944 CS (liquid oil) and Precirol^® ATO 5 (solid lipid). In this study, to prevent the recognition by the mononuclear phagocyte system, polyethylene glycol (PEG)-modified RIPL-NLCs (PEG-RIPL-NLCs) were prepared using PEG3000 at different grafting ratios (1, 5, and 10 mole %). All prepared NLCs showed a homogeneous dispersion (130–280 nm), with zeta potentials varying from −18 to 10 mV. Docetaxel (DTX) was successfully encapsulated in NLCs: encapsulation efficiency (93–95%); drug-loading capacity (102–109 µg/mg). PEG-RIPL-NLCs with a grafting ratio of 5% PEG or higher showed significantly reduced protein adsorption and macrophage phagocytosis. The uptake of PEG(5%)-RIPL-NLCs by cancer cell lines was somewhat lower than that of RIPL-NLCs because of the PEG-induced steric hindrance; however, the uptake level of PEG-RIPL-NLCs was still greater than that of plain NLCs. In vivo biodistribution was evaluated after tail vein injection of NLCs to normal mice. Compared to RIPL-NLCs, PEG(5%)-RIPL-NLCs showed lower accumulation in the liver, spleen, and lung. In conclusion, we found that PEG(5%)-RIPL-NLCs could be a promising nanocarrier for selective drug targeting with a high payload of poorly water-soluble drugs. Full article

In this study, an oral drug nanocrystals self-stabilized Pickering emulsion (NSSPE), which used nanocrystals of a poorly soluble ingredient from Puerariae Radix called puerarin as solid particle stabilizers and Ligusticum chuanxiong essential oil since the main oil phase had been developed to improve the oral bioavailability of puerarin. The appearance of emulsions, size and zeta potential of droplets, and content of puerarin in emulsified layer during a storage of six months at 4, 25, and 40 °C were investigated. The centrifugation stability at 4000× g was also studied. The micro-structure of emulsion droplets was characterized by a scanning electron micrograph (SEM), confocal laser scanning microscopy (CLSM), a fluorescence microscope (FM), and differential scanning calorimetry (DSC). The in vivo oral bioavailability of puerarin NSSPE was investigated in rats. Results showed that appearances of puerarin NSSPE kept stable after centrifugation at 4000× g for 15 min or storage for six months at 4, 25, and 40 °C. SEM, CLSM, FM, and DSC showed that the puerarin NSSPE had a stable core-shell structure of emulsion droplets formed by the adsorption of puerarin nanocrystals on the surface of oil droplets of mixed oil of Ligusticum chuanxiong essential oil and Labrafil M 1944 CS (9:1, v/v). The relative bioavailability of puerarin NSSPE to puerarin coarse powder suspension, nanocrystal suspension, and surfactant emulsion were 262.43%, 155.92%, and 223.65%, respectively. All these results indicated that puerarin nanocrystals could stabilize Pickering emulsion of Ligusticum chuanxiong essential oil without any other stabilizers and Pickering emulsion could improve the oral bioavailability of puerarin, which suggests that the drug nanocrystal self-stabilized Pickering emulsion as a promising oral drug delivery system for Traditional Chinese Medicine containing poorly soluble ingredients and volatile oils. Full article