Nanocarrier-based topical drug delivery for an antifungal drug

Objective: The conventional liposomal amphotericin B causes many unwanted side effects like blood disorder, nephrotoxicity, dose-dependent side effects, highly variable oral absorption and formulation-related instability. The objective of the present investigation was to develop cost-effective nanoemulsion as nanocarreir for enhanced and sustained delivery of amphotericin B into the skin.

Methods and characterizations: Different oil-in-water nanoemulsions were developed by varying the composition of hydrophilic (Tween® 80) surfactants and co-surfactant by the spontaneous titration method. The developed formulation were characterized, optimized, evaluated and compared for the skin permeation with commercial formulation (fungisome 0.01% w/w). Optimized formulations loaded with amphotericin B were screened using varied concentrations of surfactants and co-surfactants as decided by the ternary phase diagram.

Results and discussion: The maximum % transmittance obtained were 96.9?±?1.0%, 95.9?±?3.0% and 93.7?±?1.2% for the optimized formulations F-I, F-III and F-VI, respectively. These optimized nanoemulsions were subjected to thermodynamic stability study to get the most stable nanoemulsions (F-I). The results of the particle size and zeta potential value were found to be 67.32?±?0.8 nm and –3.7?±?1.2?mV for the final optimized nanoemulsion F-I supporting transparency and stable nanoemulsion for better skin permeation. The steady state transdermal flux for the formulations was observed between 5.89?±?2.06 and 18.02?±?4.3?µg/cm²/h whereas the maximum enhancement ratio were found 1.85- and 3.0-fold higher than fungisome and drug solution, respectively, for F-I. The results of the skin deposition study suggests that 231.37?±?3.6?µg/cm² drug deposited from optimized nanoemulsion F-I and 2.11-fold higher enhancement ratio as compared to fungisome. Optimized surfactants and co-surfactant combination-mediated transport of the drug through the skin was also tried and the results were shown to have facilitated drug permeation and skin perturbation (SEM).

Conclusion: The combined results suggested that amphotericin B nanoemulsion could be a better option for localized topical drug delivery and have greater potential as an effective, efficient and safe approach.     

Solid lipid nanoparticles as vesicles for oral delivery of olmesartan medoxomil: formulation,optimization and in vivo evaluation

Objective: Olmesartan medoxomil (OLM) is an antihypertensive drug with low oral bioavailability (28%) resulting from poor aqueous solubility, presystemic metabolism and P-glycoprotein mediated efflux. The present investigation studies the role of lipid nanocarriers in enhancing the OLM bioavailability through oral delivery.

Materials and methods: Solid lipid nanoparticles (SLN) were prepared by solvent emulsion-evaporation method. Statistical tools like regression analysis and Pareto charts were used to detect the important factors effecting the formulations. Formulation and process parameters were then optimized using mean effect plot and contour plots. The formulations were characterized for particle size, size distribution, surface charge, percentage of drug entrapped in nanoparticles, drug–excipients interactions, powder X-ray diffraction analysis and drug release in vitro.

Results and discussion: The optimized formulation comprised glyceryl monostearate, soya phosphatidylcholine and Tween 80 as lipid, co-emulsifier and surfactant, respectively, with an average particle size of 100?nm, PDI 0.291, zeta potential of ?23.4?mV and 78% entrapment efficiency. Pharmacokinetic evaluation in male Sprague Dawley rats revealed 2.32-fold enhancement in relative bioavailability of drug from SLN when compared to that of OLM plain drug on oral administration.

Conclusion: In conclusion, SLN show promising approaches as a vehicle for oral delivery of drugs like OLM.     

Formulation of garlic oil‐in‐water nanoemulsion: antimicrobial and physicochemical aspects

Despite the unique properties, application of garlic essential oil (GEO) is too limited in food and drugs, due to its low water solubility, very high volatility and unpleasant odour. In this work, a nanoemulsion containing GEO was formulated to cover and protect the volatile compounds of GEO. The encapsulation efficiency of formulated nanoemulsions was measured by gas chromatography and obtained encapsulation efficiency ranged from 91 to 77% for nanoemulsions containing 5–25% GEO, respectively. The 2,2‐diphenyl‐1‐picrylhydrazyl method for antioxidant activity measurement showed that free radical scavenging capacity of nanoemulsions intensified during storage time. The electrical conductivity of the samples was constant over storage time while linearly increased by raising the temperature. Thermogravimetric analysis was used to determine the thermal resistance of nanoemulsions and their ingredients. Interestingly, microbial tests cleared that the control nanoemulsion with a particle size below 100 nm (nanoemulsion without GEO) also showed antimicrobial activity. Disk diffusion method showed that pure GEO and also formulated nanoemulsions had a stronger effect against Gram‐positive bacterium (Staphylococcus aureus) than Gram‐negative bacterium (Escherichia coli).Inspec keywords: emulsions, nanostructured materials, antibacterial activity, microorganisms, electrical conductivity, thermal analysis, thermal resistance, oils, nanobiotechnology, food safety, cellular biophysicsOther keywords: garlic oil‐in‐water nanoemulsion, antimicrobial aspects, physicochemical aspects, garlic essential oil, GEO, volatile compounds, encapsulation efficiency, gas chromatography, 2,2‐diphenyl‐1‐picrylhydrazyl method, antioxidant activity measurement, free radical scavenging capacity, storage time, electrical conductivity, thermogravimetric analysis, thermal resistance, antimicrobial activity, disk diffusion method, Gram‐positive bacterium, Staphylococcus aureus, Gram‐negative bacterium, Escherichia coli     

Use of sorbitol as pharmaceutical excipient in the present day formulations – issues and challenges for drug absorption and bioavailability

Sorbitol is a popular sugar alcohol which has been used as an excipient in formulations of various drugs. Although from a safety perspective the presence of sorbitol in drug formulations does not raise a concern, reports have emerged and these suggest that sorbitol in drug formulations may alter oral absorption and bioavailability of certain drugs. The focus of this article was to review the published literature of various drugs where pharmacokinetic data has been reported for the drug alone versus drug administered with sorbitol and provide perspectives on the pharmacokinetic findings. Interestingly, for BCS class I drugs such as theophylline, metoprolol, the oral absorption, and bioavailability were generally not affected by sorbitol. However, theophylline oral absorption and bioavailability were decreased when sustained release formulation was used in place of immediate release formulation. For drugs such as risperidone (BCS class II) and lamivudine and ranitidine (BCS class III), the solution formulations showed diminished oral bioavailability in presence of sorbitol, whereas cimetidine and acyclovir (BCS class III), did not show any changes in pharmacokinetic profiles due to sorbitol. Finally, the presence of activated charcoal with sorbitol showed different pharmacokinetic outcome for BCS class I and II drugs.     

Enhancement of the oral bioavailability of breviscapine by nanoemulsions drug delivery system

Aim to design an effective breviscapine nanoscale drug delivery system to realize the improvement of its oral bioavailability. Based on the investigations of the stabilities in the gastrointestinal tract (GIT), permeation and efflux across the cell membrane, the breviscapine nanoemulsion (NE) was formulated and evaluated in vitro and in vivo. The globule size and polydispersity index of the NE was 45.6?nm and 0.105, and the efficient encapsulation was 95.2%. In vitro, the drug release from NEs in pH 6.8 PBS fit to the first-order kinetics. The Caco-2 cell transport experiments showed that the breviscapine NE facilitated the improvement of the apparent permeability coefficient (P_app) from the apical side to basilar side compared with the free drug. In vivo, the relative bioavailability of breviscapine NE reached to 249.7%. All the studies implicated that the NE carrier contributed to the enhancement of the oral absorption of breviscapine due to the improved stability and permeation in the GIT. The nanoemulsions technology is better for the poor permeable and unstable active agents in GIT as well as helps the industrial scale process.     

Enhanced oral bioavailability of tacrolimus in rats by self-microemulsifying drug delivery systems

A new self-microemulsifying drug delivery system (SMEDDS) has been developed to increase the solubility, dissolution rate and oral bioavailability of tacrolimus (TAC). The formulations of TAC-SMEDDS were optimized by solubility assay, compatibility tests, and pseudo-ternary phase diagrams analysis. In order to inhibit the efflux of P-glycoprotein (P-gp) for tacrolimus, which is the substrate of P-gp, the excipients which show the inhibition effect to P-gp, such as tocopheryl polyethylene glycol succinate (TPGS) and Cremophor EL40, were chosen in the SMEDDS formulations. According to particle size and the rate of self-emulsification, two optimized formulations were selected: Miglyol 840 as oil phase, Transcutol P as cosurfactant, TPGS as surfactant (TPGS-SMEDDS) or Cremophor EL40 as surfactant (Crem-SMEDDS), respectively. The ratio of oil phase, surfactant and cosurfactant is 1:7.2:1.8. The mean droplet size distribution of the optimized SMEDDS was less than 20?nm. The in vitro dissolution test indicated a significant improvement in release characteristics of TAC. The prepared SMEDDS was compared with the homemade solution by administering the hard capsule to fasted rats. The absorption of TAC from TPGS-SMEDDS and Crem-SMEDDS form resulted in about sevenfold and eightfold increase in bioavailability compared with the homemade solution. Our study illustrated the potential use of SMEDDS for the delivery of hydrophobic compounds, such as TAC by the oral route.     

Antibacterial activity of cationised and non-cationised placebo lipidic nanoemulsion using transmission electron microscopy

The primary aim of the study was to observe the morphological changes taking place on Escherichia coli when treated with non-cationised placebo lipidic emulsion (NCPLE) and cationised placebo lipidic emulsion (CPLE). The particle size of NCPLE and CPLE indicated the mean diameter of 10.77 ± 0.20 nm and 56.98 ± 1.718 nm, respectively. The zeta potential of NCPLE and CPLE depicted the potential of ?10.8 ± 0.80 mV and +20.9 ± 3.25 mV, respectively. Agar diffusion study indicated higher inhibition zone of 21.4 ± 0.85 mm for CPLE as evaluated against 14.7 ± 0.76 mm for NCPLE. Transmission electron micrographs of Escherichia coli treated with NCPLE and CPLE showed the potential of blank nanoemulsions as antibacterial, which can be used as a therapeutic agent. The bacterial cell being negatively charged attracts the cationised nanoemulsions from the bulk of dispersion. As the concentration of nanoemulsion increased in the vicinity of the bacterial cell, the degree of collisions increased between the cationised nanoemulsion leading to coalescence and the formation of a pool of emulsion containing bacterial cells leading to cell death. The study demonstrated that placebo lipidic nanoemulsion (NCPLE & CPLE) may itself be used as an active therapeutic agent for the treatment of bacterial infections. Moreover, it can also be used as a carrier system for antibacterial drugs for the two-pronged synergistic effect.     

Nanosuspension formulations for low-soluble drugs: pharmacokinetic evaluation using spironolactone as model compound

Various particle sizes of spironolactone as a model low solubility drug were formulated to yield micro-and nanosuspensions of the type solid lipid nanoparticles and DissoCubes. Seven oral and one i.v. formulations were tested in an in vivo pharmacokinetic study in rats with the aim of characterizing the bioavailability of spironolactone on the basis of its metabolites canrenone and 7-alpha-thiomethylspirolactone. In addition, a dose escalation study was carried out using nonmicronized spironolactone suspension as well as a nanosuspension type DissoCubes. On the basis of AUC as well as Cmax ratios, three groups of formulations were distinguished. The biggest improvement was seen with a solid lipid nanoparticle formulation yielding a 5.7-fold increase in AUC for canrenone and a similar improvement based on the Cmax metric, followed by a group of three formulations containing nanosized, micronized, and coarse drug material and surfactant. The DissoCubes nanosuspension yielded highly significant improvements in bioavailability averaging 3.3-fold in AUC and 3.0-fold in terms of Cmax for canrenone. The third class encompasses all other formulations, which showed very little to no improvement in bioavailability. The results show that the particle size minimization was not the major determining factor in the bioavailability improvement. Rather, the type of surfactant used as stabilizer in the formulations was of greater importance. Improvement in drug solubility in the intestine as well as in dissolution rate of spironolactone are the most likely mechanisms responsible for the observed effect, although additional mechanisms such as permeability enhancement may also be involved.     

Development and comparative anti-microbial evaluation of lipid nanoparticles and nanoemulsion of Polymyxin B

Polymyxin B is a decapeptide, mainly used for the treatment of gram-negative bacteremia. It was anticipated that a prolongation of release may lead to a more efficacious therapy. Lipid nanoparticles and nanoemulsion were formulated and comparatively evaluated for their properties. Lipid nanoparticles of Polymyxin B Sulphate with a mean particle size of 186.9 nm (Polydispersity Index 0.235) were prepared by nano-precipitation technique and nanoemulsion was prepared under the conditions of spontaneous formation with a mean globule size 125.0 nm (Polydispersity Index 0.291). The lipid nanoparticles were screened for lipid load from 0.1-1% along with 1-10% surfactant while in the optimization of nanoemulsion different ratios of oil, surfactant, and co-surfactant were evaluated. The developed systems were taken up for comparative anti-microbial study against a sensitive strain of E. coil using Turbidimetry as the method for monitoring the growth of microorganisms in a time dependent manner. Results of the study using ANOVA revealed an initial comparable activity with no statistical difference between the free drug, lipid nanoparticles, and the nanoemulsion. The anti-microbial effect was significantly sustained by lipid nanoparticles over a period of 18 hr but could not be sustained in case of nanoemulsion after 12 hr. Further, in order to assess anti-microbial activity of the developed delivery templates, a similar study was carried out using the lipid nanoparticles and nanoemulsion without the incorporation of drug. The results showed only a mild anti-microbial action for drug-free lipid nanoparticles but significant activity was exerted by drug-free nanoemulsion against plain drug throughout the study. It was concluded that the developed lipid nanoparticles and nanoemulsion are promising delivery vectors for the anti-microbial drugs. Further, lipid nanoparticles could give an initial as well as sustained effect while the nanoemulsion was capable of exerting potent effect for a shorter period of time.     

Simulation of fusion-mediated nanoemulsion interactions with model lipid bilayers

Perfluorocarbon-based nanoemulsion particles have become promising platforms for the delivery of therapeutic and diagnostic agents to specific target cells in a non-invasive manner. A "contact-facilitated" delivery mechanism has been proposed wherein the emulsifying phospholipid monolayer on the nanoemulsion surface contacts and forms a lipid complex with the outer monolayer of target cell plasma membrane, allowing cargo to diffuse to the surface of target cell. While this mechanism is supported by experimental evidence, its molecular details are unknown. The present study develops a coarse-grained model of nanoemulsion particles that are compatible with the MARTINI force field. Simulations using this coarse-grained model have demonstrated multiple fusion events between the particles and a model vesicular lipid bilayer. The fusion proceeds in the following sequence: dehydration at the interface, close apposition of the particles, protrusion of hydrophobic molecules to the particle surface, transient lipid complex formation, absorption of nanoemulsion into the liposome. The initial monolayer disruption acts as a rate-limiting step and is strongly influenced by particle size as well as by the presence of phospholipids supporting negative spontaneous curvature. The core-forming perfluorocarbons play critical roles in initiating the fusion process by facilitating protrusion of hydrophobic moieties into the interface between the two particles. This study directly supports the hypothesized nanoemulsion delivery mechanism and provides the underlying molecular details that enable engineering of nanoemulsions for a variety of medical applications.     

Development of industrially feasible concentrated 30% and 40% nanoemulsions for intravenous drug delivery

Emulsions for parenteral nutrition loaded with drugs are used for optimized drug delivery, but in case of poorly oil soluble drugs, the injection volume can be too large when using commercial 10-20% oil emulsions. To reduce the injection volume, the feasibility of producing injectable, physically stable concentrated emulsions up to 40% oil content was investigated. Emulsions were made from fish oil, stabilized with egg lecithin, using high-pressure homogenization. Emulsions with oil contents of 10%-40% were investigated to assess basic correlations between increasing oil content, applied production pressures, homogenization cycles and resulting bulk droplet size, content of larger particles, zeta potential, viscosity and short-term stability. The observed correlations showed that in high-pressure homogenization, the contribution of the dispersive effect dominated the coalescence effect at low and Optimum production conditions for 30% and 40% nanoemulsions, i.e. 800 bar and 2 -3 homogenization cycles, were established on lab scale. These production conditions are industrially feasible. The obtained droplet sizes (about 200?nm) and the content of larger droplets were comparable to 10% commercial emulsions of parenteral nutrition, being important for in vivo tolerability and organ distribution. Despite the high oil concentration, the viscosity of the nanoemulsions was sufficiently low for injection. The short-term storage study showed physical stability for 1 month. A concentrated nanoemulsion base formulation from regulatory accepted excipients is now available, ready for loading with drugs.     

Development of industrially feasible concentrated 30% and 40% nanoemulsions for intravenous drug delivery

Emulsions for parenteral nutrition loaded with drugs are used for optimized drug delivery, but in case of poorly oil soluble drugs, the injection volume can be too large when using commercial 10–20% oil emulsions. To reduce the injection volume, the feasibility of producing injectable, physically stable concentrated emulsions up to 40% oil content was investigated. Emulsions were made from fish oil, stabilized with egg lecithin, using high-pressure homogenization. Emulsions with oil contents of 10%–40% were investigated to assess basic correlations between increasing oil content, applied production pressures, homogenization cycles and resulting bulk droplet size, content of larger particles, zeta potential, viscosity and short-term stability. The observed correlations showed that in high-pressure homogenization, the contribution of the dispersive effect dominated the coalescence effect at low and Optimum production conditions for 30% and 40% nanoemulsions, i.e. 800 bar and 2 -3 homogenization cycles, were established on lab scale. These production conditions are industrially feasible. The obtained droplet sizes (about 200?nm) and the content of larger droplets were comparable to 10% commercial emulsions of parenteral nutrition, being important for in vivo tolerability and organ distribution. Despite the high oil concentration, the viscosity of the nanoemulsions was sufficiently low for injection. The short-term storage study showed physical stability for 1 month. A concentrated nanoemulsion base formulation from regulatory accepted excipients is now available, ready for loading with drugs.     

Nanomedicine-nanoemulsion formulation improves safety and efficacy of the anti-cancer drug paclitaxel according to preclinical assessment

Paclitaxel is an important anticancer drug and is currently used to treat a variety of cancers, including ovarian carcinomas, breast cancer, non-small cell lung cancer, and AIDS-related Kaposi's sarcoma. The objectives of the studies were to assess and compare the safety and efficacy of EmPAC (a newly developed nanoemulsion formulation of paclitaxel) versus Taxol (the injectable formulation of paclitaxel involving the use of polyethylated or polyoxyl castor oil currently used in the clinic). The objectives were also to investigate the mechanism for the improved safety and efficacy of EmPAC over Taxol. These results showed that EmPAC had better anti-tumor efficacy than Taxol, according to in vitro cell culture studies and studies in animal tumor models. EmPAC had improved anti-tumor efficacy even in tumor cell lines that are known to be multi-drug resistant. Part of the mechanism of action for the improved efficacy may be related to EmPAC inducing greater cellular uptake of paclitaxel into tumor cells than Taxol did, according to the in vitro cell culture radioactive-labeled studies and in vitro cell culture antibody studies. It may also partly be because EmPAC delivered more paclitaxel to the tumor mass than Taxol, while the delivery of paclitaxel to other tissues (e.g., blood, muscle, liver, spleen, kidney and lung) were similar between the two formulations of paclitaxel, according to studies in animals with tumor xenograft. EmPAC also had better safety than Taxol according to toxicology studies in rabbits. This may be because EmPAC does not contain the toxic ingredients used in formulating Taxol (such as polyethylated or polyoxyl castor oil). These results support the clinical development of the nanoemulsion formulation of paclitaxel.     

Improved Bioavailability of a Micronized Megestrol Acetate Tablet Formulation in Humans

Megestrol acetate, a progestogen widely used in the palliative treatment of endometrial carcinoma and breast cancer, is currently administered orally as a solid dosage form. Bioavailability of the drug following oral administration is closely related to the effectiveness and safety profile of the drug in formulation. Improved immediate-release formulations should allow improved drug delivery into the systemic circulation and, at the end, to the site of action. The micronization of drugs is one of the technological procedures to achieve such a purpose. This paper reports the design and results obtained in an in vivo study of the bioavailability of a micronized megestrol acetate tablet formulation compared to a conventional form. A significant increase in the drug bioavailability was observed, in either the rate or the extent of absorption. In vitro dissolution data of the two study formulations reflected the in vivo findings.     

Improved bioavailability of a micronized megestrol acetate tablet formulation in humans

Megestrol acetate, a progestogen widely used in the palliative treatment of endometrial carcinoma and breast cancer, is currently administered orally as a solid dosage form. Bioavailability of the drug following oral administration is closely related to the effectiveness and safety profile of the drug in formulation. Improved immediate-release formulations should allow improved drug delivery into the systemic circulation and, at the end, to the site of action. The micronization of drugs is one of the technological procedures to achieve such a purpose. This paper reports the design and results obtained in an in vivo study of the bioavailability of a micronized megestrol acetate tablet formulation compared to a conventional form. A significant increase in the drug bioavailability was observed, in either the rate or the extent of absorption. In vitro dissolution data of the two study formulations reflected the in vivo findings.     

Nanoemulsions as delivery systems for lipophilic drugs

Nanoemulsions have received a growing attention as colloidal drug carriers for pharmaceutical applications. Their advantages over conventional formulations include drug enhanced solubility and bioavailability, protection from toxicity, improved pharmacological activity and stability, more sustained delivery and protection from physical and chemical degradation. Nanoemulsions can be prepared by two major techniques, high-energy and low-energy emulsification. Both these emulsification methods have proved to be efficient to obtain stable nanoemulsions with small and highly uniform droplets. Further research into nanoemulsions is important to develop novel liquid formulations with more efficient results in therapeutic.     

Recent advances in ocular drug delivery

Amongst the various routes of drug delivery, the field of ocular drug delivery is one of the most interesting and challenging endeavors facing the pharmaceutical scientist. Recent research has focused on the characteristic advantages and limitations of the various drug delivery systems, and further research will be required before the ideal system can be developed. Administration of drugs to the ocular region with conventional delivery systems leads to short contact time of the formulations on the epithelium and fast elimination of drugs. This transient residence time involves poor bioavailability of drugs which can be explained by the tear production, non-productive absorption and impermeability of corneal epithelium. Anatomy of the eye is shortly presented and is connected with ophthalmic delivery and bioavailability of drugs. In the present update on ocular dosage forms, chemical delivery systems such as prodrugs, the use of cyclodextrins to increase solubility of various drugs, the concept of penetration enhancers and other ocular drug delivery systems such as polymeric gels, bioadhesive hydrogels, in-situ forming gels with temperature-, pH-, or osmotically induced gelation, combination of polymers and colloidal systems such as liposomes, niosomes, cubosomes, microemulsions, nanoemulsions and nanoparticles are discussed. Novel ophthalmic delivery systems propose the use of many excipients to increase the viscosity or the bioadhesion of the product. New formulations like gels or colloidal systems have been tested with numerous active substances by in vitro and in vivo studies. Sustained drug release and increase in drug bioavailability have been obtained, offering the promise of innovation in drug delivery systems for ocular administration. Combining different properties of pharmaceutical formulations appears to offer a genuine synergy in bioavailability and sustained release. Promising results are obtained with colloidal systems which present very comfortable conditions of use and prolonged action.     

Lipid nanoparticles of zaleplon for improved oral delivery by Box–Behnken design: optimization,in vitro and in vivo evaluation

Purpose: Zaleplon (ZL) is a hypnotic drug prescribed for the management of insomnia and convulsions. The oral bioavailability of ZL was low (～30%) owing to poor water solubility and hepatic first-pass metabolism. The cornerstone of this investigation is to develop and optimize solid lipid nanoparticles (SLNs) of ZL with the aid of Box–Behnken design (BBD) to improve the oral bioavailability.

Methods: A design space with three formulation variables at three levels were evaluated in BBD. Amount of lipid (A₁), amount of surfactant (A₂) and concentration of co-surfactant (%) (A₃) were selected as independent variables, whereas, particle size (B₁), entrapment efficiency (B₂) and zeta potential (ZP, B₃) as responses. ZL-SLNs were prepared by hot homogenization with ultrasonication method and evaluated for responses to obtain optimized formulation. Morphology of nanoparticles was observed under SEM. DSC and XRD studies were examined to understand the native crystalline behavior of drug in SLN formulations. Further, in vivo studies were performed in Wistar rats.

Results: The optimized formulation with 132.89?mg of lipid, 106.7?mg of surfactant and 0.2% w/v of co-surfactant ensued in the nanoparticles with 219.9?±?3.7?nm of size, ?25.66?±?2.83?mV surface charge and 86.83?±?2.65% of entrapment efficiency. SEM studies confirmed the spherical shape of SLN formulations. The DSC and XRD studies revealed the transformation of crystalline drug to amorphous form in SLN formulation. In conclusion, in vivo studies in male Wistar rats demonstrated an improvement in the oral bioavailability of ZL from SLN over control ZL suspension.

Conclusions: The enhancement in the oral bioavailability of ZL from SLNs, developed with the aid of BBD, explicated the potential of lipid-based nanoparticles as a potential carrier in improving the oral delivery of this poorly soluble drug.     

Development of novel amisulpride-loaded liquid self-nanoemulsifying drug delivery systems via dual tackling of its solubility and intestinal permeability

Objective: The aim of the current investigation was at enhancing the oral biopharmaceutical behavior; solubility and intestinal permeability of amisulpride (AMS) via development of liquid self-nanoemulsifying drug delivery systems (L-SNEDDS) containing bioenhancing excipients.

Methods: The components of L-SNEDDS were identified via solubility studies and emulsification efficiency tests, and ternary phase diagrams were constructed to identify the efficient self-emulsification regions. The formulated systems were assessed for their thermodynamic stability, globule size, self-emulsification time, optical clarity and in vitro drug release. Ex vivo evaluation using non-everted gut sac technique was adopted for uncovering the permeability enhancing effect of the formulated systems.

Results: The optimum formulations were composed of different ratios of Capryol? 90 as an oil phase, Cremophor^® RH40 as a surfactant, and Transcutol^® HP as a co-surfactant. All tested formulations were thermodynamically stable with globule sizes ranging from 13.74 to 29.19?nm and emulsification time not exceeding 1?min, indicating the formation of homogenous stable nanoemulsions. In vitro drug release showed significant enhancement from L-SNEDDS formulations compared to aqueous drug suspension. Optimized L-SNEDDS showed significantly higher intestinal permeation compared to plain drug solution with nearly 1.6–2.9 folds increase in the apparent permeability coefficient as demonstrated by the ex vivo studies.

Conclusions: The present study proved that AMS could be successfully incorporated into L-SNEDDS for improved dissolution and intestinal permeation leading to enhanced oral delivery.