Nanoemulsifying Drug Delivery System Research Articles

Self Nano Emulsifying Drug Delivery Systems for Oral Delivery of Hydrophobic Drugs

Self-emulsifying drug delivery systems (SNEDDS) are highly in quest due to their innumerable benefits like better portability, improved stability and higher drug loading, coupled with ease and economy of their production. SNEDDS are used to improve the solubility of high lipophilic drugs. SNEDDS are improving the oral bioavailability of limited water-soluble drug compounds. These SNEDDS are isotrophic mixtures of oil, surfactant, co-surfactant and drug that form oil in water emulsion in aqueous environment under gentle agitation. This paper presents an overview of the design, preparation and characterization, effects on the bioavailability of various drugs and various literature reports on diverse types of self-emulsifying formulations.

Development and evaluation of a solid self-nanoemulsifying drug delivery system for loratadin by extrusion-spheronization.

Recently the liquid nanoemulsifying drug delivery systems (SNEDDS) have shown dramatic effects on improving oral bioavailability of poorly soluble drugs. The main purpose of this study was to prepare a solid form of self-nanoemulsifying drug delivery system of loratadin by extrusion-spheronization. The liquid SNEDDS are generally prepared in a soft or hard gelatin capsules which suffers from several disadvantages. Therefore incorporation of SNEDDS into solid dosage form is desirable to get together the advantages of SNEDDS and solid multiparticualte systems. The SNEDDS was consisted of liquid paraffin, capriole, span 20, transcutol and loratadin as a poorly soluble drug. A multilevel factorial design was used to formulation of SNEDDS pellets, liquid SNEDDS (20 and 30%) was mixed with lactose, microcrystallin cellulose (40%) and silicon dioxide (0, 5 and 10%), and Na- crosscarmelose (0, 5 and 10%). The resulting wet mass transformed into pellets by extrusion-spheronization. The pellets were dried and characterized for size (sieve analysis), shape (image analysis), mechanical strength (friability test), droplet size (laser light scattering) and drug release rate (dissolution test). Selected SNEDDS pellets were also compared with conventional loratadin pellet or tablet formulation. The resulting SNE pellets exhibited uniform size and shape. Total friability of pellets did not affected by formulation variables. The in vitro release of SNE pellets was higher than the liquid SNE and powder tablets. Our studies demonstrated that extrusion-spheronization is a viable technology to produce self-emulsifying pellets in large scale which can improve in vitro dissolution with better solubility.

Lipid-based systems as a promising approach for enhancing the bioavailability of poorly water-soluble drugs

Low oral bioavailability as a consequence of low water solubility of drugs is a growing challenge to the development of new pharmaceutical products. One of the most popular approaches of oral bioavailability and solubility enhancement is the utilization of lipid-based drug delivery systems. Their use in product development is growing due to the versatility of pharmaceutical lipid excipients and drug formulations, and their compatibility with liquid, semi-solid, and solid dosage forms. Lipid formulations, such as self-emulsifying (SEDDS), self-microemulsifying SMEDDS) and self- -nanoemulsifying drug delivery systems (SNEDDS) were explored in many studies as an efficient approach for improving the bioavailability and dissolution rate of poorly water-soluble drugs. One of the greatest advantages of incorporating poorly soluble drugs into such formulations is their spontaneous emulsification and formation of an emulsion, microemulsion or nanoemulsion in aqueous media. This review article focuses on the following topics. First, it presents a classification overview of lipid-based drug delivery systems and mechanisms involved in improving the solubility and bioavailability of poorly water-soluble drugs. Second, the article reviews components of lipid-based drug delivery systems for oral use with their characteristics. Third, it brings a detailed description of SEDDS, SMEDDS and SNEDDS, which are very often misused in literature, with special emphasis on the comparison between microemulsions and nanoemulsions.

Cinnarizine food-effects in beagle dogs can be avoided by administration in a Self Nano Emulsifying Drug Delivery System (SNEDDS)

PurposeTo elucidate if a SNEDDS approach can eliminate the food-effect on cinnarizine absorption and to, investigate if a nutritional drink, Fresubin energy, could mimic food effect in dogs for the poorly soluble compound cinnarizine. MethodA conventional tablet, a SNEDDS capsule or a SNEDDS tablet, containing cinnarizine, were dosed to beagles dogs in fed or fasted state (n=5), with a one week wash-out period between dosing. Dogs were pre-treated with pentagastrin. Fed state was induced by a nutritional drink (Fresubin Energy®). The food-effect was evaluated by comparing Tmax, Cmax and Bioavailability (F) for the different formulations. ResultsFood effect was observed on all three parameters for the conventional tablet; Tmax was delayed 2.5times and bioavailability increased in fed state (from 20.9±5.7 to 53.8±30.1). Apart from an extended Tmax (2.5 and 3.3 times longer in fed state compared to fasted state for the SNEDDS tablets and SNEDDS capsules respectively), food effect on absorption for the SNEDDS capsules and SNEDDS tablets was not observed. The SNEDDS capsules had a higher bioavailability in both fed and fasted state compared to SNEDDS tablets (Ffasted=58.1±16.7, vs. 32.7±11.5), (Ffed=79.3±14.7 vs. 43.7±6.7) There were no significant differences in bioavailability between the conventional tablet in fed state and the SNEDDS capsules. ConclusionFood effect was observed when dosing cinnarizine with ingestion of the nutritional drink Fresubin Energy. Food effect on cinnarizine could be significantly reduced by dosing either as a SNEEDS capsule or a SNEDDS tablet, however, the SNEDDS tablet resulted in an overall lower absorption than the SNEDDS capsules in both fed and fasted state. The delay in fed state absorption could not be changed by dosing with SNEDDS formulations.

Ultra-fine self nanoemulsifying drug delivery system for transdermal delivery of meloxicam: Dependency on the type of surfactants

The aim of this study was to develop and evaluate ultra-fine selfnanoemulsifying drug delivery system (UF-SNEDDS) of meloxicam (MLX) to enhance its transdermal delivery. The preliminary screening was carried out to select SNEDDS components according to type IV lipid based formulations using surfactant and co-surfactant. The prepared SNEDDS formulations were subjected to different thermodynamic stability tests. The droplet size, polydispersity index (PDI), zeta potential, turbidity, transmission electron microscopy (TEM) and in vitro MLX release studies were investigated. Finally, the influence of UF-SNEDDS on the MLX transdermal delivery was assessed. These UF-SNEDDS showed droplet size range of 14.41±2.50nm to 25.58±2.33nm, PDI less than 0.3, zeta potential with negative charge and turbidity range of 1.92–3.47 NTU. TEM of reconstituted SNEDDS-F5 demonstrated dark smaller droplet with spherical shape. The in vitro MLX release from SNEDDS was found to be higher in comparison to saturated solution (control). An in vitro permeation study was achieved in rat skin, the permeated amount of MLX was increased up to 11.89-fold as compared to control. Then, the presence of surfactant and its type can influence on both the drug release and the transdermal delivery of MLX. These results indicated that UF-SNEDDS developed for transdermal delivery may be a promising delivery system for MLX, with high solubility and improved skin permeation.

Self nanoemulsifying drug delivery system (SNEDDS) of Rosuvastatin calcium: Design, formulation, bioavailability and pharmacokinetic evaluation

The aim of the present study is to improve solubility and bioavailability of Rosuvastatin calcium using self nanoemulsifying drug delivery system (SNEDDS). Self emulsifying property of various oils including essential oils was evaluated with suitable surfactants and co-surfactants. Ternary phase diagrams were constructed based on Rosuvastatin calcium solubility analysis for optimizing the system. The prepared formulations were evaluated for self emulsifying time, robustness to dilution, droplet size determination and zeta potential analysis. The system was found to be robust in different pH media and dilution volume. The globule size of the optimized system was less than 200nm which could be an acceptable nanoemulsion size range. The zeta potential of the selected CN 7 SNEDDS formulation (cinnamon oil 30%; labrasol 60%; Capmul MCM C8 10%) was −29.5±0.63 with an average particle size distribution of 122nm. In vitro drug release studies showed remarkable increase in dissolution of CN7 SNEDDS compared to marketed formulation. In house developed HPLC method for determination of Rosuvastatin calcium in rat plasma was used in the bioavailability and pharmacokinetic evaluation. The relative bioavailability of self nanoemulsified formulation showed an enhanced bioavailability of 2.45 times greater than that of drug in suspension. The obtained plasma drug concentration data was processed with PKSolver 2.0 and it was best fit into the one compartment model.

Formulation, Optimization and Characterization of Self Nanoemulsifying Drug Delivery System (SNEDDS) of Paclitaxel for Solubility Enhancement

Formulation, Optimization and Characterization of Self Nanoemulsifying Drug Delivery System (SNEDDS) of Paclitaxel for Solubility Enhancement

Formulation by design of felodipine loaded liquid and solid self nanoemulsifying drug delivery systems using Box–Behnken design

Objective: To design and develop liquid and solid self-nanoemulsifying drug delivery systems (SNEDDS and S-SNEDDS) of felodipine (FLD) using Box–Behnken design (BBD).Methods: Solubility study was carried out in various vehicles. Ternary phase diagram was constructed to delineate the boundaries of the nanoemulsion domain. The content of formulation variables, X1 (Acconon E), X2 (Cremophor EL) and X3 (Lutrol E300) were optimized by assessment of 15 formulations (as per BBD) for mean globule sizes in Millipore water (Y1), 0.1 N HCl (Y2), phosphate buffer (pH 6.4) (Y3); emulsification time (Y4) and T85% (Y5). The responses (Y1–Y5) were evaluated statistically by analysis of variance and response surface plots to obtain optimum points. The optimized formulations were solidified by adsorption to solid carrier technique using Aerosil 200 (AER).Results and discussion: Transmission electron microscopy images confirmed the spherical shape of globules with the size range concordant with the globule size analysis by dynamic light scattering technique (<60 nm). The surface morphology of S-SNEDDS (before release) by scanning electron microscopy and atomic force microscopy indicated that SNEDDS are adsorbed uniformly on the surface of AER. The dried residue of S-SNEDDS (after release) revealed the presence of nanometric pores vacated by the previously adsorbed SNEDDS onto AER. Differential scanning calorimetry and X-ray powder diffraction studies illustrated the change of FLD from crystalline to amorphous state.Conclusion: This study indicates that owing to nanosize, SNEDDS and S-SNEDDS of FLD have potential to enhance its absorption and may serve an efficient oral delivery.

Improved Oral Bioavailability of BCS Class 2 Compounds by Self Nano-Emulsifying Drug Delivery Systems (SNEDDS): The Underlying Mechanisms for Amiodarone and Talinolol

Superior bioavailability of BCS Class 2 compounds incorporated into SNEDDS was previously reported. This study aims to elucidate the underlying mechanisms accountable for this phenomenon. SNEDDS of amiodarone (AM) and talinolol were developed. Pharmacokinetic parameters were assessed in vivo. Effect on intestinal permeability, P-gp efflux and toxicity was evaluated in vitro (Caco-2) and ex vivo (Ussing). Solubilization was assessed in vitro (Dynamic Lipolysis Model). Effect on intraenterocyte metabolism was evaluated using CYP3A4 microsomes. Oral administration of AM-SNEDDS and talinolol-SNEDDS resulted in higher and less variable AUC and Cmax. In vitro, higher talinolol-SNEDDS Papp indicated Pgp inhibition. Lipolysis of AM-SNEDDS resulted in higher AM concentration in the fraction available for absorption. Incubation of AM-SNEDDS with CYP3A4 indicated CYP inhibition. SNEDDS didn't alter mannitol Papp and TEER. SNEDDS effect was transient. Multiple mechanisms are accountable for improved bioavailability and reduced variability of Class-2 compounds by SNEDDS: increased solubilization, reduced intraenterocyte metabolism and reduced P-gp efflux. SNEDDS effect is reversible and doesn't cause intestinal tissue or cell damage. These comprehensive findings can be used for intelligent selection of drugs for which oral bioavailability will improve upon incorporation into SNEDDS, based on recognition of the drug's absorption barriers and the ability of SNEDDS to overcome them.

Validated spectrofluorometric method for determination of gemfibrozil in self nanoemulsifying drug delivery systems (SNEDDS)

A spectrofluorometric method has been developed and validated for the determination of gemfibrozil. The method is based on the excitation and emission capacities of gemfibrozil with excitation and emission wavelengths of 276 and 304nm respectively. This method allows de determination of the drug in a self-nanoemulsifying drug delivery system (SNEDDS) for improve its intestinal absorption. Results obtained showed linear relationships with good correlation coefficients (r2>0.999) and low limits of detection and quantification (LOD of 0.075μgmL−1 and LOQ of 0.226μgmL−1) in the range of 0.2–5μgmL−1, equally this method showed a good robustness and stability. Thus the amounts of gemfibrozil released from SNEDDS contained in gastro resistant hard gelatine capsules were analysed, and release studies could be performed satisfactorily.

Improved Oral Delivery of Rosuvastatin by Using Self Nanoemulsifying Drug Delivery System

The aim of the present study was to develop a self nanoemulsifying drug delivery system (SNEDDS) for the improved oral delivery of Rosuvastatin, a lipid lowering agent. Captex 810D, based on the higher solubility of Rosuvastatin was selected as an oil phase. Mixture of permeation enhancers such as Solutol HS15 and Acconon MC8 was selected as surfactants for the formulation of SNEDDS. Formulated SNEDDS upon mixing with water, dispersed rapidly into fine droplets size ranging from 95-263nm. Further the SNEDDS was evaluated for self nanoemulsification time, precipitation, cloud point, morphology, in-vitro drug release and ex-vivo permeation. Formulation (F3) showed the globule size of 139nm, quick self nanoemulsifiation time (20 sec) and transparency (97%). Maximum drug release of 99.9% and higher drug permeation of 95% was observed with formulation F3 when compared with conventional tablet. The formulated SNEDDS can be used to improve the oral absorption and bioavailability of Rosuvastatin.

SNEDDS curcumin formulation leads to enhanced protection from pain and functional deficits associated with diabetic neuropathy: An insight into its mechanism for neuroprotection

Curcumin has shown to be effective against various diabetes related complications. However major limitation with curcumin is its low bioavailability. In this study we formulated and characterized self nano emulsifying drug delivery system (SNEDDS) curcumin formulation to enhance its bioavailability and then evaluated its efficacy in experimental diabetic neuropathy. Bioavailability studies were performed in male Sprague Dawley rats. Further to evaluate the efficacy of formulation in diabetic neuropathy various parameters like nerve function and sensorimotor perception were assessed along with study of inflammatory proteins (NF-κB, IKK-β, COX-2, iNOS, TNF-α and IL-6). Nanotechnology based formulation resulted in prolonged plasma exposure and bioavailability. SNEDDS curcumin provided better results against functional, behavioural and biochemical deficits in experimental diabetic neuropathy, when compared with naive curcumin. Further western blot analysis confirmed the greater neuroprotective action of SNEDDS curcumin. SNEDDS curcumin formulation due to higher bioavailability was found to afford enhanced protection in diabetic neuropathy. From the Clinical EditorIn this study the authors formulated and characterized a self-emulsifying drug delivery system for formulation to enhance curcumin bioavailability in experimental diabetic neuropathy. Enhanced efficacy was demonstrated in a rat model.

Self Nanoemulsifying Drug Delivery System of Olanzapine for Enhanced Oral Bioavailability: In vitro, In vivo Characterisation and In vitro -In vivo Correlation

Lipid based self nanoemulsifying drug delivery system (SNEDDS) was explored to improve the oral bioavailability of olanzapine (OLZ), a poorly water-soluble drug candidate, using spontaneous emulsification method. Nanoemulsions have ability to enhance the oral bioavailability of poorly water soluble or lipophilic drugs through selective lymphatic pathways. Following optimization, (from pseudo ternary phase diagram) OLZ SNEDDS consisting of Capryol 90(36.2%), Brij 97(14.6%) and ethanol (42.5%) were selected. The globule size (90 nm), and polydispersity index (0.287), was found to be minimum. The pharmacokinetic study was conducted on rabbits and the parameters like peak concentration (Cmax), time of peak concentration (Tmax), etc. were evaluated by Wagner nelson method. The in vivo studies concluded that there was 1.2 fold and 1.6 fold increase in bioavailability of nanoemulsion when compared with marketed tablet formulation and drug suspension, respectively. This may be attributed to increased solubility and enhanced permeability of the drug from nanosized emulsion. From the similarity factor between biorelevent dissolution media and 0.1 N HCl (pH 1.6) it was concluded that the 0.1 N HCl (pH 1.6) can be used for the dissolution of SNEDDS to predict the in vivo bioavailability instead of the biorelavent media. The level A correlation with correlation factor 0.97 was achieved, which showed that there is a good correlation between in vitro dissolution and in vivo bioavailability and the dissolution studies can be used as a surrogate for the in vivo studies.

Optimization of self nanoemulsifying drug delivery system for poorly water-soluble drug using response surface methodology

There is an increasing interest on self-nanoemulsifying drug delivery system (SNEDDS) for oral delivery of poorly water-soluble drugs. However, development of SNEDDS is often driven by empiric, pseudo-ternary diagrams and solubility of drugs, and it is lacking a systematic approach for evaluating impact of excipients on the performance of formulations as well as the fate of drug. The aim of this study was to rationalize the SNEDDS development procedure and to get a better understanding on the role of excipients on the SNEDDS. The formulations consist of soybean oil or rapeseed oil, Cremophor® RH40, Maisine™ 35-1 and ethanol. Response surface methodology (RSM) was used in the development of SNEDDS. Significant advantages of RSM were found in reducing the work load and determining the impact of excipients on formulation characteristics. The most significant factor in influencing droplet size was the co-surfactant Maisine™ 35-1, the droplet size increased with increasing concentration of Maisine™ 35-1. It suggests that Maisine™ 35-1 has double functions in the SNEDDS; it functions as co-surfactant to improve the emulsification of oil, meanwhile it also works as the oil phase and results in larger droplets. A significant reduction in droplet size was interestingly observed when fenofibrate was loaded in the vehicles, probably due to the surface activity of fenofibrate, promoting the self-emulsifying process. It was evident that drug precipitation during lipolysis was not affected by the level of co-solvent ethanol in the formulation, while it had pronounced impact on drug solubilization during the initial dispersion stage.

An Excellent Delivery System for Improving the Oral Bioavailability of Natural Vitamin E in Rats

This study set out to develop a novel and stable nanoemulsion formulation of natural vitamin E with increased oral bioavailability. The natural vitamin E nanoemulsion was prepared by a modified emulsification technique. The physicochemical characteristics of natural vitamin E nanoemulsion were characterized and its pharmacokinetics study was performed as well. The experimental results showed droplet diameters ranging from 20 to 400 nm (average, 87.7 nm) with a negative electrostatic potential (-23.5 ± 1.5 mv). The pharmacokinetics study of this nanoemulsion and corresponding soft capsule was carried out using noncompartment model method. Compared with the marketed soft capsule, the C (max) of the natural vitamin E nanoemulsion was higher, while the T (max) was shorter. Thus, plasma concentration-time profiles in rats dosed with nanoemulsion showed a 1.6-fold enhancement in the area under the curve of natural vitamin E compared with the marketed soft capsule. The antioxidative effects of the natural vitamin E nanoemulsion and the marketed soft capsule were also evaluated by the levels of superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentration in serum and liver tissue. According to the SOD activity and the MDA concentration determined, the nanoemulsion was superior to the marketed soft as an antioxidative agent. The overall results demonstrated that the nanoemulsion drug delivery system could be a promising strategy for the delivery of natural vitamin E, which showed great potential for clinical application.

Contribution of Formulation and Excipients Towards Enhanced Permeation of Curcumin

Curcumin (CRM) (CAS number 458-37-07), a naturally-occurring molecule, has diverse pharmacological actions. Recently our research group demonstrated that poor permeability also contributes to its poor oral bioavailability. A self nano-emulsifying drug delivery system (CRM SNEDDS) consisting of Labrasol, Gelucire 44/14, Vitamin E TPGS and PEG 400 was designed and provided 16 times improvement in oral bioavailability in rats, at a dose of 250 mg/kg body weight. Caco-2 cell transport studies were conducted for CRM SNEDDS and CRM in the presence of individual excipients, to determine the extent of improvement in permeability. Papp values for CRM, CRM SNEDDS and CRM in combination with 4 individual excipients were calculated. Transepithelial electrical resistance value was assessed to evaluate the cell morphology and the cellular tight junctions. Permeation of a transcellular marker, Lucifer Yellow was used as a marker to assess monolayer integrity. The tested excipient concentrations were found to be non-toxic to the cell monolayer in 2 h incubation. Results showed that the Papp increased 6.35 times for curcumin in CRM SNEDDS as compared to CRM. Individual excipients enhanced permeation from 1.97 to 6.35 times, with Labrasol showing the highest enhancement of 6.35 times.

Development and characterization of a novel nanoemulsion drug-delivery system for potential application in oral delivery of protein drugs

Background:The stability of protein drugs remains one of the key hurdles to their success in the market. The aim of the present study was to design a novel nanoemulsion drug-delivery system (NEDDS) that would encapsulate a standard-model protein drug – bovine serum albumin (BSA) – to improve drug stability.Methods:The BSA NEDDS was prepared using a phase-inversion method and pseudoternary phase diagrams. The following characteristics were studied: morphology, size, zeta potential, drug loading, and encapsulation efficiency. We also investigated the stability of the BSA NEDDS, bioactivity of BSA encapsulated within the NEDDS, the integrity of the primary, secondary, and tertiary structures, and specificity.Results:The BSA NEDDS consisted of Cremophor EL-35, propylene glycol, isopropyl myristate, and normal saline. The average particle diameter of the BSA NEDDS was about 21.8 nm, and the system showed a high encapsulation efficiency (>90%) and an adequate drug-loading capacity (45 mg/mL). The thermodynamic stability of the system was investigated at different temperatures and pH levels and in room-temperature conditions for 180 days. BSA NEDDS showed good structural integrity and specificity for the primary, secondary, and tertiary structures, and good bioactivity of the loaded BSA.Conclusions:BSA NEDDS showed the properties of a good nanoemulsion-delivery system. NEDDS can greatly enhance the stability of the protein drug BSA while maintaining high levels of drug bioactivity, good specificity, and integrity of the primary, secondary, and tertiary protein structures. These findings indicate that the nanoemulsion is a potential formulation for oral administration of protein drugs.

Oil based nanocarrier system for transdermal delivery of ropinirole: A mechanistic, pharmacokinetic and biochemical investigation

Ropinirole, a recent introduction in the clinical treatment of Parkinson's disease, suffers with the problems of low oral bioavailability and frequent dosing. An effective transdermal nano-emulsion drug delivery system can however resolve these issues effectively with greater therapeutic benefits and clinical significance. Therefore, the present work focuses precisely on pharmacokinetic, biochemical and mechanistic assessment of transdermal nanoemulsion gel in rats induced with Parkinson lesioned brain by 6-OHDA. DSC and FT-IR studies showed that NEG affects the normal lipid packing of stratum corneum to enhance the drug permeation. Study of pharmacokinetic parameters (AUC, C max, and T max) revealed a greater and more extended release of ropinirole from nanoemulsion gel compared to that from a conventional gel (RPG) and oral marketed tablet (Ropitor ®). The AUC 0→∞ for RPCNG and RPTNG was found to be 928.07 ± 206.5 and 1055.99 ± 251.7 ng h/mL, respectively in comparison to 137.25 ± 31.3 and 467.15 ± 106.1 ng h/mL for RPG and oral tablet, respectively. The relative bioavailability of ropinirole has been enhanced more than two fold by RPTNG. Furthermore, antiparkinson activity was evaluated in terms of estimating the level of thiobarbituric acid reactive substances, glutathione antioxidant enzymes and catalase in lesioned brain of rats. Formulations were also found to be non-toxic and non-irritant by histological investigations.

Preparation and In Vivo Evaluation of Self-Nanoemulsifying Drug Delivery System (SNEDDS) Containing Ezetimibe

Ezetimibe is a poorly water-soluble drug with varying bioavailability. The main objective of present work was to develop self nanoemulsifying drug delivery system (SNEDDS) for enhancing solubility and bioavailability of ezetimibe, which is widely used in treatment of homozygous familial hypercholesterolemia and homozygous sitosterolemia. The formulation of ezetimibe SNEDDS was optimized by simplex lattice design, multiple regression analysis and ternary contour plot. The optimal formulation of SNEDDS comprised of 7.058% oil (Oleic acid), 82.94% surfactant (Tween-80) and 10.0% co-surfactant (PEG-400). Pseudo-ternary phase diagrams were constructed to identify the efficient self-emulsification region. The average globule size of SNEDDS containing ezetimibe was about 90.63 nm when diluted with water. No significant variations in globule size and ezetimibe content in SNEDDS were observed over a period of 3 months at 40 ± 2° C/75 ± 5% RH and 25 ± 3° C (room temperature). In vitro diffusion studies showed remarkable increase in diffusion of drug. In vivo studies (in rats) showed significant increase in absorption of drug as compared to plain drug and marketed formulation. The data suggested use of SNEDDS to provide great potential as alternative to traditional oral formulations of ezetimibe. Keywords: Ezetimibe, Self nanoemulsifying drug delivery system (SNEDDS), Simplex lattice design, globule size, Hyperlipidemia, Oleic acid, Tween-80, Polyethylene glycol-400, Zeta potential, In vivo pharmacokinetic

Study of cosurfactant effect on nanoemulsifying area and development of lercanidipine loaded (SNEDDS) self nanoemulsifying drug delivery system

The present study deals with the development and characterization of self-nanoemulsifying drug delivery system (SNEDDS) to improve the oral bioavailability of poorly soluble third generation calcium channel blocker lercanidipine (LER). Solubility of the LER was estimated in various oils, cosurfactants and surfactants which were grouped into two different combinations to construct pseudoternary phase diagrams. Various thermodynamic stability and dispersibility tests were performed on the formulations from phase diagram. After constructing phase diagram of two different combinations NL-I and NL-II, the effect of cosurfactants on the nanoemulsifying area was studied and the effect of number and length of hydrophobic alkyl chains of cosurfactant in its emulsification capacity was proved. Percentage transmittance, emulsification time, viscosity and droplet size analysis were used to characterize optimized formulations. The optimized formulation composed of Cremophor EL (45% wt/wt), (13.5% wt/wt) Caproyl 90 with (1.5% wt/wt) Transcutol® HP as per limits of inactive ingredients guidelines of FDA and Maisine oil (10% wt/wt). The mean droplet size in selected nanocarrier system was 20.01 nm. The in vitro dissolution profile of LER SNEDDS was found significant in comparison to the marketed LER (Zanidip) tablet and pure drug in pH 1.2, 4.5 and 6.8 buffers. Empty hard gelatin capsule shells were filled using Pfizer's Licap technology and charged on stability conditions of 30 °C/65% RH, 40 °C/65%RH and 50 °C/75% in glass bottles where no significant degradation (p>0.05) was observed in 3 months. The results indicate that SNEDDS of LER, owing to nanosized, has potential to enhance the absorption of drug.