Self-nanoemulsifying System Research Articles

Paclitaxel-loaded TPGS enriched self-emulsifying carrier causes apoptosis by modulating survivin expression and inhibits tumour growth in syngeneic mammary tumours

Paclitaxel (PTX) in its commercial products exhibits adverse effects owing to excipients and also has poor oral bioavailability. Present work is directed towards development of tocopheryl polyethylene glycol succinate-assisted self-nanoemulsifying system (SEDDS) for oral delivery of PTX. Box–Behnken design of experiment was employed to optimize PTX-SEDDS and was characterized for droplet size (29.76 ± 2.64 nm), zeta potential (–21.46 ± 2.52 mV), PDI (0.177 ± 0.012), drug content (4.97 ± 0.98 mg), entrapment efficiency (98.33 ± 0.54%) and in vitro drug release (51.03 ± 2.23% PTX at 72 h). PTX-SEDDS exhibited IC50; 1.58 ± 0.12 µM and a 52.46-folds higher cell uptake in MDA-MB-231 cells along with cellular and nuclear morphology changes. Significantly higher G2M cell cycle arrest, apoptosis, mitochondrial membrane potential disruption and ROS production was exhibited by PTX-SEDDS in comparison to Taxol. Up-regulation of Bax, p21, cleaved-caspase 3, -caspase 9 and down-regulation of Bcl2 and survivin suggested apoptosis via intrinsic pathways. Pharmacokinetic study showed approximately 4-folds higher oral bioavailability of PTX-SEDDS than Taxol. Significant reduction in tumour volume and weight was observed in syngeneic mammary tumour in SD rats. Tumour histopathology and TUNEL assay showed apoptosis in tumour tissue. PTX-SEDDS caused low lung metastasis, and was safe and stable. Conclusively, PTX-SEDDS could be suitable option for oral delivery of PTX.

Orally Bioavailable and Effective Buparvaquone Lipid-Based Nanomedicines for Visceral Leishmaniasis.

Nanoenabled lipid-based drug delivery systems offer a platform to overcome challenges encountered with current failed leads in the treatment of parasitic and infectious diseases. When prepared with FDA or EMA approved excipients, they can be readily translated without the need for further toxicological studies, while they remain affordable and amenable to scale-up. Buparvaquone (BPQ), a hydroxynapthoquinone with in vitro activity in the nanomolar range, failed to clinically translate as a viable treatment for visceral leishmaniasis due to its poor oral bioavailability limited by its poor aqueous solubility (BCS Class II drug). Here we describe a self-nanoemulsifying system (SNEDDS) with high loading and thermal stability up to 6 months in tropical conditions and the ability to enhance the solubilization capacity of BPQ in gastrointestinal media as demonstrated by flow-through cell and dynamic in vitro lipolysis studies. BPQ SNEDDS demonstrated an enhanced oral bioavailability compared to aqueous BPQ dispersions (probe-sonicated), resulting in an increased plasma AUC0-24 by 55% that is 4-fold higher than any previous reported values for BPQ formulations. BPQ SNEDDS can be adsorbed on low molecular glycol chitosan polymers forming solid dispersions that when compressed into tablets allow the complete dissolution of BPQ in gastrointestinal media. BPQ SNEDDS and BPQ solid SNEDDS demonstrated potent in vitro efficacy in the nanomolar range (<37 nM) and were able to near completely inhibit parasite replication in the spleen while also demonstrating 48 ± 48 and 56 ± 23% inhibition of the parasite replication in the liver, respectively, compared to oral miltefosine after daily administration over 10 days. The proposed platform technology can be used to elicit a range of cost-effective and orally bioavailable noninvasive formulations for a range of antiparasitic and infectious disease drugs that are needed for closing the global health innovation gap.

Development of a fluvastatin-loaded self-nanoemulsifying system to maximize therapeutic efficacy in human colorectal carcinoma cells

Self-nanoemulsifying delivery systems (SNEDs) are one of the most important approaches for increasing the solubilization and absorption of a drug. This study aimed to develop a system using fluvastatin (FLV) in SNEDs with minimum globule size to enhance cellular uptake and induce apoptosis in human colorectal cancer cells (HCT-116). Thirteen formulations of FLV-loaded SNEDs were prepared, analyzed, and optimized with the extreme vertices mixture design. The optimized formulation had globules 88.4 nm in size, and an IC50 of 23.38 ± 4.2 μM compared to 52.69 ± 6.6 μM for the raw drug. This optimized formulation was evaluated in HCT-116 cells for its cellular uptake, in vitro cytotoxicity, and the induction of apoptosis. The cellular uptake efficiency of FLV-loaded SNEDs was 47.9 ± 5.6% and 71.7 ± 10.2% after 2 and 4 h incubation times, respectively, which represents a three-fold increase over the raw drug efficiency. Cellular morphology and DNA fragments confirmed potentiation of apoptosis. These results indicate that loading FLV in SNEDs improves its cellular uptake and hence increases cytotoxicity, making this a promising approach for the treatment of patients with colorectal carcinoma.

Simultaneous determination of Curcumin (Cur) and Thymoquinone (THQ) in lipid based self-nanoemulsifying systems and its application to the commercial product using UHPLC-UV-Vis spectrophotometer

Simultaneous determination of Curcumin (Cur) and Thymoquinone (THQ) in lipid based self-nanoemulsifying systems and its application to the commercial product using UHPLC-UV-Vis spectrophotometer

Enhanced digestion inhibition and mucus penetration of F127-modified self-nanoemulsions for improved oral delivery

Self-nanoemulsifying systems (SNEs) have excellent ability to improve the solubility of poorly water-soluble drugs (PWSD). However, SNEs are likely to be degraded in gastrointestinal (GIT) when their surface is recognized by lipase/co-lipase enzyme complex, resulting in rapid release and precipitation of encapsulated drugs. The precipitates are then captured and removed by intestinal mucus, reducing the delivery efficacy of SNEs. Herein, the amphiphilic polymer Pluronic® F127 was incorporated into long and short-chain triglycerides (LCT, SCT) based SNEs to diminish the recognition and therefore minimized their degradation by enzymes and clearance by mucus. The SNEs were characterized in terms of particle size, zeta potential and stability. Ex vivo multiple particles tracking studies were performed by adding particle solution into fresh rat mucus. Cellular uptake of SNEs were conducted by using E12 cells, the absorption and distribution in small intestine were also studied after oral administration in male Sprague-Dawley (SD) rats. The in vitro digestion rate of SNEs were found to be in following order SCT-SNE > SCT-F127-SNE > LCT-SNE > LCT-F127-SNE. Moreover, the LCT-F127-SNE was found to be most effective in enhancing cellular uptake, resulting in 3.5-fold, 2.1-fold and 1.7-fold higher than that of SCT-SNE, LCT-SNE and SCT-F127-SNE, respectively. After incubating the SNE with E12 cells, the LCT-F127-SNE exhibited the highest amount regarding both mucus penetration and cellular uptake, with an uptake amount number (via bicinchoninic acid (BCA) analysis) of 3.5-fold, 2.1-fold and 1.7-fold higher than that of SCT-SNE, LCT-SNE and SCT-F127-SNE, respectively. The in vivo results revealed that orally administered LCT-F127-SNE could significantly increase the bioavailability of Cyclosporine A (CsA), which was approximately 2.43-fold, 1.33-fold and 1.80-fold higher than that of SCT-SNE, SCT-F127-SNE and LCT-SNE, respectively. We address in this work that F127-modified SNEs have potentials to improve oral drug absorption by significantly reducing gastrointestinal enzymatic degradation and simultaneously enhancing mucus penetration.

Development and investigation of novel solid self-nanoemulsifying system loaded with hydrochlorothiazide for the treatment of hypertension

Objective: The present study was aimed at formulating and evaluating a novel solid self‑nano emulsifying drug delivery system (SNEDDS) to increase the solubility and bioavailability of hydrochlorothiazide (HCZ). Enhancing both solubility and bioavailability of drugs remain the cornerstone for achieving successful outcomes of delivery systems. Furthermore, employing nanotechnology‑based formulations such as SNEDDS offers important advantage; the most important is the protection of the drug from enzymatic or chemical degradation. Materials and Methods: Liquid SNEDDS (L‑SNEDDS) was prepared by adding a drug to oil, surfactant, and co‑surfactant and heated up to at 60°C under continuous stirring. Solid SNEDDS (S‑SNEDDS) was prepared by mixing L‑SNEDDS with microcrystalline cellulose in 1:1 proportion. Results: The scanning electron microscopy showed that S‑SNEDDS was spherical with an average particle size of 66.9 nm and 69.2 nm for both L‑SNEDDS and S‑SNEDDS, respectively. Ex vivo skin permeation study indicated that 100% drug was released from both the L‑SNEDDS and S‑SNEDDS formulation SF3 in 3 h. Analysis of variance test showed significant differences (Moderately significant P < 0.01) in the values when compared to a marketed product. Conclusion: The prepared S‑SNEDDS helped in improving the solubility of the poorly soluble HCZ, which is a step forward toward bioavailability enhancement and thus increased therapeutic efficacy of the drug.

In vitro characterization of statistically optimized quetiapine-loaded self-nanoemulsified systems with quality by design

Objective: To optimize and characterize quetiapine (QP)-loaded self-nanoemulsified drug delivery systems (SNEDDS) by 3-factorial 3-level Box–Behnken design (BBD) to improve the dissolution. Methods: Amounts of olive oil (X 1 ), tween 80 (X 2 ), and PEG 400 (X 3 ) as independent factors, whereas % limpidity (Y1), self-emulsification time (SET) (Y2), and drug released at 15 min (T 15 ) (Y3) as responses were employed in BBD. Three-dimensional response surface plots were run to understand the main interaction and quadratic effects of independent variables. Preliminary screening was carried out by equilibrium solubility and emulsification efficiency studies. Nanoemulsification region was recognized by pseudoternary plot. Results: Mean droplet size of optimized nanodispersion was 89.68 nm, electrokinetic potential was −27.2 mV and polydispersity index 15 . Software-generated model graphs (predicted versus actual and residual versus predicted) for all three responses were produced without outliers and thus indicated the adequacy of selected statistical model. Conclusion: This study explained the effectiveness of BBD in insights of formulation variables and quality of QP-loaded nanoemulsified systems so as to enhance dissolution. As a result, BBD was a well-suitable experimental design in predicting the responses of QP-loaded liquid SNEDDS.

Self-nanoemulsifying system (SNES) enhanced oral bioavailability of boswellic acids

Boswellia serrate gum resin extract is a potent anti-inflammatory agent that is widely used in ancient and modern medicinal systems. However, the efficacy of this bioactive ingredient is questionable due to its poor oral bioavailability. In this work, self-nanoemulsifying system (SNES) was used to enhance the systemic concentration of boswellic acids. The systemic concentrations of 11-keto-β-boswellic acid (KBA) and acetyl-11-keto-β-boswellic acid (AKBA), the most bioactive components of boswellic acids, were used as indicators to evaluate the efficiency of self-emulsifying system. In the study of lipolysis, the aqueous solubility and bioaccessibility of KBA and AKBA were increased by 2.7 and 2.3 folds, respectively. From the in vivo pharmacokinetic study, SNES triggered a significant increase in the oral bioavailability of KBA and AKBA by 2.2 and 2.0 times higher than the bulk oil suspension, respectively. Therefore, SNES with superior storage stability is an effective oral formulation to enhance bioavailability of boswellic acids.

Design, Optimization and Evaluation of Repaglinide Self-Nanoemulsifying Drug Delivery for Enhanced Solubility

The aim of study was to develop self-nanoemulsifying systems of poorly water-soluble drug repaglinide, which is an antidiabetic drug in the class of medications known as meglitinides. Solubility of repaglinide in oily phases and surfactants was determined to identify components of self-nanoemulsifying drug delivery system (SNEDDS). Surfactants and oil was selected based on solubility studies were further screened for their efficiency in formulation. Acrysol K 150, Kolliphor EL and Capmul MCM were selected as oil, surfactant and co-surfactant respectively. Formulation F8 was found to be optimized formulation on the basis of in vitro dissolution studies, particle size and zeta potential. The optimized formulation was then subjected to stability studies and was found to be stable after 6 months. Thus, SNEDDS were found to be influential in improving the release performance of repaglinide, indicating their potential to improve the solubility and oral bioavailability of repaglinide.&#x0D;

Self-Nanoemulsifying System in the Accumulation of Resveratrol and N- Acetylcysteine in the Epidermis and Dermis

Trans-resveratrol (RES) and N-acetylcysteine (NAC) have protective effects on biological processes; therefore, they are frequently included in food supplements. Their possible applications for the prevention of free radical-induced damage to the skin are of particular physiological relevance; however, their usefulness is limited by their metabolic fate and the unpredictability of their delivery to the skin following oral administration. In this work, we evaluated the concomitant and direct application of RES and NAC on the skin using a self-nanoemulsifying system we previously developed for the oral delivery of poorly absorbed food supplements. We evaluated the capability of this system to increase RES and NAC accumulation in porcine skin using permeation studies in Franz diffusion cells. The ascorbyl palmitate (ASP) self-nanoemulsifying system considerably increased RES and NAC accumulation in the epidermis and dermis, which peaked 6 h after application. This study reveals a new formulation strategy to improve the bioavailability of ingredients, which was previously used in the health supplements field, but has rarely been employed in dermatology because of its poor distribution in the skin.

Formulation by design approach for development of ultrafine self-nanoemulsifying systems of rosuvastatin calcium containing long-chain lipophiles for hyperlipidemia management

The present work entails systematic development of liquid self-nanoemulsifying drug delivery systems (L-SNEDDS) of rosuvastatin calcium containing long-chain lipophiles using QbD-driven Formulation by Design (FbD) approach. Elements of quality target product profile (QTPP) were defined and critical material attributes (CQAs) earmarked. Excipient screening was performed for selecting a suitable long-chain lipophile along with a surfactant and a cosolvent. Maximal drug solubility was observed in Peceol (i.e., lipid), Tween 80 (i.e., surfactant) and Transcutol HP (i.e., cosolvent), which during pseudoternary phase titration study indicated maximal nanoemulsion region at 1:1 ratio of surfactant: cosolvent mixture. Risk analysis and factor screening study indicated selection of excipient levels as the critical material attributes (CMAs). D-optimal mixture design was used for systematic optimization of L-SNEDDS, which exhibited emulsification time of 131s, globule size <100nm and faster drug release rate >80% in 15min. Ex vivo permeability showed >70% permeation of drug across the rat intestine, while in situ perfusion study indicated up to 1.8 and 2.1-folds improvement in permeability and absorptivity parameters of the drug from optimized L-SNEDDS over the plain drug suspension. In vivo pharmacokinetic studies revealed 1.8- and 5.7-folds enhancement in AUC0-t and Cmax, and 0.33-folds reduction in Tmax of drug from the optimized L-SNEDDS vis-à-vis the pure plain drug suspension. In vivo pharmacodynamic studies also indicated superior antihyperlipidemic activity of optimized L-SNEDDS in normalizing serum lipid levels. Overall, the research work construed significant role of long-chain lipophiles in enhancing biopharmaceutical attributes of the L-SNEDDS of rosuvastatin.

Preparation and In-Vitro characterization of Self-Nano emulsifying system of C- Phenylcalix-[4]-Resorcinaryl Octacinnamate and C-Methylcalix-[4]-Resorcinaryl Octabenzoate as ultraviolet absorbers

Background: Sunscreens are cosmetic products which are used to protect the skin from ultraviolet (UV) rays exposure. Ultraviolet rays, especially ultraviolet B (UVB) rays can cause skin cancer. C-phenylcalix-[4]-resorcinaryl octacinnamate (compound 1) and C-methylcalix-[4]-resorcinaryl octabenzoate (compound 2) are newly synthesized compounds which have high absorbance of UVB rays. Despite their potential activity, these compounds have low solubility in water. Therefore, in order to increase the solubility, they were formulated into  a nanoemulsion.Objective: The aim of the present study was to prepare and characterize a self-nano emulsifying system of two compounds as UV absorber.Methods: Optimum formula of nanoemulsion was analyzed using D-optimal mixture design with Design Expert® ver. 7.1.5 by varying concentrations of candlenut oil, tween 80, and polyethylen glycol 400 (v/v). Sun Protection Factor (SPF), transmittance and time of emulsification were evaluated as optimization parameters. The optimal formula was further evaluated for its distribution, droplet size, and zeta potential.Results: A combination of two compounds was used in formulations and has SPF value of 52.189. The composition of optimal formula was obtained at 2.5 mL of candlenut oil, 5.066 mL of tween 80, and 2.434 mL of polyethylene glycol 400. The results showed that the optimal formula has SPF value of 81.577, % of transmittance 90.84, emulsification time of 17.42 seconds, desirability of 0.726, average droplet size of 129.9 nm with polydispersity index 0.393 and zeta potential of -15.2 mV.Conclusion: Nanoemulsion formulation using candlenut oil could increase SPF value of sunscreen compounds and potentially be used as alternative UV absorbers dosage forms in the future

A food-grade self-nanoemulsifying delivery system for enhancing oral bioavailability of ellagic acid

Ellagic acid is known of a predominant bioactive component in pomegranate that possesses broad health benefits, but it has low bioavailability. In this work, we developed a food-grade self-nanoemulsifying system to improve the dissolution and absorption of ellagic acid. Solubility assay and pseudo-ternary phase diagrams revealed suitable components for the formulation. The optimal formulation was composed of polyethylene glycol, polysorbate, caprylic/capric triacylglycerol at the ratio of 45/45/10wt.%. With this optimal formulation and gentle stirring, a fine nanoemulsion was achieved and had mean droplet size of around 120nm. The dissolution of ellagic acid was significantly elevated with the formulation. Rat pharmacokinetics studies showed that ellagic acid was 6.6- and 3.2-fold more bioavailable with the formulation than with aqueous suspensions and pomegranate extract, respectively. The proposed self-nanoemulsifying system to deliver ellagic acid can be a novel strategy for developing products for dietary supplements and functional foods of ellagic acid.

Self-Nanoemulsifying Drug Delivery System of Coenzyme (Q10) with Improved Dissolution, Bioavailability, and Protective Efficiency on Liver Fibrosis.

The aim of our investigation is to develop and characterize self-nanoemulsifying drug delivery systems (SNEDDS) of CoQ10 to improve its water solubility, dissolution rate, and bioavailability, and then evaluate its biochemical and physiological effect on liver cirrhosis in rats compared with CoQ10 powder. SNEDDS are isotropic and thermodynamically stable mixture of oil, surfactant, co-surfactant, and drug that form an oil/water nanoemulsion when added to aqueous phases with soft agitation. Upon administration, self-nanoemulsifying system becomes in contact with gastrointestinal fluid and forms o/w nanoemulsion by the aid of gastrointestinal motility. When the nanoemulsion is formed in the gastrointestinal tract, it presents the drug in a solubilized form inside small nano-sized droplets that provide a large surface area for enhancing the drug release and absorption. Solubility of CoQ10 in various oils, surfactants, and co-surfactants were studied to identify the components of SNEDDS; pseudo-ternary phase diagrams were plotted to identify the efficient self-emulsifying regions. CoQ10-loaded SNEDDS were prepared using isopropyl myristate as oil; Cremophor El, Labrasol, or Tween80 as surfactant; and Transcutol as co-surfactant. The amount of CoQ10 in each vehicle was 3%. The formulations that passed thermostability evaluation test were assessed for particle size analysis, morphological characterization, refractive index, zeta potential, viscosity, electroconductivity, drug release profile, as well as ex vivo permeability. Pharmacokinetics and hepatoprotective efficiency of the optimized SNEDDS of CoQ10 compared with CoQ10 suspension were performed. Results showed that all optimized formulae have the ability to form a good and stable nanoemulsion when diluted with water; the mean droplet size of all formulae was in the nanometric range (11.7-13.5nm) with optimum polydispersity index values (0.2-0.21). All formulae showed negative zeta potential (-11.3 to -17.2), and maximum drug loading efficiency. One hundred percent of CoQ10 was released from most formulae within 30min. One hundred percent of CoQ10 was permeated from all formulae through 10h. The pharmacokinetic study in rabbits revealed a significant increase in bioavailability of CoQ10 SNEDDS to 2.1-fold compared with CoQ10 suspension after oral administration. Comparative effect of the optimized formulae on acute liver injury compared with CoQ10 powder was also studied; it was found that all the liver biochemical markers as alanine transferase (ALT), aspartate amino transferase (AST), alkaline phosphatase (ALP), total protein (TP), and albumin were significantly improved at p < 0.05. Also, histochemical and histopthological studies confirm the biochemical results. Our results suggest the potential use of SNEDDS to increase the solubility of liphophilic drug as poorly water-soluble CoQ10 and improve its oral absorption, so it can be more efficient to improve liver damage compared to CoQ10 powder. These results demonstrated that CoQ10 SNEDDS inhibited thioacetamide (TAA)-induced liver fibrosis mainly through suppression of collagen production.

Formulation of avanafil in a solid self-nanoemulsifying drug delivery system for enhanced oral delivery

Avanafil was incorporated into solid self-nanoemulsifying systems with the aim of improving its oral bioavailability. Labrafil, Labrafac, and Miglyol 812 N were investigated as oils, Tween 80 and Cremophor EL as surfactants, and Transcutol HP as a co-surfactant. Nine formulations produced clear solutions of 13.89–38.09nm globules after aqueous dilution. Adsorption of preconcentrate onto Aeroperl 300 Pharma at a 2:1 ratio had no effect on nanoemulsion particle size. Differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy indicated that avanafil was molecularly dispersed within the solid nanosystems. A formulation containing 10% Labrafil, 60% Tween 80, and 30% Transcutol HP had the highest drug loading (44.48mg/g) and an acceptable in vitro dissolution profile (96.42% within 30min). This formulation was chemically and physically stable for 6months under accelerated storage conditions and it produced a 3.2-fold increase in bioavailability in rabbits, as compared to conventional commercially available avanafil tablets (Spedra®).

A solid self-nanoemulsifying system of the BCS class IIb drug dabigatran etexilate to improve oral bioavailability.

To develop dabigatran etexilate (DE)-loaded self-nanoemulsifying drug delivery systems (SNEDDS) for the prevention of stroke and thromboembolism. SNEDDS were optimized by ternary phase diagrams and then further solidified into dispersible tablets. In vitro dissolution was analyzed by a phase distribution study. In situ absorption and in vivo pharmacokinetic studies were tested in male Sprague-Dawley rats. The phase distribution study showed that more than 60% of DE was retained in the oil phase. Dissolution rate was dramatically enhanced without significant precipitation (<30%) in simulated intestinal fluid. Optimized SNEDDS had 531.80% relative bioavailability compared with Pradaxa(®) capsules (a commercial DE product). The developed SNEDDS are promising materials for improving the dissolution and oral bioavailability of BCS class IIb drugs.

Solid self-nanoemulsifying systems of olmesartan medoxomil: Formulation development, micromeritic characterization, in vitro and in vivo evaluation

The current studies entail development and evaluation of solid self-nanoemulsifying drug delivery systems (S-SNEDDS) employing porous carriers for enhancing the oral bioavailability of olmesartan medoxomil. Equilibrium solubility studies and pseudoternary phase diagrams revealed suitability of oleic acid, Tween 40 and Transcutol HP as the lipid, surfactant and cosolvent for formulation of the liquid SNEDDS (L-SNEDDS). The L-SNEDDS were systematically optimized using optimal mixture design, evaluated for emulsification time, globule size andin vitrodrug release. S-SNEDDS formulations were prepared by adsorbing L-SNEDDS onto the porous carriers,viz.Aerosil 200, Aeroperl 300, Sylysia 550, Neusilin US2 and Fujicalin SG, and evaluated for oil adsorption tendency, micrometric behavior, flow properties and compaction characteristics using Kawakita, Heckel and Leuenberger plots for identifying the suitable solid carrier for formulation of S-SNEDDS tablet.In vitrodissolution studies were performed for comparative analysis of the drug release behavior from the S-SNEDDS formulation. Among the various solid carriers employed, Neusilin US2 exhibited superior oil adsorbing capacity, micrometric properties, excellent flowability and compactibility. Nearly 2.6-fold improvement in the drug release rate was observed from the optimized S-SNEDDS, followed by no significant difference in the drug release rate as compared to the L-SNEDDS (p>0.05).In vivopharmacokinetic studies in Wistar rats revealed 2.32 and 3.27-fold enhancement in Cmaxand AUC of the drug from the optimized S-SNEDDSvis-à-visthe pure drug solution. Also, high degree of prognostic ability ofin vitrodissolution performance within vivoperformance was revealed from level Ain vitro/in vivocorrelations (IVIVC). In a nutshell, the present studies report successful development of S-SNEDDS of olmesartan medoxomil as one of the promising formulation strategies with distinctly improved biopharmaceutical attributes.

Enhanced oral bioavailability of 6-bromo-3-n-butylphthalide by self-nanoemulsifying system

The objectives of this study were, first, to prepare 6-bromo-3-n-butylphthalide self-nanoemulsifying system (6-BBP-SNES); and second, to enhance the water solubility and oral bioavailability of 6-BBP. Pseudo-ternary phase diagram was constructed to identify an efficient self-emulsification region. Then, formulations were optimized by assessing the globule size and polydispersity. The composition of optimized 6-BBP-SNES was 6-BBP (10% w/w), Isopropyl myristate (40.5% w/w), Polyoxyethylene hydrogenated castor oil (36% w/w) and Absolute ethanol (13.5% w/w), with the globule size (80.50 ± 0.47 nm), polydispersity (0.150 ± 0.027) and an infinite dilution capability. In vitro drug release of SNES was above 80% within 5 min, whereas that of the suspension was less than 20%. Furthermore, the Cmax of 30 mg/kg of SNES after oral administration was 1.57-fold higher than that of 100 mg/kg of 6-BBP suspension. Besides, the absolute bioavailability of SNES was found to be 47.55%, whereas that of the suspension was only 8.73%, which increased by approximately 5.45-fold. These results demonstrated SNES could be promising to improve the oral efficacy of 6-BBP, and had potential clinical application value.

Controlled release of glaucocalyxin – a self-nanoemulsifying system from osmotic pump tablets with enhanced bioavailability

Objective: The purpose of this study was to develop a new formulation to enhance the bioavailability simultaneously with controlled release of glaucocalyxin A (GLA).Material and methods: In this study, controlled release of GLA was achieved by the osmotic release strategy taking advantage of the bioavailability enhancing capacity of self-nanoemulsifying drug delivery systems (SNEDDS). The formulation of GLA-SNEDDS was selected by the solubility and pseudoternary-phase diagrams studies. The prepared GLA-SNEDDS formulations were characterized for self-emulsification time, effect of pH and robustness to dilution, droplet size analysis and zeta potential. The optimized GLA-SNEDDS were used to prepare GLA-SNEDDS osmotic pump tablet via direct powder compression method. The effect of formulation variables on the release characteristic was investigated. GLA-SNEDDS osmotic pump tablets were administered to beagle dogs and their pharmacokinetics were compared to GLA and GLA-SNEDDS as a control.Results: In vitro drug release studies indicated that the GLA-SNEDDS osmotic pump tablet showed sustained release profiles with 90% released within 12 h. Pharmacokinetic study showed steady blood GLA with prolonged Tmax and mean residence time (MRT), and enhanced bioavailability for GLA-SNEDDS osmotic pump tablet.Conclusion: It was concluded that simultaneous controlling on GLA release and enhanced bioavailability had been achieved by a combination of osmotic pump tablet and SNEDDS.

Nanostructured Delivery Systems: Augmenting the Delivery of Antiretroviral Drugs for Better Management of HIV/AIDS

In the last two decades, HIV-1, the retrovirus associated with acquired immunodeficiency syndrome (AIDS), is globally one of the primary causes of morbidity and mortality. Unfortunately, existing approaches for interventions are not able to suppress the progression of infection due to this virus. Of the many obstacles, viral entry into the mono-nuclear phagocyte system encompassing monocytes/macrophages and dendritic cells is a major concern. Viral infection is also responsible for the subsequent distribution of the virus into various tissues throughout the organism. Tremendous progress has been made during the past few years to diagnose and treat patients with HIV/AIDS infection, yet much remains to be done. Recommended treatment involves long-term and multiple drug therapy that causes severe side effects. With almost 12% of the world population suffering from HIV/AIDS, better management of this global threat is highly desired. Nanostructured delivery systems hold promise for improving the situation. Such systems can facilitate the uptake of antiretroviral drugs, causing a considerable improvement in HIV/AIDS therapy. Nanoscale systems have intriguing potential to drastically improve existing HIV/AIDS diagnosis and treatment platforms. Nanosystems constitute a wide range of systems varying from polymeric nanoparticles, to solid-lipid nanoparticles, liposomes, micro- and nanoemulsions, dendrimers, and self-nanoemulsifying systems. Improved bioavailability, solubility, stability, and biocompatibility make them an ideal choice for delivery of antiretroviral drugs. The present review initially describes an updated bird's-eye view account of the literature. Then, we provide a relatively sententious overview on updated patents of recent nanostructured delivery systems for antiretroviral drugs. Finally, we discuss low-cost therapy (such as antioxidants and immune modulators) for the treatment and prevention of HIV/AIDS.