Nanoemulsifying Drug Delivery System Research Articles

Optimization and Characterization of Self Nano Emulsifying Drug Delivery System loaded with 18- β Glycerrhetinic acid

The purpose of this study was to prepare, optimize and evaluate self nano emulsifying drug delivery system (SNEDDS) containing 18- β glycerrhetinic acid which enhances the dissolution profile or bioavailability of the drug in comparison to pure suspension of 18- β glycerrhetinic acid.18- β glycerrhetinic acid loaded SNEDDS having geranium oil as oil phase, tween 80 as a surfactant, and dimethyl sulfoxide (DMSO) as co-surfactant were prepared using pseudo ternary phase diagram and Box-Behnken experimental design was used to optimize the different formulations. Optimized formulations were characterized for self-emulsifying time, globule size, zeta potential, and drug release. The mean droplet size and PDI of the optimized formulation were found to be in a variation of 93.42 nm and 0.401 respectively. FTIR data showed no physicochemical interaction between excipients and drug. The encapsulation efficiency of optimised 18- β glycerrhetinic acid SNEDDS was found 80.12±1.52% , % transmittance was found 99.34±0.134% and the viscosity of all the formulations was found 0.8872 cp. Three-dimensional response surface plots and two-dimensional contour plots of the responses across the selected factors were constructed that explained the relationship between the independent and dependent variables. Release kinetics was calculated by using KinetDS3.0. It was concluded that prepared formulations were formulated with approximately desired mean droplet size confirmed by Box- Behnken experimental design as well as properly optimized and characterized.

Formulation and Evaluation of Solid Self Nano Emulsifying drug delivery System of Olanzapine to Enhance Aqueous Solubility and Dissolution Rate

Present research work was aimed to enhance aqueous solubility and dissolution rate of olanzapine by solid self nano emulsifying drug delivery system(S-SNEDDS). Olanzapine is a BCS class II drug having 65% oral bioavailability; it is used in the treatment of psychosis, depression and mania conditions. Oils, Surfactants, Co surfactants were selected depending upon the saturated solubility of olanzapine in those components; excipients were screened depending on olanzapine solubility in various oils, surfactants and co surfactants. Surfactant: co surfactant {Smix} ratios i.e., 3:1 and 4:1 were prepared to determine nano emulsion regions and also to formulate liquid self nano emulsifying drug delivery system (L-SNEDDS). Pseudo ternary phase diagram were plotted by using Triplot version 4.1.2 software, nano emulsion region was determined and evaluated. Formulations were designed based on saturated solubility of olanzapine and Pseudo ternary phase diagram using various ratios of oils [Capryol 90], surfactants [Kolliphor EL], co surfactants [Lauroglycol 90] depending on its solubility and nano emulsion formation four formulations were developed which are further selected for characterisation of L-SNEDDS like robustness to dilution, self emulsification, determination of droplet size, PDI, Drug loading efficacy, zeta potential and also Invitro drug release. Among those four formulations, F1 (SB184J 4:6) was optimum because compared to other three formulations F3 gave best results in terms of droplet size (66nm) with PDI (0.24), Invitro drug release, dissolution rate of F1 SNEDDS having (88.201± 0.25%). Invitro drug release of F1 formulation was compared with that of Olanzapine [API] (45.281± 0.52%) the results indicating that there is a increase in solubility and dissolution rate of olanzapine by 2.2 times more compared to pure olanzapine (API). F1 (SB184J 4:6) were converted into S-SNEDDS by adsorption process by addition porous carriers (Aerosil 200). Formulated S-SNEDDS were undergone various evaluation parameters and also reconstitution parameters to determine Droplet size and Invitro drug release of solid F1 (SB184J4:6) formulation. The results of present study demonstrates that olanzapine SNEDDS has an ability and potential to enhance solubility and dissolution rate.

SELF NANO-EMULSIFYING DRUG DELIVERY SYSTEM: A REVIEW

Developments in recent drug discovery programs, yields a large proportion of novel pharmacologically active molecules that are lipophilic and poorly soluble, which is a major challenge for pharmaceutical researchers to enhance the oral bioavailability of such drug molecules. The self-nanoemulsifying drug delivery system (SNEDDS) is a promising Drug Delivery System which is well known for its prospective to improve the aqueous solubility and oral absorption of poorly water soluble drugs. SNEDDS is an isotropic mixture comprising oil, surfactant, co-surfactant and drug that form oil in water emulsion in aqueous environment under placid agitation. It can readily disperse in the aqueous environment of the gastrointestinal tract to form a fine oil-in-water emulsion with a droplet size not exceeding 100 nm under mild agitation for improving the oral bioavailability of poorly water-soluble drugs. The self nano-emulsifying Drug Delivery System (SNEDDS) is applicable on BCS Class II and Class IV Drugs for improving water Solubility of poorly water soluble drugs. It is the novel drug delivery system which is applicable for oral, parenteral, ophthalmic, intranasal and cosmetic delivery of drugs. The review presents an overview of design of formulation, preparation of components, mechanism of selfemulsification, biopharmaceutical aspects and evaluation of self nano-emulsifying drug delivery system (SNEDDS) for enhancement of oral bioavailability of poorly water soluble drugs.

In Vitro Evaluation of a Solid Supersaturated Self Nanoemulsifying Drug Delivery System (Super-SNEDDS) of Aprepitant for Enhanced Solubility.

Aprepitant (APR) belongs to Class II of the Biopharmaceutical Classification System (BCS) because of its low aqueous solubility. The objective of the current work is to develop self-nanoemulsifying drug delivery systems (SNEDDS) of APR to enhance its aqueous solubility. Preformulation studies involving screening of excipients for solubility and emulsification efficiency were carried out. Pseudo ternary phase diagrams were constructed with blends of oil (Imwitor® 988), cosolvent (Transcutol® P), and various surfactants (Kolliphor® RH40, Kolliphor® ELP, Kolliphor® HS15). The prepared SNEDDS were characterized for droplet size and nanoemulsion stability after dilution. Supersaturated SNEDDS (super-SNEDDS) were prepared to increase the quantity of loaded APR into the formulations. HPMC, PVP, PVP/VA, and Soluplus® were used as polymeric precipitation inhibitors (PPI). PPIs were added to the formulations at 5% and 10% by weight. The influence of the PPIs on drug precipitation was investigated. In vitro lipolysis test was carried out to simulate digestion of formulations in the gastrointestinal tract. Optimized super-SNEDDS were formulated into free-flowing granules by adsorption on the porous carriers such as Neusilin® US2. In vitro dissolution studies of solid super-SNEDDS formulation revealed an increased dissolution rate of the drug due to enhanced solubility. Consequently, a formulation to improve the solubility and potentially bioavailability of the drug was developed.

Stability Study of Super Saturable Catechin-Self Nano Emulsifying Drug Delivery System as Antidiabetic Therapy

Diabetes mellitus is a metabolic syndrome characterized by hyperglycemic and increased ROS production, which causes oxidative stress. Catechin isolated from the tea plant has oxidative stress inhibitor activity and anti-diabetic activity with low absorption in circulation systemic. Therefore, it is formulated in a super saturable catechin-self nano emulsifying drug delivery system (SSC-SNEDDS). Stability is one of the factors that affect the safety, quality, and efficacy of SSC-SNEDDS. This study aims to evaluate the stability of the formulated oil phase using oleic acid, croduret as a surfactant, and propylene glycol as a co-surfactant. Stability studies were carried out by several tests, namely heating-cooling cycle assay, freeze-thaw cycle assay, centrifugation, and endurance assay. Droplet characterization in the form of changes in diameter, zeta potential, and mobility in evaluating stability tests using dynamic light scattering-particle size analyzer (DLS-PSA). Real-time stability was also evaluated by observing changes in the infrared spectrum pattern using FTIR-ATR. After the stability test, the emulsion droplet size of SSC-SNEDDS was still below 100 nm and showed good stability. It can be concluded that the formula has a good stability profile.

Lipid-based emulsion drug delivery systems - a comprehensive review.

Lipid-based emulsion system - a subcategory of emulsion technology, has emerged as an enticing option to improve the solubility of the steadily rising water-insoluble candidates. Along with enhancing solubility, additional advantages such as improvement in permeability, protection against pre-systemic metabolism, ease of manufacturing, and easy to scale-up have made lipid-based emulsion technology very popular among academicians and manufacturers. The present article provides a comprehensive review regarding various critical properties of lipid-based emulsion systems, such as microemulsion, nanoemulsion, SMEDDS (self microemulsifying drug delivery system), and SNEDDS (self nanoemulsifying drug delivery system). The present article also explains in detail the similarities and differences between them, the stabilization mechanism, methods of preparation, excipients used to prepare them, and evaluation techniques. Subtle differences between nearly related terminologies such as microemulsion and nanoemulsion, SMEDDS, and SNEDDS are also explained in detail to clarify the basic differences. The present article also gives in-depth information regarding the chemical structure of various lipidic excipients, various possible chemical modifications to modify their inherent properties, and their regulatory status for rational selection.

A Literature Review on Self Nanoemulsifying Drug Delivery System (SNEDDS)

The Lipid-based drug delivery system is extensively reported within the literature for the enhancing drug solubility, permeability, and bioavailability. A considerable majority of novel pharmacologically active constituents produced in recent drug discovery programs are lipophilic and poorly soluble, posing a significant problem for pharmaceutical researchers enhancing the oral bioavailability of such drug molecules. Self-nano emulsifying drug delivery systems (SNEDDS), are the viable oil-based approaches for drugs that exhibit low dissolution rate and inadequate absorption. Ever since the progress of SNEDDS, researchers have been focusing on the challenges of BCS Class II and Class IV Drugs for enhancing water Solubility of poorly water-soluble drugs. SNEDDS is a Validate method for enhancing the solubility and bioavailability of lipophilic compounds. It’s the isotropic mixture of oil, surfactant, co-surfactant molecules and it also containing co-solvent molecule. which spontaneously form oil-in-water nano emulsion of approximately 200 nm or less in size upon dilution with water under gentle stirring. It’s Drug delivery system Which possess thermodynamically and kinetically stability. The physicochemical properties, drug solubilization capacity considerably regulates the selection of the SNEDDS components. The compositions of the SNEDDS are often optimized with the assistance of phase diagrams. Further to optimize SNEDDS can be done with the help of statistical experimental design. It’s a Novel drug delivery system which is applicable for the parenteral, Ophthalmic, intranasal and cosmetic drug delivery system. And therefore, the present review describes Preparation, components, mechanism of self-Nano emulsification, biopharmaceutical aspects, characterization methods and applications of Selfnanoemulsifying drug delivery system (SNEDDS).

Solid self nano-emulsifying system for the enhancement of dissolution and bioavailability of Prasugrel HCl: in vitro and in vivo studies

Prasugrel Hydrochloride (PHCl) is an antiplatelet drug. It is a class II drug with variable bioavailability. The objective of this work was to enhance the solubility and hence the bioavailability and efficacy of PHCl. A Self Nano-Emulsifying Drug Delivery System (SNEDDS) was prepared using Kolliphor El, Maisine 35-1, and Transcutol P as surfactant, oil, and co-surfactant, respectively in a ratio 10:72:18 v/v%. The SNEDDS was converted into solid by adsorption onto Neusilin. In vitro release of the drug from SNEDDS in (pH = 4) at 37 °C and 75 rpm for 45 min was studied. The results were compared to those from the unprocessed PHCl and Lexar® (the commercial drug). In-vivo studies (platelet Aggregation and bleeding time) were conducted using rats as animal models. It was found that the particle size of the SNEDDS ranged between 80 and 155 nm and EE% was in the range of 90.2% ± 0.4. The release from SNEDDS was about 84% compared to around 25% from unprocessed PHCl and 65% from Lexar® after 15 min. The platelet aggregation of the formula was lower than the PHCl, and Lexar® indicating higher bioavailability. In conclusion, SNEDDS with high EE% was prepared and was successful in enhancing the solubility, dissolution rate, and the bioavailability.

Development of mushroom polysaccharide and probiotics based solid self-nanoemulsifying drug delivery system loaded with curcumin and quercetin to improve their dissolution rate and permeability: State of the art

The role of mushroom polysaccharides and probiotics as pharmaceutical excipients for development of nanocarriers has never been explored. In the present study an attempt has been made to explore Ganoderma lucidum extract powder (GLEP) containing polysaccharides and probiotics to convert liquid self nanoemulsifying drug delivery system (SNEDDS) into solid free flowing powder. Two lipophilic drugs, curcumin and quercetin were used in this study due to their dissolution rate limited oral bioavailability and poor permeability. These were loaded into liquid SNEDDS by dissolving them into isotropic mixture of Labrafill M1944CS, Capmul MCM, Tween-80 and Transcutol P. The liquid SNEDDS were solidified using probiotics and mushroom polysaccharides as carriers and Aerosil-200 as coating agent. The solidification was carried out using spray drying process. The process and formulation variables for spray drying process of liquid SNEDDS were optimized using Box Behnken Design to attain required powder properties. The release of both drugs from the optimized spray dried (SD) formulation was found to be more than 90%, whereas, it was less than 20% for unprocessed drugs. The results of DSC, PXRD and SEM, showed that the developed L-SNEDDS preconcentrate was successfully loaded onto the porous surface of probiotics, mushroom polysaccharides and Aerosil-200.

Ion-Triggered In Situ Gelling Nanoemulgel as a Platform for Nose-to-Brain Delivery of Small Lipophilic Molecules.

Background: Intranasal route offers a direct nose-to-brain delivery via olfactory and trigeminal nerves and minimizes the systemic exposure of the drug. Although reliable and non-invasive, intranasal administration of lipophilic neuroprotective agents for brain targeting is still challenging. Literature focuses on naturally-derived compounds as a promising therapeutics for chronic brain diseases. Naringin, a natural flavonoid obtained from citrus fruits possesses neuroprotective effects. By regulating multiple crucial cellular signaling pathways, naringin acts on several therapeutic targets that make it suitable for the treatment of neurodegenerative diseases like Alzheimer’s disease and making it a suitable candidate for nasal administration. However, the hydrophobicity of naringin is the primary challenge to formulate it in an aqueous system for nasal administration. Method: We designed a lipid-based nanoemulsifying drug delivery system of naringin using Acrysol K140 as an oil, Tween 80 as a surfactant and Transcutol HP as a cosolvent, to improve solubility and harness the benefits of nanosizing like improved cellular penetration. Intranasal instillations of therapeutic agents have limited efficacy due to drug washout and inadequate adherence to the nasal mucosa. Therefore, we reconstituted the naringin self-emulsifying system in a smart, biodegradable, ion-triggered in situ gelling hydrogel and optimized for desirable gel characteristics. The naringin-loaded composition was optimized and characterized for various physicochemical and rheological properties. Results: The formulation showed a mean droplet size 152.03 ± 4.6 nm with a polydispersity index <0.23. Ex vivo transmucosal permeation kinetics of the developed formulation through sheep nasal mucosa showed sustained diffusion and enhanced steady-state flux and permeability coefficient. Scanning and transmission electron microscopy revealed the spherical shape of emulsion droplets and entrapment of droplets in a gel structure. The formulation showed excellent biocompatibility as analyzed from the viability of L929 fibroblast cells and nasal mucosa histopathology after treatment. In vivo biodistribution studies revealed significantly higher drug transport and brain targeting efficiency. Conclusion: In situ gelling system with nanoemulsified naringin demonstrated a safe nasal delivery providing a new dimension to the treatment of chronic neurodegenerative diseases using small hydrophobic phytoconstituents with minimization of dose and related systemic adverse effects.

Colloidal and vesicular delivery system for herbal bioactive constituents.

The main objective of the present review is to explore and examine the effectiveness of currently developed novel techniques to resolve the issues which are associated with the herbal constituents/extract. A systematic thorough search and collection of reviewed information from Science direct, PubMed and Google Scholar databases based on various sets of key phrases have been performed. All the findings from these data have been studied and briefed based on their relevant and irrelevant information. Herbal drugs are gaining more popularity in the modern world due to their applications in curing various ailments with minimum toxic effects, side effect or adverse effect. However, various challenges exist with herbal extracts/plant actives such as poor solubility (water/lipid), poor permeation, lack of targeting specificity, instability in highly acidic pH, and liver metabolism, etc. Nowadays with the expansion in the technology, novel drug delivery system provides avenues and newer opportunity towards the delivery of herbal drugs with improved physical chemical properties, pharmacokinetic and pharmacodynamic. Developing nano-strategies like Polymeric nanoparticles, Liposomes, Niosomes, Microspheres, Phytosomes, Nanoemulsion and Self Nano Emulsifying Drug Delivery System, etc. imparts benefits for delivery of phyto formulation and herbal bioactives. Nano formulation of phytoconstituents/ herbal extract could lead to enhancement of aqueous solubility, dissolution, bioavailability, stability, reduce toxicity, permeation, sustained delivery, protection from enzymatic degradation, etc. CONCLUSION: Based on the above findings, the conclusion can be drawn that the nano sized novel drug delivery systems of herbal and herbal bioactives have a potential future for upgrading the pharmacological action and defeating or overcoming the issues related with these constituents. The aims of the present review was to summarize and critically analyze the recent development of nano sized strategies for promising phytochemicals delivery systems along with their therapeutic applications supported by experimental evidence and discussing the opportunities for further aspects.

Formulation and Evaluation of Self Nano Emulsifying Drug Delivery System of Raloxifene Hydrochloride

Raloxifene hydrochloride (RLX) is a selective Estrogen-receptor modulator used to treat osteoporosis as well as breast and endometrial cancer prevention. The bioavailability of RLX is only 2% due to substantial pre-systemic clearance. The goal of this research was to customise and characterise RLX-loaded self-nanoemulsifying drug-delivery systems (SNEDDS) by using bioactive excipients that impact drug metabolism. The droplet size, zeta potential and drug content determination of optimized formulation (F-06) was found to be 147.5 nm, -28.8, 99.67% respectively. The drug release study from the nano formulation was studied in Phosphate buffer 6.8 for all the formulations F1,F2,F3,F4,F5,F6 and F7. The optimized formulation was found to be F6&#x0D; Keywords: Raloxifene hydrochloride, nanoemulsion, SNEDDS

A Review on Formulation and Development of Solid Self-Nano Emulsifying Drug Delivery Systems

This article describes current strategies to enhance aqueous solubility and dissolution rate of poor soluble drugs. Most drugs in the market are lipophilic with low or poor water solubility. There are various methods to enhance solubility: co-solvency, particle size reduction, salt formation and Self Nanoemulsifying drug delivery systems, SEDDS is a novel approach to enhance solubility, dissolution rate and bioavailability of drugs. The study involves formulation and evaluation of solid self-Nano emulsifying drug delivery system (S-SNEDDS) to enhance aqueous solubility and dissolution rate. Oral route is the most convenient route for non-invasive administration. S-SNEDDS has more advantages when compared to the liquid self-emulsifying drug delivery system. Excipients were selected depends upon the drug compatibility oils, surfactants and co surfactants were selected to formulate Liquid SNEDDS these formulated liquid self-nano emulsifying drug delivery system converted into solid by the help of porous carriers, Melted binder or with the help of drying process. Conversion process of liquid to solid involves various techniques; they are spray drying; freeze drying and fluid bed coating technique; extrusion, melting granulation technique. Liquid SNEDDS has a high ability to improve dissolution and solubility of drugs but it also has disadvantages like incompatibility, decreased drug loading, shorter shelf life, ease of manufacturing and ability to deliver peptides that are prone to enzymatic hydrolysis.&#x0D;

Novel Self-Nano-Emulsifying Drug Delivery Systems Containing Astaxanthin for Topical Skin Delivery

Astaxanthin (ASX) is a potent lipophilic antioxidant derived from the natural pigment that gives marine animals their distinctive red-orange colour and confers protection from ultraviolet radiation. Self nano-emulsifying drug delivery systems (SNEDDS) have been successfully developed and evaluated to increase the skin penetration of ASX and target its antioxidant and anti-inflammatory potential to the epidermis and dermis. SNEDDS were prepared using a low-temperature spontaneous emulsification method, and their physical characteristics, stability, antioxidant activity, and skin penetration were characterized. Terpenes (D-limonene, geraniol, and farnesol) were included in the SNEDDS formulations to evaluate their potential skin penetration enhancement. An HPLC assay was developed that allowed ASX recovery from skin tissues and quantification. All SNEDDS formulations had droplets in the 20 nm range, with low polydispersity. ASX stability over 28 days storage in light and dark conditions was improved and antioxidant activity was high. SNEDDS-L1 (no terpene) gave significantly increased ASX penetration to the stratum corneum (SC) and the epidermis-dermis-follicle region (E + D + F) compared to an ASX in oil solution and a commercial ASX facial serum product. The SNEDDS-containing D-limonene gave the highest ASX permeation enhancement, with 3.34- and 3.79-fold the amount in the SC and E + D + F, respectively, compared to a similar applied dose of ASX in oil. We concluded that SNEDDS provide an effective formulation strategy for enhanced skin penetration of a highly lipophilic molecule, and when applied to ASX, have the potential to provide topical formulations for UV protection, anti-aging, and inflammatory conditions of the skin.

Improvement of the bioavailability of curcumin by a supersaturatable self nanoemulsifying drug delivery system with incorporation of a hydrophilic polymer: in vitro and in vivo characterisation.

The current study was focused on preparing curcumin (CUR) supersaturated self-nano-emulsion (PI-CUR-SNEDDS) using hydrophilic polymer and to study the influence of polymer precipitation inhibitor on the physicochemical and biopharmaceutical properties of the PI-CUR-SNEDDS. PI-CUR-SNEDDS were prepared using hydrophilic polymer in order to maintain the supersaturation of CUR in nano-emulsion solution, artificial gastrointestinal fluid (AGF), and the precipitates formed, and characterised by in vitro dispersion tests, in vitro intestinal absorption and in vivo pharmacokinetic and compared with CUR-SNEDDS. PI-CUR-SNEDDS prepared with 2% hydroxypropyl methylcellulose 55-60 (HPMC55-60) as precipitation inhibitor (PI) significantly improved the viscosity, physical stability and CUR's equilibrium solubility of nanoemulsion. HPMC55-60 and CUR interact in AGF through intermolecular interactions, form hydrogen bonds, and produce amorphous precipitates. Compared with CUR-SNEDDS, the proportion of CUR in the hydrophilic phase increased by about 3-fold, and apparent permeability coefficient (Papp) in duodenum, jejunum, ileum, and colon increased by 2.30, 3.65, 1.54 and 2.08-fold, respectively, and the area under the plasma concentration-time curve0-12h of PI-CUR-SNEDDS also increased by 3.50-fold. Our results suggested that HPMC55-60 maintained the CUR supersaturation state by forming hydrogen bonds with CUR, increasing the solution's viscosity and drug solubilisation, thus improving the absorption and bioavailability of CUR.

SNEDDS Formulation of Black Cumin Seed Oil using Tween 80 and Sorbitol as a Surfactant and Cosurfactant

Black cumin seed oil has many benefits. One of which is as an anticancer, it can be used as an opportunity to develop drugs that utilizes the black cumin seed oil. A method to improve the stability and absorption of the drug in the body is within the formulation of Self Nano Emulsifying Drug Delivery System (SNEDDS). This study aims to determine whether the black cumin seed oil can be made into SNEDDS formula with tween 80 and sorbitol as a surfactant and cosurfactant along with the establishment for the optimal formula. SNEDDS formula of black cumin seed oil was optimized using SLD method by DX.10 software. SNEDDS formula was made using tween 80 as surfactant and sorbitol as cosurfactant. Previously carried out with the manufacturing of a trial formula to determine the lower and upper value of each component, then 14 formulas were made based on DX.10. The formula were evaluated for transmittance percentage in 650 nm wavelength and emulsification time of 37oC. Results of the tests included in DX10 is to obtain the optimal formula. The optimal formula was validated by t-test and evaluated for droplet size, zeta potential, and stability test of nanoemulsion in artificial gastric fluid (AGF) and artificial intestinal fluid (AIF) for 4 hours. The results showed that the proportion of 13% black cumin seed oil, 60% tween 80 and 27% sorbitol is able to establish the optimal SNEDDS formula of black cumin seed oil. Transmittan value of the optimal formula was 92% with the emulsification time of 56 seconds, SNEDDS black cumin seed oil droplet size of 21.5 nm, zeta potential value -31.5 mV and nanoemulsion stable in the AIF and AGF.

Preparation and Characterization of Novel Self Nano Emulsifying Drug Delivery System of Allopurinol

The aim of research was to develop self nanoemulsifying drug delivery technology containing low aqueous soluble drug allopurinol for improving solubility, dissolution and bioavaibility. Preliminary screening were carried on the basis of maximum solubility of allopurinol in oil, surfactant, co-surfactant and pseudo-ternary phase diagram was constructed to identify the ratio of surfactant and co-surfactant for nanoemulsion formulation using water titration method. Based on the solubility study, Labrafil M 1944 CS, Cremophor RH 40, Transcutol used as oil, surfactant, and co-surfactant respectively. Pseudo-ternary phase diagram was constructed to identify the ratio of surfactant and co-surfactant for nanoemulsion formation by water titration method. As per the ternary phase diagram ratio of Smix in 2:1 was identified with maximum emulsification area. SNEDDS composed of 35 % Labrafil M 1944 CS, 43.34% Cremophor RH 40, 21.66% Transcutol. Globule size was found to be 25.42 nm, and zeta potential value was -9.26 mV. Prepared SNEDDS were evaluated for globule size, viscosity, emulsification time, cloud point, dilution test and thermodynamic stability study. Prepared liquid SNEDDS then converted into solid SNEDDS via extrusion/spheronization technique using Aerosil 200, lactose monohydrate and Croscarmellose sodium. The pellets containing SNEDDS possessed good flow properties and mechanical strength and other rheological parameters. Self nanoemulsifying pellet exhibited uniform size and shape. Friability, dissolution time and disintegration of pellets formulation shown promising results. Time required for 80% drug release of self nanoemulsifying pellet was found to be 26 min, which was significantly lower than liquid SNEDDS, plain drug containing pellet and marketed preparation of Allopurinol (ZYRIK).

Formulation and Evaluation of α-Pinene Loaded Self-emulsifying Nanoformulation for In-Vivo Anti-Parkinson's Activity.

The present study was aimed to developed and optimize the self-nano emulsifying drug delivery system of α-pinene (ALP-SNEDDS) and evaluate its in-vivo anti-Parkinson's activity. Different lipid-based drug delivery technologies have been researched to upgrade drug bioavailability and expand their clinical adequacy upon oral administration. Self-emulsifying drug delivery systems (SEDDS) have pulled in developing the interest specifically for self nano emulsifying drug delivery systems (SNEDDS). The present work was attempted to improve the bioavailability of the ALP by defining the role of self-nano emulsifying formulations for its neuroprotective effect. Miscibility of the ALP was estimated in various excipient components to select the optimized combination. Self-nano emulsification, thermodynamic stability, the effect of dilution on robustness, optical clarity, viscosity, and conductivity tests were performed. The in-vivo anti-Parkinson's activity of the ALP-SNEDDS formulations were done using Pilocarpine antagonism induced Parkinsonism in rodents. Behavioral tests like tremulous jaw movements, body temperature, salivation, and lacrimation are performed. Two optimized formulations, composed of Anise oil, Tween 80, and Transcutol-HP of Oil: Smix ratio (4:6 and 3:7) were selected. The Smix ratio for both the formulation was 2:1. The particle size was found to consistent with the increase in dilution. The mean negative zeta potential of the formulations was found to be increased with an increase in dilution. The TEM images of the formulations revealed spherical shape of the droplet. The in-vitro drug release profile was found to be significant as compared to plain ALP suspension. The results of in-vivo studies indicate that nanosizing and enhanced solubilization of oral ALP-SNEDDS formulations significantly improved the behavioral activities compared to plain ALP suspension.

Development of poly-L-lysine multi-functionalized muco-penetrating self- emulsifying drug delivery system (SEDDS) for improved solubilization and targeted delivery of ciprofloxacin against intracellular Salmonella typhi

Salmonella typhi infections are difficult to treat due to poor penetration of current antibiotic ciprofloxacin (CIP) modalities into the intracellular compartments of macrophages owing to poor solubilization and oral bioavailability. Poor penetration and dissolution of CIP lead to development of intracellular pathogens induced multi-drug resistance and resistant biofilms formation. Here we developed a novel strategy for the design and development of mucopenetrating self-emulsifying drug delivery system (SEDDS) of CIP to target intracellular Salmonella typhi bacterium with high specificity and selectivity. Oleic oil, Tween 80, and PEG 200 were selected as oil, surfactant and co-surfactant based on solubilizing capacity and pseudo ternary diagram emulsification capability. Mucopenetration feature of the SEDDS was enhanced by inclusion of poly-L-lysine functionalized carbohydrates (mannose, preactivated hyaluronic acid) co-block pluronic F127 (PLL-M-PTHA-F127) polymeric excipient. PLL-M-PTHA-F127 was developed as an amphiphilic muco-penetrating targeted anti-bacterial biological entity for intracellular targeting of Salmonella typhi infection reservoirs. Characterization of these self-nanoemulsifying carriers was carried out via dynamic light scattering (DLS), transmission electron microscopy (TEM) and fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), x-ray diffraction (XRD) and thermogravimetric analysis (TGA) The observed hydrodynamic diameter of PLL-M-PTHA-F 127 self- nano emulsifying drug delivery system (SEDDS) was 247 nm with low PDI and negatively charged zeta potential showing the stabilization of as-prepared formulation. In vitro drug release kinetics of nanocarriers exhibited 85% sustained release within 72 h under sink conditions. PLL-M-PTHA-F127 SEDDS of CIP showed very strong killing capability against Salmonella typhi strains even at lowest concentrations as compared to CIP and were found to be hemocompatible and biocompatible. The intracellular Salmonella typhi survival rate has been minimized with PLL-M-PTHA-F127 SEDDS as compared to CIP alone. Fluorescence microscopy images confirmed the proficient cellular uptake within the intracellular compartment of macrophages and rapid gallstone biofilm dispersion/clearance activity as compared to other formulations and CIP. In summary, PLL-M-PTHA-F127-SEDDS of CIP seemed to be an ideal candidate for eradication of Salmonella typhiintracellularly.

Preparation and evaluation of a water-in-oil nanoemulsion drug delivery system loaded with salidroside

Salidroside (SAL) is a phenolic substance with high solubility and low permeability, which make it easy to cause the efflux effect of P-glycoprotein and degradation of intestinal flora, resulting in lower bioavailability. The aim of this study was to develop and optimize a water-in-oil nanoemulsion of SAL (w/o SAL-N) to explore its suitability in oral drug delivery systems. In this work, SAL-N was successfully prepared by water titration method at Km = 1 to construct the pseudo-ternary phase diagrams. Physical characterization including the average viscosity, pH, refractive index, particle size, PDI, TEM, DSC, the content of SAL, and stability study were performed. It was evaluated for drug release in vitro and pharmacokinetic studies in vivo. The optimized nanoemulsion formulation consisted of Labrafil M 1944CS (63%), Span-80/Tween-80/EtOH (27%) and 200 mg∙mL-1 SAL solution (SAL-SOL) (10%). Low viscosity and suitable pH were expected for the nanoemulsion. The spherical morphology and nanoscale size of SAL-N enhanced the stability of the nanoemulsion system. In vitro drug release showed that SAL-N had a better controlled release property than SAL-SOL at earlier time points. The pharmacokinetic studies exhibited that SAL-N had significantly higher in t1/2 (2.11-fold), AUC0-48 h (1.75-fold) and MRT0-48 h (2.63-fold) than SAL-SOL (P < 0.01). The w/o SAL-N prepared in this work can be effectively delivered via the oral route. It can be seen w/o nanoemulsion is a strategy for the drug with polyphenols to delay the release, enhance oral absorption and reduce metabolic rate.