Melt Emulsification Research Articles

Statistical Sequential Experimentation: Preliminary Mixed Factorial Design, I-Optimal Mixture Design Then Finally Novel Design Space Expansion for Optimization of Tazarotene Cubosomes.

ObjectiveThis study aims to illustrate the potential of sequential experimentation for statistically scientific based optimization of Tazarotene (TAZA) cubosomes.MethodsHot melt emulsification method was used for cubosomes preparation. A preliminary (3.2) mixed factorial design (MFD) was conducted to choose suitable types of stabilizer and surfactant that maximize entrapment efficiency (EE) and minimize particle size (PS). These chosen stabilizer and surfactant were to be used in the statistical design proposed for optimization of TAZA cubosomes (I-optimal mixture design) (IOMD). Glyceryl monooleate (GMO), stabilizer and surfactant amounts were the three mixture components (MixCs) studied in that design. Responses (EE, PS and drug percent released after 24 hours (Q24h)) were statistically analyzed. Numerical optimization using desirability function based on different responses’ importance was used to find an IOMD-optimized formulation (IOMD-OF) with the predetermined characters. Then, a novel statistical methodology of design space expansion was adopted to enhance Q24h. Suitable models to express EE, PS and Q24h were elucidated over the expanded mixture design (EMD) space. Validity of derived models was verified via prediction intervals and percent deviations of actual values from predicted ones for all the EMD design points. EMD was then navigated to find EMD-OF.ResultsAnalysis of MFD showed that Pluronic-F68 and polyvinyl alcohol were the best stabilizer and surfactant to be used. First stage optimization after IOMD analysis led to a formulation with unsatisfactory Q24h of 58.8%. After design space expansion adoption, re-analysis and re-optimization, a satisfactory EMD-OF having EE of 82.1%, PS of 273.0 nm and Q24h of 68.8% was found.ConclusionStatistical sequential experimentation with the novel design space expansion approach proved to be a successful paradigm for enhancing TAZA cubosomes optimization. Thus, this paradigm is expected to have promising future applications in various pharmaceutical formulations optimization.

Susceptibility of Lung Carcinoma Cells to Nanostructured Lipid Carrier of ARV-825, a BRD4 Degrading Proteolysis Targeting Chimera.

The present work was aimed at developing an optimized and modified nanostructured lipid carrier of BRD4 protein degrading Proteolysis Targeting Chimera (PROTAC) against non-small cell lung carcinoma. PROTACs are an emerging class of anticancer molecules with nanomolar activity but associated with significant solubility challenges. Lipid-based colloidal systems like nanostructured lipid carriers are widely explored for such highly lipophilic molecules. ARV-825, a cereblon-based PROTAC was investigated for its anticancer efficacy in vitro in 2D and 3D lung cancer models. ARV-825 loaded PEGylated nanostructured lipid carriers (AP-NLC) was prepared using melt emulsification technique. ARV-825 was stabilized using Precirol® ATO5 and Captex® 300 EP/NF as the solid and liquid lipid, respectively. However, hydrophobic ion-pairing with medium chain fatty acid was required to improve drug loading and stability. A hydrodynamic diameter and polydispersity index of 56.33 ± 0.42nm and 0.16 respectively with zeta potential of -21 ± 1.24mV was observed. In vitro migration and colony formation assay confirmed the anticancer activity of ARV-825 alone and AP-NLC. Nearly 38% and 50% apoptotic cell population were observed after ARV-825 and AP-NLC treatment. Immunoblotting assay showed complete suppression of BRD4 and c-Myc protein expression for AP-NLC. Most importantly, significant reduction in the growth of multicellular 3D spheroid of A549 cells confirmed the effectiveness of BRD4 PROTAC and its lipid nanoparticle in non-small cell lung cancer (NSCLC). AP-NLC. Higher amount of red fluorescence throughout the spheroid surface further confirmedsuperior efficacy of AP-NLC in tumor penetration and cell killing.

Nanostructured lipid carrier for transdermal gliclazide delivery: development and optimization by Box-Behnken design

The aim of current study was to prepare and optimize the nanostructured lipid carrier (NLC) for transdermal gliclazide (GCZ) delivery. The melt emulsification followed by ultrasonication technique was utilized to prepare GCZ–loaded-NLC. The optimization of NLC was achieved by Box-Behnken design. The surfactant (Tween 20) % (X1), total lipid (glyceryl monostearate + Lauroglycol™ 90) % (X2), and sonication time (min) (X3) were chosen as independent variables, while particles size (Y1), polydispersity index (Y2), and entrapment efficiency (Y3) were selected as response. Further, the prepared NLC was estimated for in vitro drug release study, ex vivo skin permeation and confocal laser scanning microscopy (CLSM) studies. Results of present study demonstrated that the optimized GCZ loaded NLC formulation presented the particles size, polydispersity index, zeta potential, and entrapment efficiency of 120.4 nm, 0.316, −5.58 mV, and 87.32% respectively. The in vitro drug release study indicated drug release of 68.27 ± 2.98% and 45.87 ± 2.85% for GCZ-NLC and conventional GCZ dispersion respectively. The GCZ-NLC-Gel formulation exhibited transdermal drug permeation of 76.89 ± 2.52% as compared to conventional gel (45.65 ± 2.79%). The CLSM of rat skin treated with NLC gel exhibited a deeper permeation (35 μm) in comparison to the conventional gel (15 μm). In conclusion, GCZ loaded NLC was successfully optimized using Box-Behnken design that contributed many advantages over conventional formulation and thus demonstrating NLC as propitious carriers for the transdermal GCZ delivery.

Production of spherical ester wax powders by melt emulsification for Additive Manufacturing

Powder bed fusion of polymers with laser beam (PBF-LB/P) involves selectively melting plastic micro particles with a laser and building up the parts layer by layer, which offers great freedom of design. However, the choice of commercially available thermoplast feedstock powders is limited (90% polyamides). In order to extend the range of materials, this contribution presents the production of highly spherical micro particles by melt emulsification followed by spray agglomeration for ester wax. The effect of process parameters during emulsification (energy input, surfactant to polymer ratio) on the particle size distribution is demonstrated in detail for the ester wax system. In order to generate and tune particle sizes to a range suitable for PBF, melt emulsified ester wax dispersions are spray agglomerated. Agglomerated ester wax powders were used for the PBF process to manufacture tensile strength specimens type 5A.

Emerging Implementation of Nano-Suspension Technology for Delivery of Poorly Soluble Drug for the Treatment of Helminths Disease

Anthelmintics are medications that are used to treat parasitic worm infections. This comprises flat worms like flukes and tapeworms as well as round worms like nematodes. They are critical for human tropical medicine. Nano-suspensions are one of the many applications of nanotechnology. Nano-suspensions are liquid formulations that feature submicron colloidal dispersion of pharmaceutical active component particles stabilised by surfactants. Nano-suspension technology is a novel and cost-effective method for improving the bioavailability of hydrophobic medicines, particularly those that are poorly soluble in aqueous solutions. Nano-suspensions play a significant role in the development of new medication formulations. High pressure homogenizers, emulsion solvent evaporation, melt emulsification technique, and nanoprecipitation are all used to make nano-suspensions. Particle size, zeta potential, drug content, and in vitro drug dissolution were all examined for the nano-suspensions. Poorly soluble drugs can benefit from nano-suspension technology to improve their stability and bioavailability. The bioavailability of nano-suspension was also tested in mice, which showed that the particle size distribution of nano-suspension was considerably affected by bioavailability. The rate of anthelmintic nano-suspension dissolution was substantially higher than that of raw drug powder. In vivo pharmacokinetic characteristics of nano-suspension indicated a substantial increase in Cmax and AUC(0-t) when compared to pure drug. When compared to pure drug bioavailability, anthelmintic nano-suspension had a greater oral bioavailability.

Solvent-Free Fabrication of Biphasic Lipid-Based Microparticles with Tunable Structure

Lipid-based biphasic microparticles are generally produced by long and complex techniques based on double emulsions. In this study, spray congealing was used as a solvent-free fabrication method with improved processability to transform water-in-oil non-aqueous emulsions into spherical solid lipid-based particles with a biphasic structure (b-MPs). Emulsions were prepared by melt emulsification using different compositions of lipids (Dynasan®118 and Compritol®888 ATO), surfactants (Cetylstearyl alcohol and Span®60) and hydrophilic carriers (PEGs, Gelucire®48/16 and Poloxamer 188). First, pseudo-ternary phase diagrams were constructed to identify the area corresponding to each emulsion type (coarse emulsion or microemulsion). The hydrophobicity of the lipid mostly affected the interfacial tension, and thus the microstructure of the emulsion. Emulsions were then processed by spray congealing and the obtained b-MPs were characterized in terms of thermal and chemical properties (by DSC and FT-IR), external and internal morphology (by SEM, CLSM and Raman mapping). Solid free-flowing spherical particles (main size range 200–355 µm) with different architectures were successfully produced: microemulsions led to the formation of particles with a homogeneous internal structure, while coarse emulsions generated “multicores-shell” particles consisting of variable size hydrophilic cores evenly distributed within the crystalline lipid phase. Depending on their composition and structure, b-MPs could achieve various release profiles, representing a more versatile system than microparticles based on a single lipid phase. The formulation and technological strategy proposed, provides a feasible and cost-effective way of fabricating b-MPs with tunable internal structure and release behavior.

Sustained vaginal delivery of in situ gel containing Voriconazole nanostructured lipid carrier: formulation, in vitro and ex vivo evaluation

Voriconazole (VOZ) is an antifungal drug having poor aqueous solubility. VOZ nanostructured lipid carrier (VNLC) was prepared by using melt emulsification followed by ultrasonication technique. The VNLCs were optimized by 32 full factorial design using Design-Expert® software. The optimized VNLC had a particle size, zeta potential and entrapment efficiency of 205.8 nm, −27.1 mV and 78.85%, respectively. The optimized VNLC was further loaded in thermosensitive in situ gel. In vitro release studies of VNLC gel showed sustained release of the drug (98.84 ± 1.26%) for up to 24 h. The ex vivo permeation studies showed higher penetration for the VNLC gel as compared to plain VOZ gel. The in vitro antifungal assay showed higher efficacy of VNLC than that of plain VOZ. The HET-CAM test of the VNLC gel showed no irritation and thus was found to be suitable for vaginal administration. Thus, it can be concluded that the developed VNLC gel showed a sustained release pattern with higher drug localization in the vaginal tissue and thus can offer improved treatment of vaginal candidiasis.

Design of Lipid Nanoparticles Containing Fenugreek Seed Extract

Background: The main purpose of this study was to maximize the efficacy of fenugreek seed extract by loading it in an optimised solid lipid nanoparticles (SLNs) formula.
 Methods: To achieve an effective extraction method, preliminary studies were carried out to confirm the extract, and the extract was standardised using trigonelline. The influence of independent variables lipid concentration (X1), surfactant concentration (X2), and cosurfactant concentration (X3) on dependent variables particle size (Y1) and entrapment efficiency (Y2) was also studied and optimised using the Box–Behnken design. Melt emulsification followed by ultrasonication was used to prepare SLN formulations. To understand the effect of independent variables on the dependent quality parameters, response surface plots and mathematical equations were produced.
 Results: The results confirmed that soxhalation was the most suitable method for extraction of fenugreek seeds, confirmed by standardization. Further optimization revealed that particle sizes ranged from 193.4 to 312.3 nm, with entrapment efficiencies ranging from 61.2 to 74.32 percent. This implies that the developed formulations can be used for further in vitro and in vivo characterizations.

The Emerging Role of Nanosuspensions for Drug Delivery and Stability

: Poor solubility of some medicinal compounds is a serious challenge that can be addressed by using a nano-suspension for improved delivery. The nanoparticles enhance the bioavailability along with the aqueous solubility of the drug, which is accomplished by increasing the active surface area of the drug. The gained attention of the nanosuspension is due to its stabilization facility, which is achieved by polymers, such as polyethylene glycol (PEG), having a particular size range of 10 - 100 nm. Hence, these nanoparticles have the capacity of binding to the targeted with very low damage to the healthy tissues. These are prepared by various methods, such as milling, high-pressure homogenization, and emulsification, along with melt emulsification. Moreover, surface modification and solidification have been used to add specific properties to the advanced therapies as post-processing techniques. For many decades, it has been known that water solubility hampers the bioavailability and not all drugs are water-soluble. In order to combat this obstacle, nanotechnology has been found to be of specific interest. For elevating the bioavailability by increasing the dissolution rate, the methodology of reduction of the associated drug particles into their subsequent submicron range is incorporated. For oral and non-oral administration, these nanosuspension formulations are used for the delivery of drugs.

Solid nanostructured lipid carriers loaded with silymarin for oral delivery: Formulation development and evaluation

The present study was aimed at preparing stable dry adsorbed nanoparticles (DANs) of silymarin loaded nanostructured lipid carriers (NLCs). The prepared silymarin loaded NLCs and DANs were characterized for various quality parameters. Silymarin loaded NLCs were prepared by a modified hot melt emulsification ultra-sonication method using glyceryl monostearate (GMS), capmul MCM C8 EP (CAP) and gelucire 50/13 (G50/13) as solid lipid, liquid lipid and surfactant respectively. For better stability, NLC dispersion was converted into DANs by adsorbing them onto some suitable carriers. NLCs and DANs were characterized for particle size, polydispersity index, zeta potential, entrapment efficiency, drug loading, assay, thermal behavior, crystallinity and morphological study. The optimized NLCs have a mean particle size of 206.1±012.5 nm (size distribution of 0.249±0.058), a zeta potential of -32.5±1.2 mV with high entrapment of 95.60±0.45% and drug loading of 1.90±0.08%. The X-ray diffraction and endothermic peaks confirmed the maximum encapsulation of active in lipid matrices. The particles were spherical with smooth surface morphology. In-vitro release studies showed sustained drug release for up to 24 h. Ex-vivo permeation in the presence and absence of lymphatic blocker indicates the uptake of silymarin loaded NLCs by the lymphatic route. Silymarin loaded NLCs prepared had a nanosize distribution with high entrapment efficiency. The ex-vivo permeation study for optimized NLC formulation exhibited the lymphatic uptake of active. Dispersion stability was increased by preparing the DANs. The solid dry powder is used for oral reconstitution and can be further converted into tablets or filled into capsules.

SURFACE MODIFIED NANOSTRUCTURED LIPID CARRIER FOR IMPROVED OCULAR DELIVERY: IN VITRO AND EX-VIVO STUDY

Nano structured lipid carrier (NLC) is a new generation Nano particulate system that offers several advantages over polymeric nanoparticles. However, NLC possesses less muco-adhesiveness in the eye due to its anionic nature. Therefore, the present study aimed to modify the surface of NLC with cationic compounds to improve corneal permeability. The objective of the present study was to prepare and optimize Dexamethasone NLC, surface modification of NLC with carboxymethyl chitosan, and comparative evaluation of both with the marketed formulation. A combined melt emulsification and ultrasonication method was used to prepare NLC. The optimized NLC formulations shown particle size (64±2.3 nm), polydispersity in Dexamethasone (0.270±0.008), zeta potential (-12±3.42 mV), and entrapment efficiency (96.66±0.41%). Carboxymethyl chitosan modified dexamethasone loaded NLC showed particle size (260.73±4.66 nm) and dexamethasone (10.8±6.0 mV). It exhibited sustained drug release than NLC and marketed eye drop. In the ex vivo study, surface modified NLC had a permeability coefficient of 228.88 cm h-1, which is 2.60-and 1.61-times greater than eye drop and NLC, respectively. Surface-modified NLC has shown comparatively sustained release with plain NLC and commercial eye drops. The surface-modified form can adhere firmly with mucin and shown improved trans corneal permeability. Therefore, CNLC would be the potential nanocarrier for dexamethasone to minimize dose requirement and overcome systemic adverse events.

SURFACE MODIFIED NANOSTRUCTURED LIPID CARRIER FOR IMPROVED OCULAR DELIVERY: IN VITRO AND EX-VIVO STUDY

Nano structured lipid carrier (NLC) is a new generation Nano particulate system that offers several advantages over polymeric nanoparticles. However, NLC possesses less muco-adhesiveness in the eye due to its anionic nature. Therefore, the present study aimed to modify the surface of NLC with cationic compounds to improve corneal permeability. The objective of the present study was to prepare and optimize Dexamethasone NLC, surface modification of NLC with carboxymethyl chitosan, and comparative evaluation of both with the marketed formulation. A combined melt emulsification and ultrasonication method was used to prepare NLC. The optimized NLC formulations shown particle size (64±2.3 nm), polydispersity in Dexamethasone (0.270±0.008), zeta potential (-12±3.42 mV), and entrapment efficiency (96.66±0.41%). Carboxymethyl chitosan modified dexamethasone loaded NLC showed particle size (260.73±4.66 nm) and dexamethasone (10.8±6.0 mV). It exhibited sustained drug release than NLC and marketed eye drop. In the ex vivo study, surface modified NLC had a permeability coefficient of 228.88 cm h-1, which is 2.60-and 1.61-times greater than eye drop and NLC, respectively. Surface-modified NLC has shown comparatively sustained release with plain NLC and commercial eye drops. The surface-modified form can adhere firmly with mucin and shown improved trans corneal permeability. Therefore, CNLC would be the potential nanocarrier for dexamethasone to minimize dose requirement and overcome systemic adverse events.

Nose to Brain Delivery of Phenytoin Sodium Loaded Nano Lipid Carriers: Formulation, Drug Release, Permeation and In Vivo Pharmacokinetic Studies.

An acute epileptic seizure is a seizure emergency fatal condition that requires immediate medical attention. IV phenytoin sodium remains the second line therapeutic agent for the immediate treatment of status epilepticus. Phenytoin sodium formulated as nanolipid carriers (NLCs) seems to be promising as an intranasal delivery system for controlling acute seizures. Three different nanosized phenytoin sodium loaded NLCs (<50 nm, 50–100 nm and >100 nm) were prepared by melt emulsification and was further characterised. In vitro drug release studies showed immediate drug release from phenytoin sodium loaded NLCs of <50 nm size, which is highly essential for acute seizure control. The ex vivo permeation study indicated greater permeation from <50 nm sized NLC through the olfactory epithelium compared to thecontrol drug solution. Invivo pharmacokinetic studies revealed higher drug concentration in CSF/brain within 5 min upon intranasal administration of <50 nm sized phenytoin sodium NLCs than the control drug solution and marketed IV phenytoin sodium, indicating direct and rapid nose to brain drug transport through the olfactory epithelium. The study has shown that formulation strategies can enhance olfactory uptake, and phenytoin sodium NLCs of desired particle sizes (<50 nm) offer promising potential for nose to brain direct delivery of phenytoin sodium in treating acute epileptic seizures.

Formulation, characterization, and pharmacokinetic evaluation of Ivabradine-Nebivolol co-encapsulated lipospheres

A Central Composite Rotatable Design (CCRD) was applied to statistically optimized lipospheres (LS) formulated for enhancing the pharmacokinetics of co-administered Ivabradine and Nebivolol as well as improving the patients’ compliance. The lipospheres (LS) were prepared by simple melt emulsification technique and impact of formulation variables (Carnauba wax, Beeswax, and surfactant) on percentage yield (Y1), IVB-release (Y2) and NEB-release (Y3) was statistically investigated. The numerical optimization technique was adopted to select optimized lipospheres (OL) which were then subjected to a comparative in vivo pharmacokinetic analysis against commercially available brands. The physicochemical analysis of LS was performed by FTIR, DSC and x-ray powder diffractometry (XRD). Lipospheres were also analysed for micromeritics, zeta potential, size, and morphology. The spherical, smooth surface, free-flowing LS having zeta potential of −40 to −60 mV and size-range of 10–50 µm were successfully formulated. The physicochemical analysis demonstrated a complete lack of drugs interaction with lipids carriers, and p-XRD showed a transformation of crystalline drugs to amorphous form. The outcomes for Y1 (38–88%), IVB-release (47–96%) and NEB-release (38–88%) followed polynomial quadratic model. The pharmacokinetics analysis of LS showed a significantly decreased Cmax of IVB (39.29 ± 6.39), NEB (56.69 ± 3.73) with an effectively raised Tmax (13.41 h for IVB and 14.53 h for NEB) as compared to IVB (49.67 ± 5.26 ng/mL) and NEB (71.32 ± 4.57 ng/mL) of commercial brands. Moreover, an expressively increased half-life (17hr for IVB, 19 hr for NEB), AUC0-24 (8121 for IVB, 11,368 for NEB) and mean residence time for IVB and NEB indicated the accomplishment of greater bioavailability of drugs released from LS. Conclusively, such an innovative idea of combination loaded LS of IVB, and NEB would convincingly bring an effective management of chronic cardiovascular complications by maintaining the plasma drugs concentration for a prolonged time.

FORMULATION AND QBD BASED OPTIMIZATION OF METHOTREXATE-LOADED SOLID LIPID NANOPARTICLES FOR AN EFFECTIVE ANTI-CANCER TREATMENT

Objective: In the current study, the Quality by Design method was utilized for the formulation of solid lipid nanoparticles of Methotrexate (MTX SLNs). Methods: MTX SLNs formulated by melt emulsification method were studied for the effect of independent variables viz. concentration of lipid and surfactants on quality attributes viz. particle size, polydispersity index, and entrapment efficiency of SLNs using 32 factorial design. Results: The optimal formulation was spherical, had a particle size of 147.6±4.1 nm (z-average), a polydispersity index of 0.296±0.058, a zeta potential of −19±0.98 mV, encapsulation efficiency of 98.7±1.55%, and a cumulative drug release of 95.59±0.918% in 5 h. Conclusion: The in vitro and in vivo studies revealed that SLNs provide a promising oral delivery system to improve the bioavailability of MTX.

Topical Delivery of Fenugreek Seed Extract Loaded Solid Lipid Nanoparticles Based Hydrogels for Alopecia

Background: Alopecia, a chronic dermatological inflammatory condition affecting the hair follicles. Conventional treatments are associated with the risk of serious side effects. The stratum corneum limits the percutaneous absorption of drugs. Hence, the development of novel herbal formulations for topical delivery has been the target, with the enhancement of their therapeutic efficacy and safety of use.&#x0D; Aims: To formulate and characterize Fenugreek seed extract loaded solid lipid nanoparticles carrier for the management of Alopecia to reduce the systemic side effects.&#x0D; Methodology: Fenugreek seed extract loaded solid lipid nanoparticles (SLN) were prepared by melt emulsification accompanied by probe sonication. The formulation was prepared using GMS, Tween 80, and Soya lecithin as Lipid, Surfactant, and Co-Surfactant. The SLN was incorporated into carbapol 934 dispersion to convert it into a gel. The SLN formulation was evaluated for size, Polydispersity Index, Zeta Potential, Entrapment efficiency, Transmission Electron Microscopy. After that, the SLN gel was examined for Spreadability, Extrudabilty, Viscosity, In vitro drug release, Ex vivo permeation, and Skin deposition studies.&#x0D; Results: The formulated Fenugreek seed extract loaded showed a particle size of 223.36 nm with a narrow PDI of 0.313. Entrapment efficiency revealed that 74.56±0.12% of the drug was entrapped. Transmission electron microscopy images confirmed the spherical nature of the SLN. The extended-release pattern of the formulated SLN for 24h was observed in the in vitro release studies and followed Higuchi model(R2=0.9964). Ex vivo permeability showed a 72.05±0.15% deposition of Fenugreek seed extract loaded SLN. The formulation was stable for three months without significant changes.&#x0D; Conclusion: Fenugreek seed extract loaded NLC demonstrated enhanced permeation, improved skin retention, and extended release compared to conventional gel. The developed formulation would be further used for in vivo studies and by seeing above results it can be an alternative for Alopecia in the future.

Design and optimization of curcumin loaded nano lipid carrier system using Box-Behnken design

Herbal antioxidant like curcumin holds great potential to treat neurodegenerative disease like Alzheimer's disease. However, its therapeutic potency is obstructed due to rapid metabolism, poor solubility, GI susceptibility, enzymatic degradation and lower bioavailability. Thus, the present work aimed to design and optimize curcumin-loaded NLC (CNL) with higher drug entrapment, prolonged release and better stability. CNL was prepared by modified melt emulsification method followed by ultrasonication. The formulation was optimized by 3 factor 3 level Box-Behnken design using solid: liquid lipid, surfactant concentration and ultrasonication time as independent variable while particle size, entrapment efficiency and % drug release as dependant variable. The design suggested 3.092 solid:liquid lipid, 2.131% surfactant and 4.757 min ultrasonication fit best to get the optimized formulation. The size of the optimized CNL was noted 124.37 ± 55.81 nm, which is in the acceptable range for brain delivery. SEM results also comply with this size range (near 150 nm) and demonstrated almost spherical and uniform particles with porous and uneven surface structures. PDI, zeta potential, entrapment efficiency and % drug release were observed as 0.201 ± 0.00, − 17.2 ± 2.35 mV, 93.62 ± 0.68% and 92.73 ± 0.06%, respectively. The NLC demonstrated initial burst release with subsequent prolonged release of drug for 48 h. Weibull kinetic equation with 0.9958 R2, minimum AIC and maximum MSC value was found best fit to explain the release behavior. The β exponent and diffusional coefficient (n) indicated combined release mechanism with Fickian diffusion as drug release mechanism. Formulation was also found stable at different storage condition.

Nanostructured Lipid Carrier (NLC) and Solid Lipid Nanoparticles (SLN) Based Hydrogel for Delivery of Etodolac: A Comparative Investigation on Dermal Pharmacokinetic on Rat Skin

Objectives: The present work focus on to create Solid lipid nanoparticles (SLN) and nanostructured lipid Carrier (NLC) as transporters for effective delivery of Etodolac (ETD). Methods: Etodolac stacked SLN and NLC were set up by melting emulsification and hardening at low temperature method and they were portrayed for molecule size, zeta potential, encapsulation efficacy and in vitro discharge rate. Ex vivo dermatokinetic by tape stripping technique was explored in rat skin utilizing altered Franz diffusion cells. The praticle size and the surface electrical charge (ZP) have been assessed following after manufacturing of dispersion. Results: The particles stayed in their colloidal range after production by melt emulsification method. For all nano dispersion the encapsulation efficacy was higher than 75%. Differential Scanning calorimetry (DSC) were performed to portray the physicochemical properties of the SLN and NLC. Approximately Same amount of Etodolac release was facilitated through skin of rats from SLN-SA and NLC-SA. Conclusion: Research work could be concluded as successful development of Etodolac loaded SLN and NLC to increase the encapsulation efficiency of colloidal lipid carriers with benefit of higher performance in terms of long term stability and impart a sustaining Etodolac topical effect as well as faster relief from pain associated with arthritis.

Fabrication and evaluation of Lambda-Cyhalothrin nanosuspoemulsion with pH- and temperature-responsive based on polyethylene wax as carrier

Using polyethylene wax (PW) as the coating matrix, the lambda-cyhalothrin-PW nanosuspoemulsion (LC-PW) with a particle size of 80-150nm was prepared through high-speed stirring, hot melt emulsification and ultrasonic dispersion. The formulation and composition of the LC-PW were optimized, the morphology of the LC-PW was analyzed by dynamic light scattering (DLS) and TEM, and the structure of the LC-PW was characterized by UV and IR. The anti-photolysis test showed that LC-PW had a good anti-photolysis performance. Furthermore, LC-PW could sustainably release Lambda-cyhalothrin, which was pH- and temperature dependent. The insecticidal activity analysis in the greenhouse indicated that the toxic strength between LC-PW and LC-SC (lambda-cyhalothrin-suspension concentrate) to Mythimna separata was similar within the same concentration ranges tested, but the insecticidal duration of LC-PW was significantly longer than LC-SC. Thus, the new type of LC-PW with the properties of anti-photolysis and controlled release is suitable for application in the field as a better insecticide.

Topical Delivery of Apremilast Loaded Nanostructured Lipid Carrier Based Hydrogel for Psoriasis Therapy

Background: Apremilast (APR) is an orally administered selective phosphodiesterase 4 inhibitor approved to treat plaque psoriasis and psoriatic arthritis and is available as an oral tablet formulation. However, its systemic side effects limit its application. The low solubility and permeability of apremilast make it difficult to administer it through the skin. Hence an attempt is made to incorporate apremilast into a suitable nanocarrier to facilitate its topical delivery.&#x0D; Aims: To formulate and characterize Apremilast loaded nanostructured lipid carriers for the management of psoriasis to reduce the systemic side effects.&#x0D; Methodology: Apremilast loaded Nanostructured Lipid carriers (NLC) were prepared by melt emulsification accompanied by probe sonication. The formulation was prepared using GMS, Sefsol 218, Tween 80 and Transcutol P as Solid Lipid, Liquid lipid, Surfactant and Penetration Enhancer. The NLC was incorporated into carbapol 934 dispersion to convert it into a gel. The NLC formulation was evaluated for size, Polydispersity Index, Zeta Potential, Entrapment efficiency, Transmission Electron Microscopy. After that, the NLC gel was examined for Spreadability, Extrudabilty, Viscosity, In vitro drug release, Ex vivo permeation, Skin deposition and In vivo studies.&#x0D; Results: The formulated Apremilast loaded showed particle size of less than 200 nm (i.e.170.32nm) with a narrow PDI of 0.267. Entrapment efficiency revealed that 89.26±01.22% of the drug was entrapped. Transmission electron microscopy images confirmed the spherical nature of the nanocarrier. The extended-release pattern of the formulated NLC for 24h was observed in the in vitro release studies and followed the Higuchi model(R2=0.9966). Ex vivo permeability showed a 6.14 fold increase in permeability and 74.05±0.25% deposition of apremilast loaded NLC gel compared to apremilast gel. The formulation was stable for three months without significant changes. In vivo skin studies showed that the prepared NLC did not have any skin irritation potential. The antipsoriatic activity demonstrated by the Apremilast loaded NLC gel in the imiquimod induced psoriasis model in mice was comparable to the standard treatment.&#x0D; Conclusion: Apremilast loaded NLC demonstrated enhanced permeation, improved skin retention and extended-release compared to conventional gel. The developed formulation can be an alternative for psoriasis therapy after clinical trials in the future.