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Empagliflozin (EFZ), a sodium-glucose co-transporter 2 (SGLT2) inhibitor used to treat type 2 diabetes, faces challenges with poor solubility and bioavailability. This study aimed to evaluate a Self-Nanoemulsifying Drug Delivery System (SNEDDS), specifically SN1C, for enhancing EFZ's dissolution rate and pharmacokinetics compared to pure EFZ powder and a marketed tablet (MKT). We assessed dissolution profiles in vitro and conducted pharmacokinetic studies in rats following oral administration of the three formulations. Plasma samples were analyzed using LC-MS/MS, and pharmacokinetic parameters were determined via non-compartmental analysis. SN1C demonstrated the highest dissolution rate in vitro. In vivo, SN1C achieved a significantly higher maximum plasma concentration (Cmax) and area under the curve (AUC(inf)) than EFZ and MKT, with approximately 1.5-fold higher Cmax and a significantly greater AUC(inf) (p < 0.05). Tmax and half-life (t1/2) were similar across all formulations, indicating that SNEDDS did not negatively impact these parameters. The results suggest that SN1C substantially improves the bioavailability of EFZ, highlighting the efficacy of SNEDDS technology in enhancing the oral delivery and therapeutic effectiveness of poorly soluble drugs like EFZ. [ABSTRACT FROM AUTHOR]

The present study aimed to develop and optimize solidified supersaturated self-nanoemulsifying drug delivery systems (SNEDDS) for the combined administration of antihypertensive, antihyperglycemic, and antihyperlipidemic drugs to enhance their solubility and dissolution during the treatment of metabolic syndrome. Various SNEDDS formulations were prepared and subjected to pharmaceutical assessment. The solubility of candesartan (CC), glibenclamide (GB), and rosuvastatin (RC) in SNEDDS and supersaturated SNEDDS formulations was evaluated. The optimized formulation was solidified using Syloid adsorbent at different ratios. Pharmaceutical characterization of the formulations included particle size, zeta potential, in-vitro dissolution, PXRD, FTIR, and SEM analysis. The prepared optimized formulation (F6) was able to form homogeneous nanoemulsion droplets without phase separation, which is composed of Tween 20: PEG-400: Capmul MCM (4: 3: 3). It was mixed with 5% PVP-K30 to prepare a supersaturated liquid SNEDDS formulation (F9). In addition, it was found that the addition of PVP-K30 significantly increased solubility CC and GB from 20.46 ± 0.48 and 6.73 ± 0.05 to 27.67 ± 1.72 and 9.45 ± 0.32 mg/g, respectively. In-vitro dissolution study revealed that liquid and solid SNEDD formulations remarkably improved the dissolution rates of CC, GB, and RC compared to pure drugs. XRPD and FTIR analysis revealed that all drugs present in an amorphous state within prepared solidified supersaturated SNEDDS formulation. SEM images showed that liquid SNEDDS formulation was successfully adsorbed on the surface of Syloid. Overall, optimized F9 and solidified supersaturated SNEDDS formulations showed superior performance in enhancing drug solubility and dissolution rate. The present study revealed that the proposed triple combination therapy of metabolic syndrome holds a promising strategy during the treatment of metabolic syndrome. Further in-vivo studies are required to evaluate the therapeutic efficacy of prepared solidified supersaturated SNEDDS formulation. [ABSTRACT FROM AUTHOR]

The aim of this work is to develop and evaluate self-nanoemulsifying drug delivery systems (SNEDDS) containing simvastatin to increase its oral bioavailability. Formulation EO 5 (Ethyl oleate 9.3% w/w: Tween 80 49.4% w/w: Propylene glycol 39.3% w/w) and Formulation CL 14 (Clove oil 54.3% w/w: Tween 80 34.4% w/w: Transcutol-P 9.3% w/w) were thoroughly studied. They showed emulsification time less than 1 min, droplet size in the nanometric range, and almost a complete drug release after 2 h. The in-vitro dissolution profile of both formulations was found to be significant in comparison to the pure drug in pH 1.2 and 7.4 buffers (P < 0.0001). Furthermore, they demonstrated superior anti-hyperlipidemic activity in comparison to simvastatin suspension (10 mg/kg/day). In order to investigate the impact of oil type on oral bioavailability, the selected formulations have been examined in terms of the in-vivo pharmacokinetic study, and formulation EO 5 was found to have higher bioavailability. After oral administration of a single dose (40 mg/kg) of simvastatin-loaded SNEDDS (CL14 and EO 5), a 1.5-fold and 1.95-fold increase in bioavailability were observed, respectively, as compared to simvastatin suspension. Hence, the results indicated that the developed SNEDDS could enhance the therapeutic efficacy and oral bioavailability of simvastatin. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of SNEDDS containing Curcuma longa extract on hormonal and histological improvement of polycystic ovary syndrome (PCOS) rat model. Method: A total of 36 female Wistar rats, aged between 8 and 10 weeks, were randomly divided into 6 groups, including control (normal rats), PCOS (untreated PCOS rats), PCOS + M (treated with 20 mg/kg bw/day metformin), PCOS + SC25, PCOS + SC50, and PCOS + SC100 (treated with Curcuma longa extract at 25, 50, and 100 mg/kg/day with SNEDDS, respectively). This study used a posttest-only control group design. The rats were euthanized on day 15, and blood samples were taken to examine malondialdehyde (MDA) and anti-mullerian hormone (AMH) levels. Ovarian tissue was prepared on a histological slide, and various follicles were observed. Data was analyzed using analysis of variance (ANOVA) and Kruskal-Wallis tests. Results: Curcuma longa extract, at 50 and 100 mg/kg, incorporated in SNEDDS resulted in a significant reduction in the corpus luteum number and width of the granulosa layer (p < 0.05). Also, Curcuma longa significantly reduced malondialdehyde (MDA), anti-mullerian hormone (AMH), preantral follicles, and follicular cysts (p < 0.05). Conclusion: Curcuma longa extract in SNEDDS reduces MDA and AMH levels and improves the histology of the ovaries in PCOS model rats. There is a need to conduct further studies of C. longa extract or isolates in SNEDDS using human cell lines of PCOS model. [ABSTRACT FROM AUTHOR]

The gut microbiome is involved in the pathogenesis of many diseases including polycystic ovarian syndrome (PCOS). Modulating the gut microbiome can lead to eubiosis and treatment of various metabolic conditions. However, there is no proper study assessing the delivery of microbial technology for the treatment of such conditions. The present study involves the development of guar gum-pectin-based solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing curcumin (CCM) and fecal microbiota extract (FME) for the treatment of PCOS. The optimized S-SNEDDS containing FME and CCM was prepared by dissolving CCM (25 mg) in an isotropic mixture consisting of Labrafil M 1944 CS, Transcutol P, and Tween-80 and solidified using lactose monohydrate, aerosil-200, guar gum, and pectin (colon-targeted CCM solid self-nanoemulsifying drug delivery system [CCM-CT-S-SNEDDS]). Pharmacokinetic and pharmacodynamic evaluation was carried out on letrozole-induced female Wistar rats. The results of pharmacokinetic studies indicated about 13.11 and 23.48-fold increase in AUC of CCM-loaded colon-targeted S-SNEDDS without FME (CCM-CT-S-SNEDDS (WFME)) and CCM-loaded colon-targeted S-SNEDDS with FME [(CCM-CT-S-SNEDDS (FME)) as compared to unprocessed CCM. The pharmacodynamic study indicated excellent recovery/reversal in the rats treated with CCM-CT-S-SNEDDS low and high dose containing FME (group 13 and group 14) in a dose-dependent manner. The developed formulation showcasing its improved bioavailability, targeted action, and therapeutic activity in ameliorating PCOS can be utilized as an adjuvant therapy for developing a dosage form, scale-up, and technology transfer. [ABSTRACT FROM AUTHOR]

Abstract The aim of this work is to develop and evaluate self-nanoemulsifying drug delivery systems (SNEDDS) containing simvastatin to increase its oral bioavailability. Formulation EO 5 (Ethyl oleate 9.3% w/w: Tween 80 49.4% w/w: Propylene glycol 39.3% w/w) and Formulation CL 14 (Clove oil 54.3% w/w: Tween 80 34.4% w/w: Transcutol-P 9.3% w/w) were thoroughly studied. They showed emulsification time less than 1 min, droplet size in the nanometric range, and almost a complete drug release after 2 h. The in-vitro dissolution profile of both formulations was found to be significant in comparison to the pure drug in pH 1.2 and 7.4 buffers (P

Camila Faria de Amorim Pereira,1,&ast; Michelle Nonato de Oliveira Melo,1,&ast; Vania Emerich Bucco de Campos,2 Ivania Paiva Pereira,1 Adriana Passos Oliveira,1 Mariana Souza Rocha,1 João Vitor da Costa Batista,3,4 Valter Paes de Almeida,5 Irailson Thierry Monchak,5 Eduardo Ricci-Júnior,6 Rafael Garrett,7 Aline Gabrielle Alves Carvalho,7 Jane Manfron,5 Stephan Baumgartner,3,8,9 Carla Holandino1,3 1Multidisciplinary Laboratory of Pharmaceutical Sciences, Faculty of Pharmacy, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 2Department of Pharmacy, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil; 3Society for Cancer Research, Hiscia Institute, Arlesheim, Switzerland; 4Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Basel, Switzerland; 5Postgraduate Program in Pharmaceutical Sciences, Universidade Estadual de Ponta Grossa, Ponta Grossa, Paraná, Brazil; 6Galenic Development Laboratory (LADEG), Department of Drugs and Medicines, Faculty of Pharmacy, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 7Metabolomics Laboratory, Chemistry Institute, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 8Institute of Integrative Medicine, University of Witten/Herdecke, Herdecke, Germany; 9Institute of Complementary and Integrative Medicine, University of Bern, Bern, Switzerland&ast;These authors contributed equally to this workCorrespondence: Carla Holandino, Multidisciplinary Laboratory of Pharmaceutical Sciences, Universidade Federal do Rio de Janeiro, Faculty of Pharmacy, Block B basement, Room 34, 373, Carlos Chagas Filho Avenue, Cidade Universitária, Rio de Janeiro, RJ, 21941-902, Brazil, Email cholandino@gmail.com Stephan Baumgartner, Institute of Complementary and Integrative Medicine, University of Bern, Bern, Switzerland, Email St.Baumgartner@vfk.chBackground and Purpose: Natural products are potential sources of anticancer components. Among various species, the lipophilic extract of the Viscum album subsp. austriacum (Wiesb.) Vollm. (VALE) has shown promising therapeutic potential. The present work aimed to qualify the plant source and characterize the extract’s chemical profile. In addition, a self-nanoemulsifying drug delivery system (SNEDDS) containing VALE (SNEDDS-VALE) was developed.Methods: V. album subsp. austriacum histochemistry was performed, and the chemical profile of VALE was analyzed by GC-MS. After the SNEEDS-VALE development, its morphology was visualized by transmission electron microscopy (TEM), while its stability was evaluated by the average droplet size, polydispersity index (PdI) and pH. Lastly, SNEDDS-VALE chemical stability was evaluated by LC-DAD-MS.Results: The histochemical analysis showed the presence of lipophilic compounds in the leaves and stems. The major compound in the VALE was oleanolic acid, followed by lupeol acetate and ursolic acid. SNEDDS was composed of medium chain triglyceride and Kolliphor® RH 40 (PEG-40 hydrogenated castor oil). A homogeneous, isotropic and stable nanoemulsion was obtained, with an average size of 36.87 ± 1.04 nm and PdI of 0.14 ± 0.02, for 14 weeks.Conclusion: This is the first histochemistry analysis of V. album subsp. austriacum growing on Pinus sylvestris L. which provided detailed information regarding its lipophilic compounds. A homogeneous, isotropic and stable SNEDDS-VALE was obtained to improve the low water solubility of VALE. Further, in vitro and in vivo experiments should be performed, in order to evaluate the antitumoral potential of SNEDDS-VALE. Keywords: Viscum album subsp. austriacum, mistletoe, lipophilic extract, oleanolic acid, SNEDDS

Peptic ulcer disease (PUD) adversely affects ≈4 million individuals globally and remains pervasive among 5–10% of the general population. Mucosal lesions prompted by the ulceration lead to the penetration through mucosal layers, ultimately resulting in cavity formation and inflammation. Conventional therapeutic modalities for peptic ulcers have shown unfavorable effects, relapses, and numerous drug interactions. The genesis of gastric ulcers is catalyzed via an imbalanced interplay between environmental lesions, defensive mechanisms, and the restoration of gastric mucosa. Lipid based nanotechnology involved in self‐nanoemulsifying drug delivery system (SNEDDS) is being tremendously involved in opening avenues in innovative pharmaceutical delivery systems in terms of improving solubility and regenerative healing against peptic ulcers. Biological macromolecules can be incorporated into SNEDDS to embellish the drug delivery system on an advanced level. Herein, in this review, the potential of SNEDDS as a viable carrier for administering biomacromolecules for regenerative healing in ulcers is discussed in detail. [ABSTRACT FROM AUTHOR]

Beta-carotene is an antioxidant compound that benefits health by boosting immunity and preventing chronic diseases. However, beta-carotene has low solubility (practically insoluble in water) and bioavailability, so it will produce a poor beneficial effect. An alternative candidate that may overcome this problem is a self-nanoemulsifying drug delivery system (SNEDDS). SNEDDS can enhance the oral bioavailability of poorly soluble active compounds by increasing the solubility and stability of active compounds in oil droplets. This study aims to develop beta-carotene SNEDDS by determining the optimum composition of SNEDDS. The low-energy method and simplex lattice design (SLD) were combined to determine the optimum formula. Based on the results, the solubility of beta-carotene in sesame oil, polysorbate 80, and PEG 400 as components of SNEEDS were 0.455 mg/mL, 1.538 mg/mL, and 0.667 mg/mL, respectively. The optimum formula of beta-carotene SNEDDS had a mixing ratio of sesame oil and surfactant mixture in 1:15.2 (v/v), emulsification time of 38.48 ± 0.70 seconds, the droplet size of 13.13 ± 0.50 nm, and size distribution (PdI) of 0.133 ± 0.06. The optimum formula of beta-carotene SNEDDS had good stability in the artificial gastric fluid after 4 hours of incubation. Moreover, the optimum beta-carotene SNEDDS formula had high stability during storage at room temperature and 40oC ± 2oC/75%RH±5%RH. [ABSTRACT FROM AUTHOR]

Atazanavir or ATV is an FDA-approved, HIV-1 protease inhibitor that belongs to the azapeptide group. Over time, it has been observed that ATV can cause multiple adverse side effects in the form of liver diseases including elevations in serum aminotransferase, indirect hyper-bilirubinemia, and idiosyncratic acute liver injury aggravating the underlying chronic viral hepatitis. Hence, there is an incessant need to explore the safe and efficacious method of delivering ATV in a controlled manner that may reduce the proportion of its idiosyncratic reactions in patients who are on antiretroviral therapy for years. In this study, we assessed ATV formulation along with Rosemary oil to enhance the anti-HIV-1 activity and its controlled delivery through self-nanoemulsifying drug delivery system or SNEDDS to enhance its oral bioavailability. While the designing, development, and characterization of ATV-SNEDDS were addressed through various evaluation parameters and pharmacokinetic-based studies, in vitro cell-based experiments assured the safety and efficacy of the designed ATV formulation. The study discovered the potential of ATV-SNEDDS to inhibit HIV-1 infection at a lower concentration as compared to its pure counterpart. Simultaneously, we could also demonstrate the ATV and Rosemary oil providing leads for designing and developing such formulations for the management of HIV-1 infections with the alleviation in the risk of adverse reactions. [ABSTRACT FROM AUTHOR]

Breast cancer is reported as one of the most prevalent non-cutaneous malignancies in women. Venetoclax (VEN) is an approved BCl-2 inhibitor for the treatment of chronic myeloid leukemia with very limited oral bioavailability and exhibits an enormous impact on breast cancer. In the current investigation, venetoclax-loaded self-nanoemulsifying drug delivery systems (VEN-SNEDDS) were designed and fabricated to improve the aqueous solubility, permeability, and anticancer efficacy of VEN. Various surface-active parameters of the reconstituted SNEDDS were determined to scrutinize the performance of the selected surfactant mixture. Central composite design (CCD) was used to optimize the VEN-SNEDDS. The globule size of reconstituted VEN-SNEDDS was 71.3 ± 2.8 nm with a polydispersity index of 0.113 ± 0.01. VEN-SNEDDS displayed approximately 3–4 fold, 6–7 fold, and 5–6 fold reduced IC50 as compared to free VEN in MDA-MB-231, MCF-7, and T47 D cells, respectively. VEN-SNEDDS showed greater cellular uptake, apoptosis, reactive oxygen species generation, and higher BAX/BCL2 ratio with decreased caspase 3 and 8 and BCL-2 levels in the MDA-MB-231 cells compared to pure VEN. VEN-SNEDDS exhibited approximately fivefold enhancement in Cmax and an improved oral bioavailability compared to VEN suspension in in vivo pharmacokinetic studies. [ABSTRACT FROM AUTHOR]

ABSTRACT: In the antibiotic-free era, traditional antibiotics have been suggested as alternatives to antibiotic-based growth promoters. Among the various methods, self-nano-emulsifying drug delivery systems (SNEDDS) are increasingly utilized to improve the bioavailability of oils containing essential substances. In this study, we evaluated the effects of black soldier fly oil (BSFO) SNEDDS in chicken drinking water on growth performance, small intestine histomorphology, and poultry health status. We divided 225 male Indian River strain broiler chickens into five treatment groups, each consisting of 5 replicates. The chickens were reared from to 0 to 35 d of age in a controlled environmental housing system. The BSFO SNEDDS was administered via drinking water. Treatments included ordinary drinking water (P1), bacitracin (P2), and 10 mL/L (P3), 20 mL/L (P4), and 30 mL/L (P5) BSFO SNEDDS. The observed parameters included growth performance, carcass yield, blood hematology, intestinal histomorphology, digestive microflora, and immunoglobulin (Ig) levels. Data were analyzed using analysis of variance (ANOVA) and Duncan's test. The results indicated that administering BSFO SNEDDS via drinking water improved feed conversion (P < 0.05), enhanced the performance index (P < 0.05), increased carcass percentage (P < 0.001), and increased the weight of the carcass parts. Additionally, it increased villus height (P < 0.01), lowered jejunal pH (P < 0.001), reduced pathogenic bacteria in the jejunum, and decreased the leukocyte count. BSFO SNEDDS in drinking water is expected to be used as a traditional antibiotic with the potential to replace synthetic antibiotic growth promoters in broiler chickens.

Owing to deprived hydrophilicity, Artemisinin (ART) is known as Class II biopharmaceutical (BCS). The goal of the existing endeavor is to formulate ART self-nanoemulsifying drug delivery systems (ART-SNEDDS) that will increase its solubility in water. Thus, excipients were screened in pre-formulation experiments for solubility and emulsification effectiveness. Moreover, blends of the oil soy bean, surfactant tween 80 and co-surfactant soy lecithin were used to create pseudo ternary phase diagrams at different ratios. Further, the prepared ART-SNEDDS were evaluated visually, for thermodynamic stability, time to self nano-emulsify, the impact of dilution and pH, % transmittance, droplet size, poly dispersity index (PDI), surface morphology studies, zeta potential, in-vitro release rate, and for oral pharmacokinetic studies. The ART-SNEDDS were prepared to increase the quantity of loaded ART into the formulation. Nevertheless, in-vitro dissolution studies of the ART-SNEDDS formulation demonstrated an increased dissolution with improved solubility. It was found through oral bio-availability experiments in rats that there was an improvement in rate of absorption as well. As a result, a formulation to increase the drug's solubility and perhaps bioavailability was developed. [ABSTRACT FROM AUTHOR]

Metabolic syndrome is an associated condition that occurs together and increases the risk of heart disease and diabetes. These conditions include high blood pressure, high blood sugar, and high body mass index (BMI) in terms of cholesterol and triglyceride levels. Most of the elderly population may administer three drugs to control the above conditions. Therefore, this study aims to develop an analytical assay for the precise analysis of three components and to formulate a Self-Nanoemulsifying Drug-Delivery System (SNEDDS) loaded with three drugs: Rosuvastatin Calcium (RC; antilipidemic), Glibenclamide (GB; antidiabetic), and Candesartan Cilexetil (CC; antihypertensive). A design of the experiment was developed at a level of 32, and the influence of column temperature and flow rate was studied in terms of retention time, peak area, peak asymmetry, and resolution. The assay was subjected to several studies to ensure its validation. Under the optimized conditions—column temperature at 50 °C and flow rate at 0.25 mL/min—the three drugs, RC, GB, and CC, are separated. Their retention times are 0.840, 1.800, and 5.803 min, respectively. The assay was valid in terms of linearity, accuracy, and precision. Moreover, the developed assay shows a good tolerance against any change in the condition. The assay was tested also to separate the drugs in a pharmaceutical formulation as SNEDDs. The assay successfully separates the drug with a good resolution. [ABSTRACT FROM AUTHOR]

This research focuses on optimizing and stabilizing the essential oil of fingerroot (Boesenbergia rotunda), a plant native to Indonesia, using a selfnanoemulsifying drug delivery system (SNEDDS) technology. This essential oil possesses antimicrobial, anti-inflammatory, and antifungal properties, making it a potential alternative to synthetic antibiotics. However, its low bioavailability and volatility limit its usage. The study involved two stages: nanoemulsion creation by D-Optimal method using Design Expert software version 13 and stability analysis of bioactive compounds through gas chromatography-mass spectrometry (GC-MS). The optimized formula consisted of fingerroot essential oil, virgin coconut oil (VCO), Tween 80, and Polyethylene Glycol (PEG) 400 in percentages of 12.61%, 12.61%, 53.65%, and 21.12%, respectively. Prior to nanoemulsion, the essential oil contained 28.29% camphor and 27.13% 1,8-cineole, which are the highest bioactive compounds. After applying the SNEDDS technology, the camphor content decreased to 25.17%, while the 1,8-cineole content reduced to 13.05%. These findings indicate that while the concentration of bioactive compounds in fingerroot essential oil decreases, the oil itself facilitates its potential application in pharmaceutical and therapeutic fields as SNEDDS base, characterized by valuable particle size and polydispersity index (PDI). [ABSTRACT FROM AUTHOR]

Aims: Mycobacterium tuberculosis and Pseudomonas aeruginosa are still a problem in the world. This study was aimed to develop the self-nano emulsifying drug delivery system (SNEDDS) formulation of red betel vine leaf ethanol extract, which has the potential as an antibacterial agent against M. tuberculosis and P. aeruginosa. Methodology and results: Red betel vines were extracted using the maceration method with 70% ethanol. SNEDDS ethanol extract was prepared using high-energy and low-energy methods, while the formulation was evaluated in the form of % transmittance, particle size, polydispersion index and zeta potential to accelerated stability tests. The SNEDDS formula of the extract, passing the stability test, was further tested for accelerated antibacterial activity. The presence of M. tuberculosis was tested using the resazurin microtiter assay (REMA) method, while P. aeruginosa was tested using the dilution method by determining the minimum bactericidal concentration (MBC) value. In this study, the SNEDDS formula of the extract, which included nanoemulsion, had a particle size of 16-17 nm (<200 nm), PI 0.52-0.55 D (<0.7 D), zeta potential -18.03-24.96 mV (<30 mV) and % transmittance of 94-96% (>90%). MBC of SNEDDS formula against M. tuberculosis becomes apparent at concentrations <1%, whereas in the case of P. aeruginosa, this phenomenon is observed at a concentration as low as 0.0312%. Conclusion, significance and impact of study: Research findings suggest that the SNEDDS formula of red betel vine leaf ethanol extract was stable and has the potential as an antibacterial agent against M. tuberculosis and P. aeruginosa. [ABSTRACT FROM AUTHOR]

Introduction: Rosuvastatin is a statin drug used to lower cholesterol, but it has poor water solubility and low bioavailability, limiting how effective it can be. The objective of the present study was to formulate and evaluate a SNEDDS "self-nano emulsifying drug delivery systems" of Rosuvastatin and to optimize its formulation. Materials and Methods: The SNEDDS was produced using Egg lecithin, Capmul MCM, and Tween 20 as co-surfactant, oil, and surfactant, respectively. The formulation was optimized by Design Expert 12 and was characterized by various techniques such as globule size, zeta potential, % transmittance, refractive index, drug release studies etc. The optimized SNEDDS was loaded with different adsorbents by adsorption using technique and characterized for in vitro release studies, in vivo drug release studies and comparison studies with pure drug. Results: The SNEDDS were optimized which shows a negative zeta potential of -4.32, a globule size of 42.21 nm, and a faster release compared to other formulations. Drug release studies (in vitro) showed that the optimized SNEDDS-loaded tablet had more rapid rate of drug release (99.9% at 40 min) when compared with the pure drug (36.73% at 40 min). The in vivo study in healthy rabbits showed a highest release rate of drug from the SNEDDS loaded tablet (RRSV1) when compared with the pure drug resulting in an enhanced bioavailability of Rosuvastatin. Conclusion: The study concludes that the SNEDDS of Rosuvastatin is a promising approach for increasing solubility, rate of dissolution and bioavailability. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated that Sirtuin-1 (SIRT-1)-activating molecules exert a protective role in degenerative ocular diseases. However, these molecules hardly reach the back of the eye due to poor solubility in aqueous environments and low bioavailability after topical application on the eye's surface. Such hindrances, combined with stability issues, call for the need for innovative delivery strategies. Within this context, the development of self-nanoemulsifying drug delivery systems (SNEDDS) for SIRT-1 delivery can represent a promising approach. The aim of the work was to design and optimize SNEDDS for the ocular delivery of two natural SIRT-1 agonists, resveratrol (RSV) and melatonin (MEL), with potential implications for treating diabetic retinopathy. Pre-formulation studies were performed by a Design of Experiment (DoE) approach to construct the ternary phase diagram. The optimization phase was carried out using Response Surface Methodology (RSM). Four types of SNEDDS consisting of different surfactants (Tween® 80, Tween® 20, Solutol® HS15, and Cremophor® EL) were optimized to achieve the best physico-chemical parameters for ocular application. Stability tests indicated that SNEDDS produced with Tween® 80 was the formulation that best preserved the stability of molecules, and so it was, therefore, selected for further technological studies. The optimized formulation was prepared with Capryol® PGMC, Tween® 80, and Transcutol® P and loaded with RSV or MEL. The SNEDDS were evaluated for other parameters, such as the mean size (found to be ˂50 nm), size homogeneity (PDI < 0.2), emulsion time (around 40 s), transparency, drug content (>90%), mucoadhesion strength, in vitro drug release, pH and osmolarity, stability to dilution, and cloud point. Finally, an in vitro evaluation was performed on a rabbit corneal epithelial cell line (SIRC) to assess their cytocompatibility. The overall results suggest that SNEDDS can be used as promising nanocarriers for the ocular drug delivery of RSV and MEL. [ABSTRACT FROM AUTHOR]

The epimedium plant (Epimedium brevicornum Maxim) has activity as an aphrodisiac derived from a flavonoid compound, namely icariin. Icariin has low solubility and bioavailability. The utilization of icariin using the SNEDDS (Self Nanoemulsifying Drug Delivery System) method is expected to increase the solubility and bioavailability of icariin. This study aims to determine the optimum formula, characteristics, physical properties, and aphrodisiac activity of SNEDDS icariin. The optimum formula used is tween 80 (75%): PEG 400 (12.5%) and cucut fish oil (12.5%). The characteristics of SNEDDS icariin obtained were droplet size with an average of 15.63±0.058 nm, PI 0.144±0.062, zeta potential -22.67±2.06 mV, emulsification time 12.30 seconds, and transmittance 97.2%. The physical test of SNEDDS icariin produced in the form of a clear preparation in yellow color, pH 6.52, the viscosity of 120 cps, as well as the SNEDDS icariin dissolution in aqueous media in the 60th minute was 75.40% colluded. SNEDDS icariin dose 50 mg/KgBW has a better aphrodisiac effect than pure icariin 100 mg/kgBW. [ABSTRACT FROM AUTHOR]

Vemurafenib (VMF) is a practically insoluble (< 0.1 μg/mL) and least bioavailable (1%) drug. To enhance its oral bioavailability and solubility, we formulated a reliable self-nano emulsifying drug delivery system (SNEDDS). A Quality by Design (QbD) approach was used to optimize the ratio of Capryol 90, Tween 80, and Transcutol HP. VMF-loaded SNEDDS was characterized for its size, polydispersity index (PDI), zeta potential, drug content, and transmittance. The in vitro release profile of the drug loaded in SNEDDS was compared to the free drug in two media, pH 6.8 and 1.2, and the data obtained were analyzed with different mathematical models. A reverse-phase ultra-pressure liquid chromatography (UPLC) technique with high sensitivity and selectivity was developed and validated for the quantification of VMF in analytical and bioanalytical samples. Dissolution efficiency for SNEDDS was estimated using different models, which proved that the developed novel SNEDDS formulation had a better in vitro dissolution profile than the free drug. A 2.13-fold enhanced oral bioavailability of VMF-loaded SNEDDS compared to the free drug demonstrates the superiority of the developed formulation. This work thus presents an overview of VMF-loaded SNEDDS as a promising alternative to improve the oral bioavailability of the drug. [ABSTRACT FROM AUTHOR]

Immunity jamu consists of ginger, turmeric, Centella, and cinnamon, that act as immunostimulant agents. However, the infusion is impractical and used a limited dose of the extract, so it is necessary to develop drug delivery to resolve that problem. The SNEDDS technique is expected to increase the solubility, drug release, and absorption of active substances in the body, especially for low solubility of an active substance. SNEDDS consists of oil, surfactant, and co-surfactant. A surfactant is a substance that can reduce surface tension so that emulsion globules form in nanoparticle size. Tween 80 can produce a more transparent solution for oil-in-water emulsions than surfactants with low HLB values. This study aimed to determine the effect of surfactant concentration on the physical properties of SNEDDS to obtain the most loading dose but the smallest particle size. The formula consists of tamanu oil tween 80-propylene glycol of 1:7:1; 1:8:1; and 1:9:1 that incorporated extracts were 75, 150, and 375 mg. The physical tests included transmittance percentage, emulsification time on AGF media, phase separation, and stability test using the cycling test method. SNEDDS, then followed by the Particle Size Analyzer test. The results showed that the greater surfactant concentration produced a better transmittance value, a faster emulsification time, and stability. Formula with oil: surfactant: co-surfactant of 1:8:1 is a system that meets the requirement for immunity jamu with an optimal loading dose and small particle size compared to another formula. The extract’s loading dose of 375 mg has a particle size of 27.17 nm and a polydispersity index of 0.25.

Piroxicam belongs to BCS class II and has low solubility. Self-nanoemulsifying drug delivery systems (SNEDDS) are considered a potential approach for increasing the solubility and release of piroxicam. This study aimed to select the components and component ratios of piroxicam SNEDDS using fractional factorial design 26-2 (FFD). The variables used in the DFT development of piroxicam SNEDDS are the type and concentration of oil (triacetin and oleic acid), surfactant (kolliphor EL and Tween 60), and co-surfactants (Transcutol and PEG 400). The FFD results showed 16 runs with different proportions of the piroxicam SNEDDS components, which were then characterized by critical parameters including emulsification time, %transmittance, droplet size, and drug loading. The components and component ratios of the PKM SNEDDS were determined using single-factor plot analysis. The results showed that triacetin (oil), kolliphor EL (surfactant), Transcutol (co-surfactant) had the greatest contribution to the formation of piroxicam SNEDDS with an oil ratio range of 11.11–28.57%, surfactant 44.44–77.78%, co-surfactant 11.11–44.44 %.

The research was undertaken to design, develop and characterize the smart lipid system of an inadequate bioavailable Atovaquone (ATQ). The poor aqueous solubility and dissolution are the major constrain of inadequate bioavailability. The solubility study reveals that Labrasol-ALF (L-ALF), Tween 80, and Trancutol®P (TP) were screened as oil, surfactant, and co-surfactant, respectively. The pseudo ternary diagram was constructed to locate the appropriate amount of each ingredient, and a 1:3:1 ratio of l-ALF: Tween 80: TP was chosen. The effect of precipitation inhibitor was assessed using the parachute effect. Soluplus® (SP) was chosen as a precipitation inhibitor at 5%. Ishikawa diagram and qualitative risk assessment were performed to screen the critical material attributes (CMAs) and critical process parameters (CPPs). d-optimal mixture design was explored for the optimization of the formulation. The amount of oil, surfactant, and co-surfactant was screened as independent variables, whereas globule size, poly-dispersibility index (PDI), and solubility were designated dependent variables. The design batches were evaluated for the in-vitro dissolution rate, PDI, zeta potential, globule size, etc. The optimal region was located using an overlay plot. The optimized formulation has shown a 97.91% drug release within 1 h. The value of zeta potential (-27.43 mV) and PDI (0.468) indicates the stability of the formulation. The parachute effect had explored for the selection of precipitation inhibitors. SP was able to increase the solubility of ATQ and reduce the precipitation of the drug. The amount of l-ALF, Tween, 80and TP was significant for the formulation of SNEDDS. The formulation was novel, effective, patient-friendly, and industry oriented.

Miconazole is a synthetic derivative of imidazole, a medication with a broad-spectrum antifungal agent that is used to treat localized vaginal, skin, and nail infections. The aim of the study was to develop an innovative technique to improve the permeability and efficacy of topical miconazole nitrate. A nanoemulgel of miconazole nitrate was formulated by the incorporation of a nanoemulsion and a hydrogel. The nanoemulsion was first optimized using a self-emulsifying technique, and the drug was then loaded into the optimum formulation and evaluated prior to mixing with the hydrogel. Miconazole nitrate nanoemulgel formulations were evaluated for their physical characteristics and antifungal activity. Based on the results, the formulation with 0.4 % Carbopol showed the highest release profile (41.8 mg/ml after 2 h); thus, it was chosen as the optimum formulation. A cell diffusion test was performed to examine the ability of the Miconazole nitrate nanoemulgel to penetrate the skin and reach the bloodstream. Percentage cumulative drug releases of 29.67 % and 23.79 % after 6 h were achieved for the MNZ nanoemulgel and the commercial cream, Daktazol, respectively. The antifungal activity of the novel MNZ nanoemulgel formulation was tested against Candida albicans and compared to Daktazol cream and almond oil; the results were: 40.9 ± 2.3 mm, 25.4 ± 2.7 mm and 18 ± 1.9 mm, respectively. In conclusion, a novel MNZ nanoemulgel showing superior antifungal activity compared to that of the commercial product has been developed. This nanotechnology technique is a step toward making pharmaceutical dosage forms that has a lot of promise.

Metabolic syndrome is an associated condition that occurs together and increases the risk of heart disease and diabetes. These conditions include high blood pressure, high blood sugar, and high body mass index (BMI) in terms of cholesterol and triglyceride levels. Most of the elderly population may administer three drugs to control the above conditions. Therefore, this study aims to develop an analytical assay for the precise analysis of three components and to formulate a Self-Nanoemulsifying Drug-Delivery System (SNEDDS) loaded with three drugs: Rosuvastatin Calcium (RC; antilipidemic), Glibenclamide (GB; antidiabetic), and Candesartan Cilexetil (CC; antihypertensive). A design of the experiment was developed at a level of 32, and the influence of column temperature and flow rate was studied in terms of retention time, peak area, peak asymmetry, and resolution. The assay was subjected to several studies to ensure its validation. Under the optimized conditions—column temperature at 50 °C and flow rate at 0.25 mL/min—the three drugs, RC, GB, and CC, are separated. Their retention times are 0.840, 1.800, and 5.803 min, respectively. The assay was valid in terms of linearity, accuracy, and precision. Moreover, the developed assay shows a good tolerance against any change in the condition. The assay was tested also to separate the drugs in a pharmaceutical formulation as SNEDDs. The assay successfully separates the drug with a good resolution.

Low-frequency Raman spectroscopy (LFRS) is a valuable tool to detect the solid state of amorphous and crystalline drugs in solid dosage forms and the transformation of drugs between different polymorphic forms. It has also been applied to track the solubilisation of solid drugs as suspensions in milk and infant formula during in vitro digestion. This study reports the use of LFRS as an approach to probe drug precipitation from a lipid-based drug delivery system (medium-chain self-nanoemulsifying drug delivery system, MC-SNEDDS) during in vitro digestion. Upon lipolysis of the digestible components in MC-SNEDDS containing fenofibrate as a model drug, sharp phonon peaks appeared at the low-frequency Raman spectral region (<200 cm−1), indicating the precipitation of fenofibrate in a crystalline form from the formulation. Two multivariate data analysis approaches (principal component analysis and partial least squares discriminant analysis) and one univariate analysis approach (band ratios) were explored to track these spectral changes over time. The low-frequency Raman data produces results in good agreement with in situ small angle X-ray scattering (SAXS) measurements with all data analysis approaches used, whereas the mid-frequency Raman requires the use of PLS-DA to gain similar results. This suggests that LFRS can be used as a complementary, and potentially more accessible, technique to SAXS to determine the kinetics of drug precipitation from lipid-based formulations. [ABSTRACT FROM AUTHOR]

[Display omitted] • ・SNEDDS A composed of castor oil significantly improved oral absorption of clofazimine. • ・SNEDDS A provided the fine droplets under acidic, neutral and basic conditions. • ・Over 90% of clofazimine systemically absorbed would be via lymphatic transport. Clofazimine, an anti-leprosy drug, has been anticipated for a candidate to treat tuberculosis, cryptosporidiosis, and coronavirus infection, but its low oral bioavailability is considered a reason for its limited activity. In the current study, we have tried to improve the oral bioavailability of clofazimine by several SNEDDS formulations and characterized the absorption behavior from various aspects. Among four SNEDDS formulations prepared, SNEDDS A, prepared with castor oil as an oil component, provided the highest bioavailability (around 61%) and SNEDDS D, prepared with Capryol 90, gave the second highest bioavailability. SNEDDS A formed the finest nanoparticles, which were maintained under gastric and intestinal luminal conditions. The comparison in oral bioavailability between the SNEDDS formulation and its corresponding preformed nanoemulsion suggested that SNEDDS A would efficiently form nanoemulsion in the gastrointestinal tract after oral administration. AUC of mesenteric lymph node concentration was the highest for SNEDDS A, which would be one of the reasons for SNEDDS A to reveal the highest oral bioavailability. A cycloheximide-treated oral absorption study and single-pass perfusion study by utilizing a vascular–luminal perfused small intestine–liver preparation clearly indicated that over 90% of clofazimine absorbed to systemic circulation should be derived from lymphatic transport for both SNEDDS A and D. Furthermore, the fraction of dose absorbed was around 65% for SNEDDS D, but SNEDDS A achieved around 94%, indicating the excellent performance of SNEDDS A. [ABSTRACT FROM AUTHOR]

Piroxicam belongs to BCS class II and has low solubility. Self-nanoemulsifying drug delivery systems (SNEDDS) are considered a potential approach for increasing the solubility and release of piroxicam. This study aimed to select the components and component ratios of piroxicam SNEDDS using fractional factorial design 26-2 (FFD). The variables used in the DFT development of piroxicam SNEDDS are the type and concentration of oil (triacetin and oleic acid), surfactant (kolliphor EL and Tween 60), and co-surfactants (Transcutol and PEG 400). The FFD results showed 16 runs with different proportions of the piroxicam SNEDDS components, which were then characterized by critical parameters including emulsification time, %transmittance, droplet size, and drug loading. The components and component ratios of the PKM SNEDDS were determined using single-factor plot analysis. The results showed that triacetin (oil), kolliphor EL (surfactant), Transcutol (co-surfactant) had the greatest contribution to the formation of piroxicam SNEDDS with an oil ratio range of 11.11–28.57%, surfactant 44.44–77.78%, co-surfactant 11.11–44.44 %. [ABSTRACT FROM AUTHOR]

3D printing technology in medicine is gaining great attention from researchers since the FDA approved the first 3D-printed tablet (Spritam®) on the market. This technique permits the fabrication of various types of dosage forms with different geometries and designs. Its feasibility in the design of different types of pharmaceutical dosage forms is very promising for making quick prototypes because it is flexible and does not require expensive equipment or molds. However, the development of multi-functional drug delivery systems, specifically as solid dosage forms loaded with nanopharmaceuticals, has received attention in recent years, although it is challenging for formulators to convert them into a successful solid dosage form. The combination of nanotechnology with the 3D printing technique in the field of medicine has provided a platform to overcome the challenges associated with the fabrication of nanomedicine-based solid dosage forms. Therefore, the major focus of the present manuscript is to review the recent research developments that involved the formulation design of nanomedicine-based solid dosage forms utilizing 3D printing technology. Utilization of 3D printing techniques in the field of nanopharmaceuticals achieved the successful transformation of liquid polymeric nanocapsules and liquid self-nanoemulsifying drug delivery systems (SNEDDS) to solid dosage forms such as tablets and suppositories easily with customized doses as per the needs of the individual patient (personalized medicine). Furthermore, the present review also highlights the utility of extrusion-based 3D printing techniques (Pressure-Assisted Microsyringe—PAM; Fused Deposition Modeling—FDM) to produce tablets and suppositories containing polymeric nanocapsule systems and SNEDDS for oral and rectal administration. The manuscript critically analyzes contemporary research related to the impact of various process parameters on the performance of 3D-printed solid dosage forms. [ABSTRACT FROM AUTHOR]

High Performance Liquid Chromatography (HPLC) was used to determine vitamin D3 content from the topical dosage form. Self-nanoemulsifying drug delivery systems (SNEDDS) based hydrogel was aimed to optimize the delivery of vitamin D3 through the skin due to its high lipophilicity. Quantifying vitamin D3 was performed using the internal standard, vitamin D2, on LiChrocart C18 125-4 reverse phase column. Several characteristics of validation were referred including specificity, linearity, range, accuracy, precision, limits of detection, and quantification. The mobile phase was optimized as a mixture of acetonitrile-methanol-water for injection 94:3:3 v/v, and the flow rate was optimized at 0.8 mL/min at 25°C. Vitamin D3 detection and quantification were observed at a wavelength of 266 nm using an ultra-violet (UV) detector. The analysis method performed no excipient interference, including separating vitamin D3 from its matrix. Extraction of vitamin D3 from its matrix was observed using the dialysis membrane, with agitation (vortex) and no agitation (immersion). The drug content determination was found to be 108.22 % ± 14.77% for the immersion method and 72.04% ± 33.37% for the vortex method. Further, the high variability of the results indicated the dialysis membrane was not a suitable method for determining lipophilic drug content from the colloidal polymer matrix. The other techniques with negligible variation, such as reverse dialysis or subsequent solvent addition, are preferred. [ABSTRACT FROM AUTHOR]

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Kencur (Kaempferia galanga L.) rhizome ethanol extract contains a lipophilic compound of ethyl p-methoxycinnamate. Self-nanoemulsifying drug delivery system (SNEDDS) formulation can increase the solubility of the extract in water. The purpose of this study was to determine the effect of surfactant combination on the kencur rhizome extract in the SNEDDS system. The SNEDDS formulations were carried out by selecting the surfactant ratio of Tween 80:Span 80 and Tween 80:Chremophor RH 40, followed by selecting the ratio of surfactant mixtures to polyethylene glycol 400 as co-surfactant, and to virgin coconut oil as the oil phase. The clarity, transmittance, emulsification time, particle size, and polydispersity index were evaluated. The stability test was carried out in aquadest, artificial gastric fluid, and artificial intestinal fluid for 4 hours at 37°C. The results showed that the combination of Tween 80: Chremophor RH 40 produced better SNEDDS than Tween 80:Span 80. The combination of surfactant-cosurfactant of Tween 80:Chremophor RH 40:PEG 400 at ratio 3:1 and 1:1 could produce homogenous dispersed SNEDDS showing droplet size of 23,0 and 21,8 nm; transmittance of 95.63% and 93.83%, and SNEDDS preconcentrate emulsified less than 35 seconds. The single surfactant Tween 80:PEG 400 at the ratio 3:1 produce better dispersed SNEDDS than the combined surfactant with droplet size 16.3 nm, transmittance 97.85%, and SNEDDS preconcentrate emulsified less than 45 seconds. The SNEDDS system could produce a smaller droplet size than the extract in aquadest.

Single bulb garlic (SBG) has the potential as an immunomodulator; however, it has low solubility and bioavailability. A lipid-based delivery system, that is, the self-nanoemulsifying drug delivery system (SNEDDS), offers a novel opportunity in drug delivery. SBG can be a suitable candidate for SNEDDS development. This research aims to describe the physical stability, toxicity test of the SNEDDS, and SNEDDS SBG potential as antiinflammation in 3T3-L1 cells. The SNEDDS is made with various ratios of concentrations of carrier oil, surfactants, and cosurfactants, namely, 0.50: 3.45: 0.96, and added with SBG extract (SBGE) of 20 mg/mL. The results of the response test of SNEDDS SBGE formulation indicate an average and standard deviation of emulsification time of 16.38±3.01 (second), pH 7.21±0.08, and transmittance of 98.40±0.23(%). The average nanoemulsion size is 14.333±0.416 nm, polydispersion index of 0.213±0.056, and zeta potential of -14.67±0.72 mV. The results of the physical stability test indicate no segregation, deposition, cracking, or creaming in all nanoemulsion samples and SNEDDS SBG. The MTT test in a dose of 62.5, 125, 250, 500, 100, 2000, and 4000 µg/mL suggests that the highest viability of the 3T3-L1 cells is at a dose of 2000 µg/mL, which is 97.83%±1.55%. Therefore, SNEDDS SBGE can be a potential candidate for oral preparation by increasing bioavailability and reducing toxicity in the 3T3-L1 cells. An antiinflammatory test on the TNF-???? and IL-1???? expressions influences the 3T3-L1 cells. the SNEDDS of SBGE has the potential to reduce the expression of TNF-???? and IL-1???? and increase IL-10 expression in the methylglyoxal-induced 3T3-L1 cells.

Marsilea crenata C. Presl. contains phytoestrogens, which have structures or activity similar to estrogen and could potentially be utilized as a neuroprotector in an estrogen deficiency disease. This study aims to utilize M. crenata in the formulation of SNEDDS as a neuroprotector. The dosage form chosen aims to maintain stability and effectiveness because of its multi-compound properties. M. crenata was extracted using ethanol, then formulated into four SNEDDS formulas, and then characterization was done, which included physical quality (organoleptic and pH), particle size, polydispersity index, transmittance percentage, and Scanning Electron Microscope (SEM) analysis. The results showed that the four formulas produced a homogenous yellow color with a distinctive odor formulation; the values of the pH, particle size, polydispersity index, and transmittance percentage were still in the allowable range; and the SEM analysis showed that SNEDDS particles dominated with a spherical shape of particles. It can be concluded that the ethanol extract of M. crenata leaves can be formulated into SNEDDS and the best SNEDDS formulation was formula B at 100 ppm extract concentration which had the smallest particle size, smallest polydispersity index, and the largest transmission percentage. [ABSTRACT FROM AUTHOR]

Miconazole is a synthetic derivative of imidazole, a medication with a broad-spectrum antifungal agent that is used to treat localized vaginal, skin, and nail infections. The aim of the study was to develop an innovative technique to improve the permeability and efficacy of topical miconazole nitrate. A nanoemulgel of miconazole nitrate was formulated by the incorporation of a nanoemulsion and a hydrogel. The nanoemulsion was first optimized using a self-emulsifying technique, and the drug was then loaded into the optimum formulation and evaluated prior to mixing with the hydrogel. Miconazole nitrate nanoemulgel formulations were evaluated for their physical characteristics and antifungal activity. Based on the results, the formulation with 0.4 % Carbopol showed the highest release profile (41.8 mg/ml after 2 h); thus, it was chosen as the optimum formulation. A cell diffusion test was performed to examine the ability of the Miconazole nitrate nanoemulgel to penetrate the skin and reach the bloodstream. Percentage cumulative drug releases of 29.67 % and 23.79 % after 6 h were achieved for the MNZ nanoemulgel and the commercial cream, Daktazol, respectively. The antifungal activity of the novel MNZ nanoemulgel formulation was tested against Candida albicans and compared to Daktazol cream and almond oil; the results were: 40.9 ± 2.3 mm, 25.4 ± 2.7 mm and 18 ± 1.9 mm, respectively. In conclusion, a novel MNZ nanoemulgel showing superior antifungal activity compared to that of the commercial product has been developed. This nanotechnology technique is a step toward making pharmaceutical dosage forms that has a lot of promise. [ABSTRACT FROM AUTHOR]

Selection of super-saturable self-nano emulsion (S-SNE) component and further development to obtain the design space which met the requirements is very challenging. The purpose of this study was to develop pitavastatin S-SNE formulation through prior screening and selection followed by a simultaneous determination of the design space using an experimental design approach. The fractional factorial design 26-2 was successfully applied to screen appropriate compositions in S-SNE, namely oil, surfactant, and co-surfactant. Not only the types of S-SNE composition but also the range of concentration of each composition was achieved. The selected type and range of S-SNE composition was further developed using D-Optimal design to obtain the design space region, which had narrow and desirable features of S-SNE. Capryol 90, Tween 80, and Transcutol P were selected as S-SNE components. The simultaneous development of S-SNE formulation using an experimental design approach was successfully applied to formulate robust and controlled S-SNE characteristics. [ABSTRACT FROM AUTHOR]

Abiraterone acetate (ABRTA) is clinically beneficial in management of metastatic castration-resistant prostate cancer (PC-3). With highlighted low solubility and permeability, orally hampered treatment of ABRTA necessitate high dose to achieve therapeutic efficacy. To triumph these challenges, we aimed to develop intestinal lymphatic transport facilitating lipid-based delivery to enhance bioavailability. ABRTA-containing self-nano emulsified drug delivery (ABRTA-SNEDDS) was statistically optimized by D-optimal design using design expert. Optimized formulation was characterized for particle size, thermodynamic stability, in vitro release, in vivo bioavailability, intestinal lymphatic transport, in vitro cytotoxic effect, anti-metastatic activity, and apoptosis study. Moreover, hemolysis and histopathology studies have been performed to assess pre-clinical safety. Nano-sized particles and successful saturated drug loading were obtained for optimized formulation. In vitro release upto 98.61 ± 3.20% reveal effective release of formulation at intestinal pH 6.8. ABRTA-SNEDDS formulation shows enhanced in vivo exposure of Abiraterone (2.5-fold) than ABRTA suspension in Sprague–Dawley rats. In vitro efficacy in PC-3 cell line indicates 3.69-fold higher therapeutic potential of nano drug delivery system. Hemolysis and histopathology study indicates no significant toxicities to red blood cells and tissues, respectively. Apparently, an opportunistic strategy to increasing bioavailability of ABRTA via intestinal lymphatic transport will create a viable platform in rapidly evolving chemotherapy. Enhanced translational utility of delivery was also supported through in vitro therapeutic efficacy and safety assessments. Abiraterone acetate is a prostate cancer drug, impeded with low bioavailability. ABRTA loaded in self nano emulsifying drug delivery enhanced its bioavailability. Intestinal lymphatic transport played role in enhanced bioavailability of ABRTA. ABRTA-SNEDDS enhanced in vitro cytotoxic activity of ABRTA. ABRTA-SNEDDS found safe in preclinical safety evaluations [ABSTRACT FROM AUTHOR]

Disodium pamidronate, a second-generation bisphosphonate is a potent drug for the treatment of osteoporosis, which has been very well established by previous literature. It has very low oral permeability, leading to its low oral bioavailability, which restrict this drug to being administered orally. Therefore, the present research work includes the development of an orally effective nanoformulation of pamidronate. In this work, disodium pamidronate was complexed with phospholipon 90G for the enhancement of permeability and to investigate the phospholipon 90G–tagged pamidronate complex–loaded SNEDDS for oral delivery with promises of enhanced bioavailability and anti-osteoporotic activity. The rational design and optimization was employed using Central Composite Design (Design Expert® 12, software) to optimize nanoformulation parameters. In this work, a commercially potential self nano-emulsifying drug delivery system (SNEDDS) has been developed and evaluated for improved oral bioavailability and better clinical acceptance. The hot micro-emulsification and ultracentrifugation method with vortex mixing was utilized for effective tagging of phospholipon 90G with pamidronate and then loading into the SNEDDS nanocarrier. The optimized Pam-PLc SNEDDS formulation was characterized for particle size, PDI, and zeta potential and found to be 56.38 ± 1.37 nm, 0.218 ± 0.113, and 22.41 ± 1.14 respectively. Also, a 37.9% improved bioavailability of pamidronate compared to marketed tablet was observed. Similarly, in vivo pharmacokinetic studies suggest a 31.77% increased bone density and significant enhanced bone biomarkers compared to marketed tablets. The developed formulation is safe and effectively overcomes anti-osteoporosis promises with improved therapeutic potential. This work provides very significant achievements in postmenopausal osteoporosis treatment and may lead to possible use of nanotherapeutic-driven emerging biodegradable carriers-based drug delivery. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated that Sirtuin-1 (SIRT-1)-activating molecules exert a protective role in degenerative ocular diseases. However, these molecules hardly reach the back of the eye due to poor solubility in aqueous environments and low bioavailability after topical application on the eye’s surface. Such hindrances, combined with stability issues, call for the need for innovative delivery strategies. Within this context, the development of self-nanoemulsifying drug delivery systems (SNEDDS) for SIRT-1 delivery can represent a promising approach. The aim of the work was to design and optimize SNEDDS for the ocular delivery of two natural SIRT-1 agonists, resveratrol (RSV) and melatonin (MEL), with potential implications for treating diabetic retinopathy. Pre-formulation studies were performed by a Design of Experiment (DoE) approach to construct the ternary phase diagram. The optimization phase was carried out using Response Surface Methodology (RSM). Four types of SNEDDS consisting of different surfactants (Tween® 80, Tween® 20, Solutol® HS15, and Cremophor® EL) were optimized to achieve the best physico-chemical parameters for ocular application. Stability tests indicated that SNEDDS produced with Tween® 80 was the formulation that best preserved the stability of molecules, and so it was, therefore, selected for further technological studies. The optimized formulation was prepared with Capryol® PGMC, Tween® 80, and Transcutol® P and loaded with RSV or MEL. The SNEDDS were evaluated for other parameters, such as the mean size (found to be ˂50 nm), size homogeneity (PDI < 0.2), emulsion time (around 40 s), transparency, drug content (>90%), mucoadhesion strength, in vitro drug release, pH and osmolarity, stability to dilution, and cloud point. Finally, an in vitro evaluation was performed on a rabbit corneal epithelial cell line (SIRC) to assess their cytocompatibility. The overall results suggest that SNEDDS can be used as promising nanocarriers for the ocular drug delivery of RSV and MEL.

SNEDDS were developed with the objective of treating low bioavailability of drugs for antiviral drugs due to its low solubility. The scientist has increased their interest in improving bioavailability and absorption of poorly-water soluble drugs using Self-Emulsifying lipid technology. SNEDDS was an isocratic mixture contains an Oil, Surfactant, Co-surfactant, and Drug in accurate amount. The SNEDDS was primarily prepared as liquid-SNEDDS, but S-SNEDDS was more stable as compared to L-SNEDDS. As viral infection was major threat for people due to its limited efficacy and Serious adverse effects. The most damaging viral diseases was treated with help of SNEDDS as delivery system. They were a leading cause of morbidity and mortality. The plant and plant source were major source from which the extracted metabolites used for synthesis of drug through metabolic pathway. The phytochemicals and extracts were better and safe alternative for synthetic drugs. The phytochemicals like Curcumin, Myricetin, Apigenin etc. used as drug for treating antivirals using SNEDDS. This technique was used for quantitative and qualitative analysis. Also, the ternary phase diagram gives dramatic representation of Oil, surfactant and Co-surfactant which shows its concentration. Some characterization techniques were Droplet size, Zeta potential, XRD, DSC, FTIR, and TGA. Also, QbD provides a platform for systemic production of drug formulations. QbD was used for its better bioavailability.

Thymoquinone (TMQ), present in Nigella sativa L., exhibits antioxidant, anti-inflammatory, and anti-apoptotic properties. Poor aqueous solubility, low oral bioavailability, hepatic first-pass metabolic constraints, and pH instability have limited TMQ’s in vivo use in clinical settings. This study designed and prepared thermodynamically stable, self-emulsified, nanoscale vesicles with the ternary diagram assistance to produce self-nanoemulsifying drug delivery system (SNEDDS). The TMQ-SNEDDS preparations used clove oil, isopropyl myristate (IPM) (1:1), Labrasol, and Transcutol-P. The SNEDDS mean droplet size varied between 72.85 and 98.42 nm, and approximately >70% TMQ was released within the first 4 h. The peak plasma concentration values of TMQSNE3 and TMQ suspension were 420.31 ± 35.23 and 98.51 ± 9.97 μg/mL, respectively, whereas time to achieve the peak plasma concentration values were 0.75 ± 0.12 and 1.0 ± 0.30 h, respectively. The area under the curve from time 0 to t (AUC0–t ) and the area under the moment curve from time 0 to t (AUMC0–t ) of TMQSNE3 were found to be 1838.63 ± 55.73 µg h/mL and 1909.59 ± 382.81 µg h/mL, respectively, which were highly significant (p < 0.05) in comparison with AUC0–t (389.36 ± 87.08 μg h/mL) and AUMC0–t (390.31 ± 184.55 μg h/mL) of the TMQ suspension. The relative bioavailability of TMQ was enhanced by 4.7-folds for the optimized TMQSNEDDS than that of the free drug suspension. The SNEDDS enhanced the bioavailability, which, in turn, positively affected the therapeutic efficacy of this naturally bioactive compound, TMQ, which has delivery and bioavailability problems owing to poor aqueous solubility.

Ipomoea reptans Poir has many health benefits, such as decreasing blood glucose and as an antioxidant. Self-nano emulsifying drug delivery systems (SNEDDS) are an innovation in pharmaceutical technology that minimizes drug molecules and maximizes surface area, thus increasing drug absorption. This study was aimed to investigate SNEDDS of I. reptans acute toxicity on female Wistar rats. An acute toxicity test was done using a limit test of OECD 423. Female Wistar rats were divided into two groups, control and treatment group, with 3 animals for each group were used per step. There are no animals that died after were given SNEDDS of I. reptans leaves extract at a dose of 2000 mg/kg. No toxic effect was detected at clinical examination and histopathology of the organ. SNEDDS of I. reptans leaves extract has an LD50 cut-off value of 5000 mg/kg.