Solid super saturated self-nanoemulsifying drug delivery system (sat-SNEDDS) as a promising alternative to conventional SNEDDS for improvement rosuvastatin calcium oral bioavailability

ABSTRACT

Objective: This study aims to illustrate the applicability of solid supersaturated self-nanoemulsifying drug delivery system (sat-SNEDDS) for the improvement of rosuvastatin calcium (RC) oral bioavailability.

Methods: Different sat-SNEDDS were prepared by incorporating different ratios of RC into SNEDDS using tween80/PEG400 (77.2%) as surfactant/cosurfactant mixture and garlic /olive oil (22.8%) as oil phase. The prepared systems were characterized viz; size, zeta potential, TEM and stability. Various hydrophilic and hydrophobic carriers were employed to solidify the optimized RC sat-SNEDDS. The influence of the carrier was investigated by SEM, XRPD, DSC, flow properties, in vitro precipitation, drug release and oral bioavailability study.

Results: The adsorption of the stable positively charged nanocarrier RC sat-SNEDDS onto solid carriers provided free flowing amorphous powder. The carrier could amend the morphological architecture and in vitro release of the RC solid sat-SNEDDS. Hydrophobic carriers as microcrystalline cellulose 102 (MCC) showed superior physical characters and higher dissolution rate over hydrophilic carriers as maltodextrin with respective T_100% 30 min and 45 min. The rapid spontaneous emulsification, the positively nanosized MCC-sat-SNEDDS improved oral bioavailability of RC by 2.1-fold over commercial tablets.

Conclusion: Solid MCC-sat-SNEDDS combined dual benefits of sat-SNEDDS and solid dosage form was successfully optimized to improve RC oral bioavailability.     

Effects of solid carriers on the crystalline properties, dissolution and bioavailability of flurbiprofen in solid self-nanoemulsifying drug delivery system (solid SNEDDS)

In order to investigate the effects of solid carriers on the crystalline properties, dissolution and bioavailability of flurbiprofen in a solid self-nanoemulsifying drug delivery system (solid SNEDDS), different solid SNEDDS formulations were prepared by spray-drying the solutions containing liquid SNEDDS and various carriers. The liquid SNEDDS, composed of Labrafil M 1944 CS/Labrasol/Trasncutol HP (12.5/80/7.5%) with 2% w/v flurbiprofen, gave a z-average diameter of about 100 nm. Silicon dioxide, a hydrophobic solid carrier, produced an excellent conventional solid SNEDDS with a nanoemulsion droplet size of less than 100 nm, similar to the liquid SNEDDS and smaller than the other solid SNEDDS formulations. The drug was in an amorphous state in this solid SNEDDS. Furthermore, it greatly improved the dissolution rate and oral bioavailability of flurbiprofen in rats because it allowed the spontaneous formation of an interface between the oil droplets and the water. Magnesium stearate, a hydrophobic carrier, produced a solid SNEDDS with the largest diameter. However, it greatly enhanced the dissolution rate and oral bioavailability due to the formation of a simple eutectic mixture. The hydrophilic carriers such as polyvinyl alcohol (PVA), sodium carboxymethyl cellulose (Na-CMC) and hydroxypropyl-β-cyclodextrantrin (HP-β-CD) did not form a solid SNEDDS but rather a solid dispersion (or microcapsule). HP-β-CD improved the dissolution rate but did not improve the oral bioavailability as much as the hydrophobic polymers. PVA and Na-CMC hardly improved the dissolution rate but maintained constantly high plasma levels in rats for a long period. Thus, the selection of carrier is an important factor in the development of solid SNEDDS, since the carriers had significant effects on the crystalline properties, dissolution and oral bioavailability of flurbiprofen and on the formation of solid SNEDDS.     

Development and optimisation of atorvastatin calcium loaded self-nanoemulsifying drug delivery system (SNEDDS) for enhancing oral bioavailability: in vitro and in vivo evaluation

The objective of this study was to develop and optimise self-nanoemulsifying drug delivery system (SNEDDS) of atorvastatin calcium (ATC) for improving dissolution rate and eventually oral bioavailability. Ternary phase diagrams were constructed on basis of solubility and emulsification studies. The composition of ATC–SNEDDS was optimised using the Box–Behnken optimisation design. Optimised ATC–SNEDDS was characterised for various physicochemical properties. Pharmacokinetic, pharmacodynamic and histological findings were performed in rats. Optimised ATC–SNEDDS resulted in droplets size of 5.66?nm, zeta potential of ?19.52?mV, t₉₀ of 5.43?min and completely released ATC within 30?min irrespective of pH of the medium. Area under the curve of optimised ATC–SNEDDS in rats was 2.34-folds higher than ATC suspension. Pharmacodynamic studies revealed significant reduction in serum lipids of rats with fatty liver. Photomicrographs showed improvement in hepatocytes structure. In this study, we confirmed that ATC–SNEDDS would be a promising approach for improving oral bioavailability of ATC.     

Statistical modeling,optimization and characterization of solid self-nanoemulsifying drug delivery system of lopinavir using design of experiment

Objective: Lopinavir (LPV), an antiretroviral protease inhibitor shows poor bioavailability because of poor aqueous solubility and extensive hepatic first-pass metabolism. The aim of the present work was to investigate the potential of the solid self-nanoemulsifying drug delivery system (S-SNEDDS) in improving dissolution rate and oral bioavailability of LPV.

Materials and methods: Liquid SNEDDS (L-SNEDDS) of LPV were prepared using Capmul MCM C8, Cremophor RH 40 and propylene glycol and their amounts were optimized by Scheffe’s mixture design. L-SNEDDS formulations were evaluated for different physicochemical and in vitro drug release parameters. S-SNEDDS were prepared by adsorbing L-SNEDDS on Neusilin US2 and characterized for solid-state properties. In vivo bioavailability of S-SNEDDS, marketed Lopinavir?+?Ritonavir (LPV/RTV) formulation and pure LPV was studied in Wistar rats. Stability study of S-SNEDDS was performed as per ICH guidelines.

Results and discussion: Optimized L-SNEDDS obtained by Scheffe design had drug loading 160?±?1.15?mg, globule size 32.9?±?1.45?nm and drug release?>95% within 15?min. Solid state studies suggested the transformation of the crystalline drug to amorphous drug. The size and zeta potential of globules obtained on dilution S-SNEDDS remained similar to L-SNEEDS. In vivo bioavailability study revealed that S-SNEDDS has 2.97 and 1.54-folds higher bioavailability than pure LPV and LPV/RTV formulation, respectively. The optimized S-SNEDDS was found to be stable and had a shelf life of 2.85 years.

Conclusion: The significant increase in drug dissolution and bioavailability by prepared SNEDDS suggest that the developed S-SNEDDS is a useful solid platform for improving oral bioavailability of poorly soluble LPV.     

Trans-resveratrol self-nano-emulsifying drug delivery system (SNEDDS) with enhanced bioavailability potential: optimization,pharmacokinetics and in situ single pass intestinal perfusion (SPIP) studies

Abstract

Trans-resveratrol (t-RVT) is a potent antioxidant. By virtue of extensive pre-systemic metabolism and existence of enterohepatic recirculation, t-RVT bioavailability is almost zero. The current study aimed to develop self-nanoemulsifying drug delivery systems (SNEDDS) using long-chain triglycerides (LCTs) of t-RVT in an attempt to circumvent such obstacles. Equilibrium solubility studies indicated the choice of Lauroglycol FCC as lipid, and of Labrasol and Transcutol P as surfactants, for formulating the SNEDDS. Ternary phase diagrams were constructed to select the areas of nanoemulsions, and the amounts of lipid (X₁) and surfactant (X₂) as the critical factor variables. The SNEDDS were optimized using 3² central composite design (CCD) and the optimized formulation (OPT) located using overlay plot. The nanometer size range and high negative values of zeta potential depicted non-coalescent nature of the SNEDDS. Optimized formulation indicated marked improvement in drug release profile vis-à-vis pure drug. Cloud point determination and accelerated stability studies ascertained the stability of OPT. Augmentation in the values of K_a (3.29-fold) and AUC (4.31-fold) indicated significant enhancement in the rate and extent of bioavailability by the OPT compared with pure drug. In situ perfusion (SPIP) studies in Wistar rats construed remarkable enhancement in the absorptivity and permeability parameters of SNEDDS vis-à-vis the pure drug. Successful establishment of level A of in vitro/in vivo correlation substantiated the judicious choice of the in vitro dissolution milieu for simulating the in vivo conditions. The present study, therefore, reports the successful development of SNEDDS with distinctly enhanced bioavailability of t-RVT.     

Solid self-nanoemulsifying drug delivery system (S-SNEDDS) for oral delivery of glimepiride: development and antidiabetic activity in albino rabbits

Abstract

Context: This study presents novel self-nanoemulsifying drug delivery system potential of oral delivering which leads poorly aqueous soluble drug glimepiride.

Objective: The objective of this study was to prepare solid self-nanoemulsifying drug delivery system (S-SNEDDS) for the improved oral delivery of glimepiride and to evaluate its therapeutic efficacy in albino rabbits.

Results and discussion: The droplet size analyses revealed a droplet size of less than 200?nm. The solid state characterization of S-SNEDDS by scanning electron microscopy (SEM), X-ray powder diffraction and differential scanning calorimetry (DSC) revealed the absence of crystalline glimepiride in the S-SNEDDS. The in vitro dissolution studies revealed that the significant improvement in glimepiride release characteristics. The effect of S-SNEDDS on therapeutic efficacy of glimepride was assessed in albino rabbits by monitoring blood glucose levels and compared with free drug suspension, L-SNEDDS. The S-SNEDDS showed significant (p?<?0.05) increase in in vitro drug release and therapeutic efficacy as compared with free drug.

Conclusion: This study demonstrated that S-SNEDDS is a promising novel drug delivery system of glimepride to enhance oral delivery.     

Solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing phosphatidylcholine for enhanced bioavailability of highly lipophilic bioactive carotenoid lutein

The objectives of this study was to prepare solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing phosphatidylcholine (PC), an endogenous phospholipid with excellent in vivo solubilization capacity, as oil phase for the delivery of bioactive carotenoid lutein, by spray drying the SNEDDS (liquid system) containing PC using colloidal silica (Aerosil® 200 VV Pharma) as the inert solid carrier, and to evaluate the enhanced bioavailability (BA) of lutein from S-SNEDDS. The droplet size analyses revealed droplet size of less than 100 nm. The solid state characterization of S-SNEDDS by SEM, DSC, and XRPD revealed the absence of crystalline lutein in the S-SNEDDS. The bioavailability study performed in rabbits resulted in enhanced values of C_max and AUC for S-SNEDDS. The enhancement of C_max for S-SNEDDS was about 21-folds and 8-folds compared with lutein powder (LP) and commercial product (CP), respectively. The relative BA of S-SNEDDS compared with CP or LP was 2.74-folds or 11.79-folds, respectively. These results demonstrated excellent ability of S-SNEDDS containing PC as oil phase to enhance the BA of lutein in rabbits. Thus, S-SNEDDS containing PC as oil phase could be a useful lipid drug delivery system for enhancing the BA of lutein in vivo.     

Physicochemical characterization and in vivo evaluation of solid self-nanoemulsifying drug delivery system for oral administration of docetaxel

To formulate a self-nanoemulsifying drug delivery system (SNEDDS) for the oral administration of docetaxel as an alternative to commercial docetaxel-loaded injectable products, it was prepared by spray-drying an aqueous solution containing liquid SNEDDS and colloidal silica. Its physicochemical properties and oral bioavailability were investigated compared to a clear docetaxel solution administered intravenously or orally to rats. In the docetaxel-loaded solid SNEDDS prepared with colloidal silica, the liquid SNEDDS composed of Capryol 90, Cremophore EL and Transcutol HP (45/35/20, volume ratio) was absorbed inside the pores of carriers, and docetaxel was present in a changed amorphous state. The solid SNEDDS with 3.3% (w/v) docetaxel produced nanoemulsions, and showed about 12.5% absolute bioavailability in rats. Thus, this solid SNEDDS may be a potential candidate for oral pharmaceutical product with improved oral bioavailability of docetaxel.     

Surface-adsorbed reverse micelle-loaded solid self-nanoemulsifying drug delivery system of talinolol

The aim of present investigation was to develop surface-adsorbed reverse-micelle-loaded solid self-nanoemulsifying drug delivery system (SNEDDS) of talinolol in order to enhance its in vitro dissolution rate, which in turn enhance the bioavailability. SNEDDS were prepared using aqueous phase titration method. Thermodynamically stable formulations were characterized in terms of droplet size, viscosity, % transmittance, drug content and surface morphology. Low cost acid-treated coffee husk was used as an effective biosorbent for preparation of solid SNEDDS. Developed SNEDDS were subjected to in vitro drug release/dissolution studies. In vitro drug release studies showed 99.6% release of talinolol from optimized solid SNEDDS TS3 after 120?min of study. The results of solubility studies showed 4849.5-folds enhancement in solubility of talinolol from optimized SNEDDS as compared to its aqueous solubility.     

Optimized self-nanoemulsifying drug delivery system of atazanavir with enhanced oral bioavailability: in vitro/in vivo characterization

Background: Atazanavir (ATV) is a HIV protease inhibitor. Due to its intense lipophilicity, the oral delivery of ATV encounters several problems such as poor aqueous solubility, pH-dependent dissolution and rapid first-pass metabolism in liver by CYP3A5, which result in low and erratic bioavailability.

Objective: The current study aimed to develop self-nanoemulsifying drug delivery systems (SNEDDS) using long-chain triglycerides of ATV in an attempt to circumvent such obstacles.

Methods: Equilibrium solubility studies indicated the choice of Maisine 35-1 as lipid, and of Transcutol P and Span 20 as surfactants, for formulating the SNEDDS. Ternary phase diagrams were constructed to select the areas of nanoemulsions, and the amounts of lipid (X₁) and surfactant (X₂) as the critical factor variables. The SNEDDS were optimized (OPT) using 3² central composite design and the OPT formulation located using overlay plot. The pharmacokinetics and in situ single-pass intestinal perfusion studies of OPT formulation were investigated in Wistar rats.

Results: OPT formulation indicated marked improvement in drug release profile vis-à-vis pure drug. Cloud point determination and accelerated stability studies ascertained the stability of OPT formulation. Augmentation in the values of K_a (1.96-fold) and AUC (2.57-fold) indicated significant enhancement in the rate and extent of bioavailability by the OPT formulation compared to pure drug. Successful establishment of in vitro/in vivo correlation Level A substantiated the judicious choice of the in vitro dissolution milieu for simulating the in vivo conditions.

Conclusion: The studies, therefore, indicate the successful formulation development of SNEDDS with distinctly improved bioavailability of ATV.     

From nanoemulsions to self-nanoemulsions,with recent advances in self-nanoemulsifying drug delivery systems (SNEDDS)

Introduction: Lipid-based drug delivery systems (LBDDS) are the most promising technique to formulate the poorly water soluble drugs. Nanotechnology strongly influences the therapeutic performance of hydrophobic drugs and has become an essential approach in drug delivery research. Self-nanoemulsifying drug delivery systems (SNEDDS) are a vital strategy that combines benefits of LBDDS and nanotechnology. SNEDDS are now preferred to improve the formulation of drugs with poor aqueous solubility.

Areas covered: The review in its first part shortly describes the LBDDS, nanoemulsions and clarifies the ambiguity between nanoemulsions and microemulsions. In the second part, the review discusses SNEDDS and elaborates on the current developments and modifications in this area without discussing their associated preparation techniques and excipient properties.

Expert opinion: SNEDDS have exhibit the potential to increase the bioavailability of poorly water soluble drugs. The stability of SNEDDS is further increased by solidification. Controlled release and supersaturation can be achieved, and are associated with increased patient compliance and improved drug loads, respectively. Presence of biodegradable ingredients and ease of large-scale manufacturing combined with a lot of ‘drug-targeting opportunities’ give SNEDDS a clear distinction and prominence over other solubility enhancement techniques.     

Zero-order release and bioavailability enhancement of poorly water soluble Vinpocetine from self-nanoemulsifying osmotic pump tablet

Abstract

Solid self-nanoemulsifying (S-SNEDDS) asymmetrically coated osmotic tablets of the poorly water-soluble drug Vinpocetine (VNP) were designed. The aim was to control the release of VNP by the osmotic technology taking advantage of the solubility and bioavailability-enhancing capacity of S-SNEDDS. Liquid SNEDDS loaded with 2.5?mg VNP composed of Maisine? 35-1, Transcutol^® HP, and Cremophor^® EL was adsorbed on the solid carrier Aeroperl^®. S-SNEDDS was mixed with the osmotic tablet excipients (sodium chloride, Avicel^®, HPMC-K4M, PVP-K30, and Lubripharm^®), then directly compressed to form the core tablet. The tablets were dip coated and mechanically drilled. A 3²*2¹ full factorial design was adopted. The independent variables were: type of coating material (X₁), concentration of coating solution (X₂), and number of drills (X₃). The dependent variables included % release at 2?h (Y₁), at 4?h (Y₂), and at 8?h (Y₃). The in vivo performance of the optimum formula was assessed in rabbits. Zero-order VNP release was obtained by the single drilled 1.5% Opadry^® CA coated osmotic tablets and twofold increase in VNP bioavailability was achieved. The combination of SNEDDS and osmotic pump tablet system was successful in enhancing the solubility and absorption of VNP as well as controlling its release.     

Cell-penetrating self-nanoemulsifying drug delivery systems (SNEDDS) for oral gene delivery

ABSTRACT

Objective: The aim of study was to investigate whether cell-penetrating peptides could amplify cellular uptake of plasmid DNA (pDNA) loaded self-nanoemulsifying drug delivery systems (SNEDDS) by mucosal epithelial cells, thereby enhancing transfection efficiency.

Methods: HIV-1 Tat peptide-oleoyl conjugate (TAT-OL) was synthesized through amide bond formation between HIV-1 Tat-protein 49–57 (TAT) and oleoyl-chloride (OL). SNEDDS formulation contained 29.7% each of Cremophor EL, Capmul MCM and Crodamol, 9.9% propylene glycol and 1% TAT-OL. SNEDDS with OL instead of TAT-OL served as control.

Results: Fluorescent-microscopy demonstrated 0.5% (m/v) nanoemulsions were suitable for subsequent studies. Mucus diffusion of nanoemulsion loaded with fluorescein diacetate (FDA) was 1.5-fold increased by incorporation of TAT-OL. Confocal microscopy confirmed that droplets of nanoemulsions were successfully internalized. Furthermore, quantitative analysis showed that addition of TAT-OL increases uptake of nanoemulsions by 2.3- and 2.6-folds after 2 and 4 hours of incubation, respectively. Cellular internalization pathways were found with substantial decrease in uptake in presence of indomethacin and chlorpromazine. Transfection efficiency investigated on HEK-293-cells was found to be 1.7- and 1.8-fold higher for SNEDDS loaded with TAT-OL compared to Lipofectin and control, respectively.

Conclusion: In comparison to prevailing lipid and polymer-based delivery systems, these novel cell-penetrating SNEDDS likely represent most effective, simplistic and expedite dosage form for mucosal gene delivery.     

Development of a biocompatible creatinine-based niosomal delivery system for enhanced oral bioavailability of clarithromycin

Context: Nonionic surfactant vesicles have gained increasing scientific attention for hydrophobic drugs delivery due to their biocompatibility, stability and low cost.

Objective: The aim of the present study was to synthesize and evaluate a novel creatinine-based nonionic surfactant in terms of its ability to generate biocompatible niosomal system for the delivery of Clarithromycin.

Materials and Methods: The surfactant was synthesized by reacting creatinine with lauroyl chloride followed by characterization using ¹HNMR and MS. The drug-loaded niosomal vesicles of the surfactant were characterized for drug encapsulation efficiency (EE) using LC-MS, vesicle size using dynamic light scattering (DLS) and vesicle shape using atomic force microscopy (AFM). The surfactant was also investigated for blood hemolysis, in vitro cytotoxicity against different cell lines and in vivo acute toxicity in mice. Furthermore, the in vivo bioavailability of Clarithromycin encapsulated in the novel niosomal formulation was investigated using rabbits and quantified through validated LC-MS/MS method.

Results and discussion: Findings showed that vesicles were able to entrap up to 67.82?±?1.27% of the drug, and were rounded in shape with a size around 202.73?±?5.30?nm and low polydispersity. The surfactant caused negligible blood hemolysis, very low cytotoxicity and was found to be safe up to 2500?mg/kg body weight using mice. The niosomal formulation showed twofold enhanced oral bioavailability of Clarithromycin as compared to commercial formulations of the drug.

Conclusion: The study has shown that the creatinine-based niosomes developed in our laboratory were biocompatible, safe and increased the oral bioavailability of the model hydrophobic Clarithromycin using experimental animals.     

A comprehensive study of the basic formulation of supersaturated self-nanoemulsifying drug delivery systems (SNEDDS) of albendazolum

Albendazolum (ABZ) is a BCS class II drug. It has challenging biopharmaceutical properties, which include poor solubility and dissolution rate. These properties have laid the ground for developing a supersaturated self-nanoemulsifying drug delivery system (S-SNEDDS) to form oil-in-water nanoemulsion in situ to improve the oral bioavailability of ABZ. Based on the ABZ solubility, emulsifying ability, and stability after dispersion in an aqueous phase, an optimal self-nanoemulsifying drug delivery system (SNEDDS) consisting of oleic acid, Tween^® 20, and PEG 600 (X:Y:Z, w/w) was identified, having 10% (w/w) hydroxypropyl methylcellulose (HPMC) E15 lv as its precipitation inhibitor. The optimized system possessed a small mean globule size value (89.2 nm), good dispersion properties (polydispersity index (PDI): 0.278), and preserved the supersaturated state of ABZ. S-SNEDDS was transformed into solid supersaturated self-nanoemulsifying drug delivery systems (SS-SNEDDS) using microcrystalline cellulose as a solid material. The developed S-SNEDDS were characterized for globule size, pH, turbidity, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and flow properties. The data obtained from the results suggest that this S-SNEDDS formulation can enhance the solubility and oral bioavailability of ABZ for appropriate clinical application.     

Oral self-nanoemulsifying peptide drug delivery systems: impact of lipase on drug release

Abstract

It was the aim of this study to evaluate the impact of lipases on the release behaviour of a peptide drug from oral self-nanoemulsifying drug delivery systems. Octreotide was ion paired with the anionic surfactants deoxycholate, decanoate, oleate and dodecylsulphate. The lipophilic character of these complexes was characterised by determining the n-octanol/buffer pH 7.4 partition coefficient. In the following the most hydrophilic complex was incorporated in a likely lipase degradable self-nanoemulsifying drug delivery systems (SNEDDS) formulation containing a triglyceride (olive oil; Pharm.Eur.) and in a likely not lipase degradable SNEDDS containing lipids and surfactants without any ester bonds. After 1:100 dilutions in artificial intestinal fluid (AIF), the lipid droplets were characterised regarding size distribution. With these SNEDDS, drug release studies were performed in AIF with and without lipase. Results showed that the most hydrophobic complex can be formed with deoxycholate in an octreotide:anionic surfactant ratio of 1:5. Even 73.1?±?8.1% of it could be quantified in the n-octanol phase. SNEDDS containing octreotide | olive oil | cremophor EL | propylene glycol (2|57|38|3) and octreotide | liquid paraffin | Brij 35 | propylene glycol | ethanol (2|66.5|25|5|1.5) showed after dilution in AIF, a mean droplet size of 232?±?53?nm and 235?±?50?nm, respectively. Drug release studies showed a sustained release of octreotide out of these formulations for at least 24?h, whereas?>?80% of the drug was released within 2?h in the presence of lipase in the case of the triglyceride containing SNEEDS. In contrast the release profile from ester-free SNEDDS was not significantly altered (p?<?0.05) due to the addition of lipase providing evidence for the stability of this formulation towards lipases. According to these results, SNEDDS could be identified as a useful tool for sustained oral peptide delivery taking an enzymatic degradation by intestinal lipases into considerations.     

QbD-based systematic development of novel optimized solid self-nanoemulsifying drug delivery systems (SNEDDS) of lovastatin with enhanced biopharmaceutical performance

Abstract

Of late, solid self-nanoemulsifying drug delivery systems (S-SNEDDS) have been extensively sought-after owing to their superior portability, drug loading, stability and patient compliance. The current studies, therefore, entail systematic development, optimization and evaluation (in vitro, in situ and in vivo) of the solid formulations of (SNEDDS) lovastatin employing rational quality by design (QbD)-based approach of formulation by design (FbD). The patient-centric quality target product profile (QTPP) and critical quality attributes (CQAs) were earmarked. Preformulation studies along with initial risk assessment facilitated the selection of lipid (i.e. Capmul MCM), surfactant (i.e. Nikkol HCO-50) and co-surfactant (i.e. Lutrol F127) as CMAs for formulation of S-SNEDDS. A face-centered cubic design (FCCD) was employed for optimization using Nikkol-HCO50 (X₁) and Lutrol-F127 (X₂), evaluating CQAs like globule size, liquefaction time, emulsification time, MDT, dissolution efficiency and permeation parameter. The design space was generated using apt mathematical models, and the optimum formulation was located, followed by validation of the FbD methodology. In situ SPIP and in vivo pharmacodynamic studies on the optimized formulation carried out in unisex Wistar rats, corroborated superior drug absorption and enhanced pharmacodynamic potential in regulating serum lipid levels. In a nutshell, the present studies report successful QbD-oriented development of novel oral S-SNEDDS of lovastatin with distinctly improved biopharmaceutical performance.     

Preparation,in vitro and in vivo evaluation of solid-state self-nanoemulsifying drug delivery system (SNEDDS) of vitamin A acetate

Vitamin A self-nanoemulsifying drug delivery system (SNEDDS), which comprises soybean oil, Cremophor EL, and Capmul MCM-C8, was prepared and mixed with different grades of Avicel to produce homogenized powders. The resultant powders were compressed into tablets. The prepared tablets were characterized for their thickness, hardness, friability, disintegration time, and dissolution rate. In addition, the relative bioavailability of the tablets in comparison to solid-state Vitamin A oily solution (SSVAOS) tablets was investigated in rats. Vitamin A dissolution rate was markedly different from one formulation to another. From the bioavailability data, it was observed that Vitamin A SNEDD tablets have higher bioavailability (relative bioavailability 143.68%) compared with SSVAOS tablets. The AUC and C_max of Vitamin A SNEDD tablets were found to be significantly different from that of SSVAOS tablets.     

Self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble grapefruit flavonoid Naringenin: design,characterization, in vitro and in vivo evaluation

Abstract

Naringenin (NRG), predominant flavanone in grapefruits, possesses anti-inflammatory, anti-carcinogenic, hepato-protective and anti-lipid peroxidation effects. Slow dissolution after oral ingestion due to its poor solubility in water, as well as low bioavailability following oral administration, restricts its therapeutic application. The study is an attempt to improve the solubility and bioavailability of NRG by employing self-nanoemulsifying drug delivery technique. Preliminary screening was carried out to select oil, surfactant and co-surfactant, based on solubilization and emulsification efficiency of the components. Pseudo ternary phase diagrams were constructed to identify the area of nanoemulsification. The developed self-nanoemulsifying drug delivery systems (SNEDDS) were evaluated in term of goluble size, globule size distribution, zeta potential, and surface morphology of nanoemulsions so obtained. The TEM analysis proves that nanoemulsion shows a droplet size less than 50?nm. Freeze thaw cycling and centrifugation studies were carried out to confirm the stability of the developed SNEDDS. In vitro drug release from SNEDDS was significantly higher (p?<?0.005) than pure drug. Furthermore, area under the drug concentration time-curve (AUC_0–24) of NRG from SNEDDS formulation revealed a significant increase (p?<?0.005) in NRG absorption compared to NRG alone. The increase in drug release and bioavailability as compared to drug suspension from SNEDDS formulation may be attributed to the nanosized droplets and enhanced solubility of NRG in the SNEDDS.     

Facile synthesis of PEI-based crystalline templated mesoporous silica with molecular chirality for improved oral delivery of the poorly water-soluble drug

The aim of this study was to build up a novel chiral mesoporous silica called PEIs@TA-CMS through a facile biomimetic strategy and to explore its potential to serve as a drug carrier for improving the delivery efficiency of poorly water-soluble drug. PEIs@TA-CMS was synthesized by using a chiral crystalline complex associated of tartaric acid and polyethyleneimine (PEIs) as templates, scaffolds and catalysts. The structural features including morphology, size, pore structure and texture properties were systematacially studied. The results showed that PEIs@TA-CMS was monodispersed spherical nanoparticles in a uniformed diameter of 120–130 nm with well-developed pore structure (S_BET: 1009.94 m²/g, pore size <2.21 nm). Then PEIs@TA-CMS was employed as nimodipine (NMP) carrier and compared with the drug carry ability of MCM41. After drug loading, NMP was effectively transformed from the crystalline state to an amorphous state due to the space confinement in mesopores. As expected, PEIs@TA-CMS had superiority in both drug loading and drug release compared to MCM41. It could incorporate NMP with high efficiency, and the dissolution-promoting effect of PEIs@TA-CMS was more obvious because of the unique interconnected curved pore channels. Meanwhile, PEIs@TA-CMS could significantly improve the oral adsorption of NMP to a satisfactory level, which showed approximately 3.26-fold higher in bioavailability, and could effectively prolong the survival time of mice on cerebral anoxia from 10.98 to 17.33 min.