Self-nanoemulsifying Drug Delivery System Formulation Research Articles

DISSOLUTION ENHANCEMENT OF TETRAHYDROCURCUMIN USING OPTIMIZED SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEM

Objective: The objective of this study was to optimize and enhance the dissolution of tetrahydrocurcumin (THC) using optimized self-nanoemulsifyingdrug delivery system (SNEDDS).Methods: The optimization was carried out with the D-optimal design using software design expert 7.15. The independent variables were the amountof oil, surfactant, and cosurfactant. The dependent variables were the emulsification time, percentage transmittance, and dissolution efficiency atminute 15 (DE15). The dissolution profile of the THC in optimum formulation compared with the unmodified THC.Results: The optimum formulation of SNEDDS consists of 10% Labrafil, 80% Kolliphor:Labrasol (1:3), and 10% PEG 400. The DE15 was 49.45%,significantly higher than the THC unmodified (p<0.05). The estimated responses were not significantly different from the experimental responses.The droplet size of the optimum formula was 53.8 nm, the polydispersity index was 0.043 and the zeta value was -19.4 mV.Conclusion: The D-optimal design was successfully determining the optimum formula of THC loaded SNEDDS. The SNEDDS formulation wasincreased the dissolution of THC.

A novel self-nanoemulsifying drug delivery system for curcumin used in the treatment of wound healing and inflammation.

The main objective of this study was to develop and evaluate self-nanoemulsifying drug delivery system (SNEDDS) of curcumin (Cur) to enhance their solubility as well as improve skin permeation; and evaluate wound healing potential of Cur via SNEDDS in comparison with standards pure eucalyptus oil-SNEDDS (Euc-SNEDDS), pure curcumin suspension (Cur-S), and standard fusidic acid followed by their anti-inflammatory action. Curcumin-loaded different SNEDDS formulations were formulated through aqueous phase titration method and the zones of SNEDDS were recognized by the construction of phase diagrams. Eucalyptus oil, Tween 80 (surfactant), and Transcutol HP (co-surfactant) were selected on the basis of their solubility and highest nanoemulsion region. Characterization of thermodynamic stability for Cur-loaded SNEDDS was evaluated by its globule size, zeta potential, polydispersity index, viscosity, % transmittance, refractive index, and surface morphology. Cur-SNEDDS (Cur-SN4) was optimized and selected on the basis of their excellent physicochemical parameters for in vivo activity. The particle size (59.56 ± 0.94nm), % transmittance (99.08 ± 0.07%), and PDI (0.207 ± 0.011 were observed for optimized Cur-SNEDDS. TEM and SEM showed their smooth and spherical shape of the morphological characterization with zeta potential (- 21.41 ± 0.89), refractive index (1.341 ± 0.06), and viscosity (11.64 ± 1.26 cp) for optimized Cur-SNEDDS. Finally, optimized Cur-SNEDDS was used to enhance skin permeation with improvement in the solubility of Cur. However, optimized Cur-SNEDDS showed significant wound healing activity as compared with pure eucalyptus oil and Cur-S on topical application. Optimized Cur-SNEDDS showed healing of wound as compared to standard fusidic acid. Optimized Cur-SNEDDS exhibited no signs of inflammatory cells on the histopathological studies of treated rats which were recommended the safety and non-toxicity of Cur-SNEDDS. Newly developed Cur-SNEDDS could be successfully used to enhance Cur-solubility and skin permeation, as well as suggested a potential role of Cur-SNEDDS for better improvement of wound healing activity followed by anti-inflammatory action of Cur via topical application.

Self-nanoemulsifying drug delivery system of fisetin: Formulation, optimization, characterization and cytotoxicity assessment

Fisetin is a plant derived flavonoid that possesses anti-cancer, anti-oxidant and anti-Parkinson's activities. However, due to its lipophilicity it suffers from dissolution rate limited oral bioavailability that reduces its therapeutic efficacy. In order to overcome this issue self-nanoemulsifying drug delivery system (SNEDDS) of fisetin were formulated and characterized for droplet size, shape, zeta potential, cell viability, dissolution and permeability studies. Prepared SNEDDS (1.2 mL) were composed of castor oil (0.1 mL), Lauroglycol FCC (0.1 mL), tween 80 (0.4 mL), Transcutol P (0.6 mL) and fisetin (5 mg). The formulation was optimized using Box Behnken Design. Droplet size and zeta potential of optimized SNEDDS were found to be 154 nm and −37 mV. Dissolution rate of fisetin got significantly (p < 0.05) enhanced through SNEDDS formulation in all the media as compared to unprocessed fisetin. Toxicity studies revealed more cell viability (89.05%) for fisetin loaded in SNEDDS as compared to its unprocessed form (10.8%) at a fixed concentration (62.5 μg/mL). The in-vitro cell line study revealed about 3.79 folds increase in permeation rate for fisetin loaded in SNEDDS. The developed formulation was found to be stable with change in temperature, dilution and pH. The study entailed successful formulation of SNEDDS loaded with fisetin.

Solidification of meloxicam self-nano emulsifying drug delivery system formulation incorporated into soluble and insoluble carriers using freeze drying method

Solidification of liquid self-nano emulsifying drug delivery system (SNEDDS) formulation is required to enhance the feasibility and flexibility for further formulation processes. This study purposed to compare the soluble and insoluble carriers namely mannitol and fumed silica, respectively on the nano-emulsion formation and physical properties. The optimized SNEDDS formulation comprising of virgin olive oil, Tween 80, and PEG 400; and meloxicam was impregnated into solid carriers e.g. mannitol and fumed silica using a freeze-drying method. The physical mixture was carried out to compare the aforementioned method. Vibrational spectroscopy, thermal analysis, and morphological characteristic, droplet size and distribution, and drug release were performed to characterize the solid SNEDDS (S-SNEDDS). The result showed that crystallization of meloxicam did not observe in the S-SNEDDS formulations, which confirmed by the vibrational spectroscopy and thermal analysis. The morphological characteristic of S-SNEDDS was similar to the native carriers. The soluble carrier did not affect the formation of the nano-emulsion compared to the insoluble carrier. In addition, the S-SNEDDS enhanced the drug release of meloxicam up to 3-4 folds increment.

Optimization of Self-Nanoemulsifying Drug Delivery System (SNEDDS) of Annona muricata L. leaves chloroform extract using VCO (Virgin Coconut Oil) as an oil phase

Annona muricata L. also called as soursop is one of medicinal plants that have a broad spectrum of biological activities and the most impressive of which is anticancer activity. Annonaceous acetogenins (ACGs) have been shown to successfully induce death in cancer cell. However, the solubility of ACGs is poor, so modification of formula of Self-Nanoemulsifying Drug Delivery System (SNEDDS) can be used for improving drug solubility. This study was used Annona muricata L. leaf chloroform extract then optimized to formula of SNEDDS using D-Optimal mixture design (Design Expert 9 Trial software). Sixteen formulas from the software consisting of oil phase (VCO), surfactant (tween 80-cremophor EL), and co-surfactant (propylene glycol) were tested of loading dose extract and characterized for transmittance, emulsification time, and phase separation. One sample t-test was used for verification, then the optimum SNEDDS was evaluated against particle size, polidispersity index, zeta potential, and TLC test was used to predict the active ingredient in the extract. The optimum SNEDDS consisting of 22.00% oil : 60.79% surfactant : 17.21% co-surfactant showed desirability value 0.608 and can loaded 25 mg/g extract. The optimum SNEDDS showed 84.4% (SE ± 1.64) of transmittance; 14.79 seconds (SE ± 1.81) of emulsification time; and 0.898 (SE ± 0.01) of phase separation. The verification test showed no significant difference (p >0.05) between the observation and the prediction from the software. Evaluation results showed 42.73 nm (SE ± 0.49) of the particle size; polidispersity index 0.37 (SE ± 0.10); -27.43 mV (SE ± 0.26) of zeta potential, and TLC results showed similarity of active ingredient in the extract with the active compound of the fraction. Therefore, from these results suggest that the optimum SNEDDS achieved the nanoparticle size for SNEDDS formulation and may be improving drug solubility.

A Self-Nanoemulsifying Drug Delivery System for Enhancing the Oral Bioavailability of Candesartan Cilexetil: Ex Vivo and In Vivo Evaluation

The drug delivery of candesartan cilexetil encounters an obstacle of low absolute oral bioavailability which is attributed mainly to its low aqueous solubility and efflux by intestinal P-glycoprotein (P-gp) transporters. However, the extent of P-gp contribution in the reduced oral bioavailability of candesartan cilexetil is not clear. In this study, a previously developed candesartan cilexetil–loaded self-nanoemulsifying drug delivery system (SNEDDS) was evaluated for its ability to increase the drug oral bioavailability via the inhibition of intestinal P-gp transporters. Despite the developed SNEDDS showing P-gp inhibition activity, P-gp–mediated efflux was found to have a minor role in the reduced oral bioavailability of candesartan cilexetil. On the other hand, the high surfactant concentration used in SNEDDS formulation represents a major challenge toward their widespread application especially for chronically administered drugs. The designed acute and subacute toxicity studies revealed that the degree of intestinal mucosal damage decreases as the treatment period increases. The latter observation was attributed to the reversibility of surfactant-induced mucosal damage. Thus, the developed SNEDDS could be considered as a promising delivery system for enhancing the oral bioavailability of chronically administered drugs.

Preparation and Characterization of Self Nano-Emulsifying Drug Delivery System Loaded with Citraland Its Antiproliferative Effect on Colorectal Cells In Vitro.

Citral is an active compound naturally found in lemongrass, lemon, and lime. Although this pale-yellow liquid confers low water solubility, the compound has been reported to possess good therapeutic features including antiproliferative and anticancer modalities. The self nano-emulsifying drug delivery system (SNEDDS) is a type of liquid-lipid nanocarrier that is suitable for the loading of insolubilized oil-based compound such as Citral. This study reports the design and optimization of a SNEDDS formulation, synthesis and characterization as well as loading with Citral (CIT-SNEDDS). Further assessment of theantiproliferative effects of CIT-SNEDDS towards colorectal cancer cells was also conducted. SNEDDS composed of coconut oil, dimethyl sulfoxide (DMSO) and Tween 80. CIT-SNEDDS was prepared via gentle agitation of SNEDDS with 0.5% Citral for 72 h at room temperature. Physicochemical characterization was performed using several physicochemical analyses. The average particle size of CIT-SNEDDS was16.86 ± 0.15 nm, zeta potential of 0.58 ± 0.19 mV, and polydispersity index (PDI) of 0.23 ± 0.01. In vitro drug release of Citral from CIT-SNEDDS was 79.25% of release, and for Citral the release percentage was 93.56% over 72 h. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was done to determine the cytotoxicity effect of CIT-SNEDDS in human colorectal cancer cell lines HT29 and SW620. The half maximal inhibitory concentrations (IC50) for 72 hof CIT-SNEDDS and Citral on SW620 were 16.50 ± 0.87 µg/mL and 22.50 ± 2.50 µg/mL, respectively. The IC50 values of CIT-SNEDDS and Citral after 72 h of treatment on HT29 were 34.10 ± 0.30 µg/mL and 21.77 ± 0.23 µg/mL, respectively. This study strongly suggests that CIT-SNEDDS has permitted the sustained release of Citral and that CIT-SNEDDS constitutes a potential soluble drug nanocarrier that is effective against colorectal cancer cells.

Novel oral dosage regimen based on self-nanoemulsifying drug delivery systems for codelivery of phytochemicals – Curcumin and thymoquinone

BackgroundCurcumin and Thymoquinone are very well-known phytochemicals for their potent anti-inflammatory and anticancer properties. The major challenges for curcumin is its poor aqueous solubility and erratic oral bioavailability. ObjectiveTo develop a novel liquid self-nanoemulsifying drug delivery system (SNEDDS) containing curcumin and thymoquinone and further converted into a solid dosage form using adsorbents Syloid® and Neusilin® as the solid carrier. MethodsThe characterization of the liquid and solid SNEDDS was performed by particle size & zeta potential analysis, scanning electron microscopy, differential scanning calorimetry, fourier transform infrared spectroscopy and X-ray powder diffraction. The drug loading, and in vitro release studies were carried out to investigate the efficiency of curcumin release from SNEDDS. ResultsThe liquid SNEDDS containing black seed oil showed excellent self-emulsification performance with transparent appearance. The results of characterization studies showed that solidification using 50% (w/w) Syloid® and Neusilin® in the liquid formulation yield free flowing powder with no agglomeration but Neusilin® produced smooth granules than Syloid® and kept the drugs stable in amorphous state. In vitro dissolution studies indicated that liquid SNEDDS formulations of F4 and its solid SNEDDS using Neusilin® provided high dissolution efficiency and reproducibility for curcumin and thymoquinone. However, Neusilin® showed higher rate of dissolution (more than 65%, p < 0.05) compared to Syloid® for curcumin. ConclusionsCurcumin loaded-SNEDDS formulation containing thymoquinone in liquid & solid dosage forms were successfully developed with an increased drug loading and dissolution rate, which could be the potential combined delivery system for various anti-inflammatory and anti-cancer treatments.

Self-Nanoemulsifying Drug Delivery System (SNEDDS) for Improved Oral Bioavailability of Chlorpromazine: In Vitro and In Vivo Evaluation.

Background and Objectives: Lipid-based self-nanoemulsifying drug delivery systems (SNEDDS) have resurged the eminence of nanoemulsions by modest adjustments and offer many valuable opportunities in drug delivery. Chlorpromazine, an antipsychotic agent with poor aqueous solubility—with extensive first-pass metabolism—can be a suitable candidate for the development of SNEDDS. The current study was designed to develop triglyceride-based SNEDDS of chlorpromazine to achieve improved solubility, stability, and oral bioavailability. Materials and Methods: Fifteen SNEDDS formulations of each short, medium, and long chain, triglycerides were synthesized and characterized to achieve optimized formulation. The optimized formulation was characterized for several in vitro and in vivo parameters. Results: Particle size, zeta potential, and drug loading of the optimized SNEDDS (LCT14) were found to be 178 ± 16, −21.4, and 85.5%, respectively. Long chain triglyceride (LCT14) showed a 1.5-fold increased elimination half-life (p < 0.01), up to 6-fold increased oral bioavailability, and 1.7-fold decreased plasma clearance rate (p < 0.01) compared to a drug suspension. Conclusion: The findings suggest that SNEDDS based on long-chain triglycerides (LCT14) formulations seem to be a promising alternative for improving the oral bioavailability of chlorpromazine.

Evaluation of Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) for Poorly Water-Soluble Talinolol: Preparation, in vitro and in vivo Assessment.

ObjectiveThe aim of this study was to investigate the in vitro and in vivo performance of self-nanoemulsifying drug delivery systems (SNEDDSs) of talinolol (TAL), a poorly water-soluble drug.MethodsSelf-nanoemulsifying drug delivery systems of TAL were prepared using various oils, non-ionic surfactants and/or water-soluble co-solvents and assessed visually/by droplet size measurement. Equilibrium solubility of TAL in the anhydrous and diluted SNEDDS was conducted to achieve the maximum drug loading. The in vitro dissolution experiments and human red blood cells (RBCs) toxicity test, ex vivo gut permeation studies, and bioavailability of SNEDDS in rats were studied to compare the representative formulations with marketed product Cordanum® 50 mg and raw drug.ResultsThe results from the characterization and solubility studies showed that SNEDDS formulations were stable with lower droplet sizes and higher TAL solubility. From the dissolution studies, it was found that the developed SNEDDS provided significantly higher rate of TAL release (>97% in 2.0 h) compared to raw TAL and marketed product Cordanum®. The RBC lysis test suggested negligible toxicity of the formulation to the cells. The ex vivo permeability assessment and in vivo pharmacokinetics study of a selected SNEDDS formulation (F6) showed about four-fold increase in permeability and 1.58-fold enhanced oral bioavailability of TAL in comparison to pure drug, respectively.ConclusionTalinolol loaded SNEDDS formulations could be a potential oral pharmaceutical product with high drug-loading capacity, improved drug dissolution, increased gut permeation, reduced/no human RBC toxicity, and enhanced oral bioavailability.

Formulation and characterisation of a self‐nanoemulsifying drug delivery system of amphotericin B for the treatment of leishmaniasis

This study was aimed to develop a self‐nanoemulsifying drug delivery system (SNEDDS) for amphotericin B (AmB) potential use in leishmaniasis through topical and oral routes. Two formulations, formulation A and formulation B (FA and FB) of AmB loaded SNEDDS were developed by mixing their excipients through vortex and sonication. The SNEDDS formulation FA and FB displayed a mean droplet size of 27.70 ± 0.5 and 30.17 ± 0.7 nm and zeta potential −11.4 ± 3.25 and −13.6 ± 2.75 mV, respectively. The mucus permeation study showed that formulation FA and FB diffused 1.45 and 1.37%, respectively in up to 8 mm of mucus. The cell permeation across Caco‐2 cells monolayer was 10 and 11%, respectively. Viability of Caco‐2 cells was 89% for FA and 86.9% for FB. The anti‐leishmanial activities of FA in terms of IC50 were 0.017 µg/ml against promastigotes and 0.025 µg/ml against amastigotes, while IC50 values of FB were 0.031 and 0.056 µg/ml, respectively. FA and FB killed macrophage harboured Leishmania parasites in a dose‐dependent manner and a concentration of 0.1 µg/ml killed 100% of the parasites. These formulations have the potential to provide a promising tool for AmB use through oral and topical routes in leishmaniasis therapy.

Development and optimization of self-nanoemulsifying drug delivery systems (SNEDDS) for curcumin transdermal delivery: an anti-inflammatory exposure

The purpose of this work is to develop novel lipid-based self-nanoemulsifying drug delivery systems (SNEDDS) as carriers for transdermal delivery of curcumin. SNEDDS containing black seed oil, medium chain mono- and diglycerides and surfactants, were prepared as curcumin delivery vehicles. Their formation spontaneity, morphology, droplet size, and drug loading were evaluated. Gel preparation containing two of the SNEDDS formulations were used in the carrageenan induced paw edema to evaluate the anti-inflammatory effect. Results showed droplet size as low as 71 nm. The highest drug loading was observed with SNEDDS-F6 of ∼45 mg/g. In in-vivo investigation, SNEDDS-F6 exhibited significant anti-inflammatory activities in terms of 80% reduction in paw edema when compared with positive control. The prepared SNEDDS with the elevated entrapment efficiency, good transdermal penetration ability could be a suitable candidate for effective transdermal curcumin skin delivery.

Development and Characterization of a Self-Nanoemulsifying Drug Delivery System Comprised of Rice Bran Oil for Poorly Soluble Drugs.

Poor aqueous solubility and low bioavailability are limiting factors in the oral delivery of lipophilic drugs. In a formulation approach to overcome these limitations, rice bran (RB) oil was evaluated as drug carrier in the development of self-nanoemulsifying drug delivery systems (SNEDDS). The performance of RB in formulations incorporating Kolliphor RH40 or Kolliphor EL as surfactants and Transcutol HP as cosolvent was compared to a common oil vehicle, corn oil (CO). Serial dilutions of the preconcentrates were performed in various media [distilled water and simulated intestinal fluids mimicking fasted state (FaSSIF) and fed state (FeSSIF)] and at different dilution ratios to simulate the in vivo droplets' behavior. The developed SNEDDS were assessed by means of phase separation, droplet size, polydispersity index, and ζ-potential. Complex ternary diagrams were constructed to identify compositions exhibiting monophasic behavior, droplet size < 100nm, and polydispersity index (PDI) < 0.25. Multifactor analysis and response surface areas intended to determine the factors significantly affecting droplet size. The oil capacity to accommodate lipophilic drugs was assessed via fluorescence spectroscopy based on the solvatochromic behavior of Nile Red. Solubility studies were performed to prepare fenofibrate- and itraconazole-loaded SNEDDS and assess their droplet size, whereas dissolution experiments were conducted in simulated intestinal fluids. Caco-2 cell viability studies confirmed the safety of the SNEDDS formulations at 1:100 and 1:1000 dilutions after cell exposure in culture for 4h. The obtained results showed similar performance between RB and CO supporting the potential of RB as oil vehicle for the effective oral delivery of lipophilic compounds.

Taste Evaluation by Electronic Tongue and Bioavailability Enhancement of Efavirenz.

Self-nanoemulsifying drug delivery systems (SNEDDS) are isotropic and thermodynamically stable mixtures of oil, surfactant, co-surfactant, and drug which emulsify spontaneously on contact with aqueous phase under mild agitation. Efavirenz used for treatment of acquired immune deficiency syndrome, is poorly water soluble and bitter tasting drug resulting in "burning mouth syndrome (BMS)." The objective of this study was to improve solubility and oral bioavailability by formulating liquid-SNEDDS and to mask bitter taste and minimize BMS. Capmul PG8 NF, Cremophor RH40, and Transcutol HP were selected as oil, surfactant, and co-surfactant. Ternary phase diagrams were constructed to evaluate the nanoemulsification region. A 32 factorial design was employed to optimize L-SNEDDS with droplet size and drug release as responses. Optimized batch was subjected to evaluation of taste by human panel method and electronic tongue, cloud point determination, phase separation, in vivo and stability studies. The optimized batch exhibited droplet size of 21.53nm, polydispersibility index 0.155, and in vitro drug release of 92.26% in 60min. The in vivo studies revealed 4.5 times enhancement in oral bioavailability. Taste evaluation indicated reduced the intensity and shortened duration of BMS. The formulation was stable at 40°C ± 75% RH after 3months. Comparison between standard bitter drug and efavirenz in SNEDDS formulation using e-tongue by principal component analysis revealed significant differences in discrimination index, computed by multivariate data analysis. This study demonstrated that L-SNEDDS may be an alternative approach to improve solubility and oral bioavailability and for masking the bitterness of efavirenz.

Formulation and In-vitro Characterization of Self Nano-emulsifying Drug Delivery System (SNEDDS) for enhanced Solubility of Candesartan Cilexetil

Candesartan cilexetil is the prodrug of candesartan, a selective angiotensin II receptor antagonist, used in the management of hypertension and heart failure. It is characterized by poor aqueous solubility resulting in low bioavailability. Self-nanoemulsifying drug delivery systems (SNEDDS) loaded with candesartan cilexetil were successfully developed to overcome such obstacles. Preliminary screening was carried out to select proper oil, surfactant and co-surfactant combination for successful SNEDDS formulation. Ternary and pseudo ternary diagrams were constructed to optimize the system. Capryol 90® as an oil showed high emulsification ability. The nature of obtained dispersions was found to be nanoemulsions. Six formulations were visually inspected and evaluated for stability, robustness to dilution, effect of drug loading on the nano-emulsion boundary, viscosity, content uniformity, their mean droplet size, polydispersity index (PDI), zeta potential in addition to in vitro drug release study. Three formulations showed a very short emulsification time of less than 3minutes. The emulsification efficiency was significantly superior at pH6.8. All selected formulations showed mean droplet size (124.25 to 460.15nm), very low PDI values (0.311–0.562) and zeta potential (30.5–44.45 mV). Formulation F16 (10% w/w Capryol 90®, 30% w/w Tween80, 60% w/w Transcutol®) was selected for further characterization. Droplet size of F16 showed robustness to different dilution folds with different media. These results indicate that, SNEDDS could be promising delivery systems with a rapid onset of action and prolonged therapeutic effect of candesartan cilexetil.

Enhancement of zaleplon oral bioavailability using optimized self-nano emulsifying drug delivery systems and its effect on sleep quality among a sample of psychiatric patients

The aim of this work is to develop self-nano emulsifying drug delivery system (SNEDDS) to enhance the oral bioavailability of zaleplon (Zal) as a poorly water-soluble drug. Moreover, the bioavailability and the effect on the quality of sleep among a sample of psychiatric patients is to be assessed. D-optimal mixture design was used for optimization. Optimized SNEDDS formulation was evaluated for droplet size, transmission electron microscope (TEM) and in-vitro dissolution test. Zal bioavailability was evaluated by determining its serum concentration and pharmacokinetic parameters in 8 patients after oral administration. Effect on sleep quality was assessed among 40 psychiatric patients. Patients’ sleep quality was assessed in 40 psychiatric patients before and after medication using the Arabic version of the Pittsburgh Sleep Quality Index (PSQI). Zal- SNEDDS appeared as nano-sized spherical vesicles. Moreover, Zal was completely dissolved from optimized formulation after 45 min indicating improved dissolution rate. Zal-SNEDDS showed significantly higher Cmax, Tmax and AUC0→∞ compared to commercial product after oral administration. Zal-SNEDDS significantly improved the total score of PSQIs (p < .001) with higher subjective sleep quality, reduced sleep latency, improved day time function and sleep disturbance (p < .001). Using sleep medication was reduced significantly (p = .027). However, it did not modify sleep duration or sleep efficiency. SNEDDS have improved Zal solubility and enhanced its bioavailability. Furthermore, Zal-SNEDDS have improved the total score of PSQIs and may be considered a good choice to enhance the quality of sleep among psychiatric patients.

Evaluation of a self-nanoemulsifying docetaxel delivery system

A self-nanoemulsifying drug delivery system (SNEDDS) was developed as a novel route to enhance the efficacy of docetaxel lipophilic drug. SNEDDS comprised ethyl oleate, Tween 80 and poly(ethylene glycol) 600, as oil, surfactant and co-surfactant, and formed stabilized monodispersed oil nanodroplets upon dilution in water. SNEDDS represented encapsulation efficiency and loading capacity of 21.4 and 52.7%, respectively. The docetaxel release profile from the drug-loaded SNEDDS was recorded, its effectiveness against MCF-7 cell line was investigated, and an IC50 value of 0.98 ± 0.05 μg mL−1 was attained. The drug-loaded SNEDDS was administrated in rats, and the pharmacokinetic parameters of maximum concentration of 22.2 ± 0.8 μg mL-1, time to attain this maximum concentration of 230 min, and area under the curve of 1.71 ± 0.18 μg min mL-1 were obtained. The developed SNEDDS formulation can be represented as an alternative to docetaxel administration.

Formulation development of self-nanoemulsifying drug delivery system of celecoxib for the management of oral cavity inflammation

The oral administration of celecoxib (CLX) is a real problem because of its low aqueous solubility that results in high variability in absorption and its severe adverse effect such as cardiotoxic effects and gastrointestinal toxicity. Self-nanoemulsifying drug delivery systems (SNEDDS) can enhance the poor dissolution and erratic absorption of poorly water-soluble drugs such as CLX. This study was conducted to investigate the potential of SNEDDS to enhance the efficacy of CLX on inflamed mucous tissue and reduce systemic adverse effects by increasing its poor dissolution properties. A pseudo-ternary phase diagram was derived from the results of CLX solubility experiments in various excipients. These studies revealed the use of Labrafil M 2515 CS as oil, tween 80 as a surfactant, and polyethylene glycol 400 as a co-surfactant for the optimization of SNEDDS formulations. Eight formulations were formulated and characterized by their particle size, polydispersity index, viscosity, globular shape, drug solubility, self-emulsification efficiency, in vitro drug release, and permeation. The anti-inflammatory effect of CLX-SNEDDS was evaluated by carrageenan-induced cheek oedema in rats. The cheeks were treated with CLX-SNEDDS before oedema induction and then noticed for narrow periods (2 h) followed by histopathological studies to determine the efficacy of treatment. The selected formulations (F3 and F5) showed spherical morphologies under transmission electron microscopy, mean droplet sizes of 116.9 ± 1.78 and 124 ± 1.87 nm, respectively, complete in vitro drug release, and high cumulative amounts of drug permeation in 8 h. They also showed significant remarkable cheek oedema inhibition in comparison with the control groups (p < 0.05). CLX-SNEDDS was found to achieve effective local therapeutic concentration and intended to reduce cheek oedema, congestive capillary, inflammatory cells, and side effects due to lower dose size.

Integration of phospholipid-drug complex into self-nanoemulsifying drug delivery system to facilitate oral delivery of paclitaxel

Self-nanoemulsifying drug delivery system (SNEDDS) has emerged as a promising platform to improve oral absorption of drugs with poor solubility and low permeability. However, large polarity molecules with insufficient lipid solubility, such as paclitaxel (PTX), would suffer from inferior formulation of SNEDDS due to poor compatibility. Herein, phospholipid-drug complex (PLDC) and SNEDDS were integrated into one system to facilitate oral delivery of PTX. First, PTX was formulated into PLDC in response to its inferior physicochemical properties. Then, the prepared PLDC was further formulated into SNEDDS by integrating these two drug delivery technologies into one system (PLDC-SNEDDS). After PLDC-SNEDDS dispersed in aqueous medium, nanoemulsion was formed immediately with an average particle size of ∼30 nm. Furthermore, the nanomulsion of PLDC-SNEDDS showed good colloidal stability in both HCl solution (0.1 mol/l, pH 1.0) and phosphate buffer solution (PBS, pH 6.8). In vivo, PTX-PLDC-SNEDDS showed distinct advantages in terms of oral absorption efficiency, with a 3.42-fold and 2.13-fold higher bioavailability than PTX-PLDC and PTX solution, respectively. Our results suggest that the integration of PLDC into SNEDDS could be utilized to facilitate the oral delivery of hydrophobic drugs with large polarity.

Role of Alternative Lipid Excipients in the Design of Self-Nanoemulsifying Formulations for Fenofibrate: Characterization, in vitro Dispersion, Digestion and ex vivo Gut Permeation Studies.

Background: The choice of lipid excipients and their origin are crucial determinant factors in the design of self-nanoemulsifying drug delivery system (SNEDDS).Aim: To investigate the aspects of alternative excipients which can influence the development of efficient SNEDDS and determine the fate of fenofibrate in aqueous media.Methods: SNEDDS of two groups (a and b) were developed using Cremercoor MCT/Capmul MCM and Kollisolv MCT/Imwitor 742 blended oils and water soluble surfactants (to improve lipid polarity) for the model anti-cholesterol drug fenofibrate. Visual assessment was employed and droplet size measurement was taken into initial consideration for optimized SNEDDS. Further SNEDDS optimizations were done on the basis of maximum drug loading by equilibrium solubility studies and maximum solubilized drug upon aqueous dispersion by dynamic dispersion studies. In vitro lipolysis was examined under simulated Fed and Fasted conditions. Intestinal permeability study of the optimal SNEDDS formulation was compared with the raw fenofibrate dispersion using non- everted “intestinal sac technique.”Results: Initial characterization and solubility studies showed that mixed glycerides of Kollisolv MCT/Imwitor 742 (group b) containing formulations generated highly efficient SNEDDS as they are stable and produced lower nanodroplets with higher drug loading (group b) as compared to mixed glycerides of Cremercoor MCT/Capmul MCM (group a). In vitro dispersion and digestion studies confirmed that SNEDDS of group b (polar mixed glycerides) can retain high amount of drug (99% drug in solution for more than 24 h time) in dispersion media and have high recovery after digestion. The results from the permeability assessment confirmed that fenofibrate had 4.3-fold increase with F3b SNEDDS compared with the control.Conclusion: SNEDDS formulations containing alternative excipients (Kollisolv MCT/Imwitor 742 blend) could be a potential oral pharmaceutical product in taking anti-hyperlipidaemic agent fenofibrate to the systemic circulation as solubilized form.