Solid Self-nanoemulsifying Drug Delivery System Research Articles

Pharmacokinetic and pharmacodynamic evaluation of Solid self-nanoemulsifying delivery system (SSNEDDS) loaded with curcumin and duloxetine in attenuation of neuropathic pain in rats.

The present investigation is focused on improving oral bioavailability of poorly soluble and lipophilic drugs, curcumin (CRM) and duloxetine (DXH), through the solid self-nanoemulsifying drug delivery system (S-SNEDDS) and identifying their potential against attenuation of NP in chronic constriction injury (CCI)-induced rats through the solid self-nanoemulsifying drug delivery system (S-SNEDDS). The optimized batch of S-SNEDDS reported was containing CRM and DXH (30 mg each), castor oil (20% w/w), tween-80 (40% w/w), transcutol-P (40% w/w), and syloid 244 FP (1 g). The high dose of each of naïve CRM (NCH), naïve DXH (NDH), physical mixture of DXH and CRM (C-NCM-DXH), S-SNEDDS-CRM (SCH), S-SNEDDS-DXH (SDH), and S-SNEDDS-CRM-DXH (C-SCH-SDH) was subjected for MTT assay. The developed formulations were subjected to pharmacokinetic studies and results showed about 8 to 11.06 and 2-fold improvement in oral bioavailability of CRM and DXH through S-SNEDDS. Furthermore, CCI-induced male Wistar rats were treated with SSNEDDS containing CRM and DXH, S-SNEDDS containing individual drug, individual naïve forms, and their combination from the day of surgery for 14 days and evaluated for behavioral at pre-determined time intervals. On the terminal day, animals were sacrificed to assess tissue myeloperoxidase, superoxide anion, protein, tumor necrosis factor-α, total calcium levels, and histopathological changes. Pronounced effect was observed in rats treated with S-SNEDDS containing both drugs with respect to rats receiving any of other treatments owing to enhanced oral bioavailability through S-SNEDDS. Therefore, it can be concluded that S-SNEDDS of both drugs and their coadministration can accelerate the prevention of NP.

Exploring role of probiotics and Ganoderma lucidum extract powder as solid carriers to solidify liquid self-nanoemulsifying delivery systems loaded with curcumin

Solid self-nanoemulsifying drug delivery system (S-SENDDS) containing Curcumin (CRM) were prepared using combination of Ganoderma lucidum extract powder (GLEP) and probiotics (PB) as carriers. Liquid SNEDDS containing CRM were prepared by mixing Capmul MCM, Labrafil M1944CS, Tween 80 and Transcutol P. These were further spray dried and finally converted into spheroids. The droplet size of reconstituted S-SNEDDS powder and spheroids was found in the range of 35 to 37 nm, zeta potential in the range of - 21.48 to -23.22 mV and drug loading in the range of 95-96%. The release of drug from formulations was found to be more than 90%. Similarly, significant improvement (p < 0.05) in permeability of CRM was observed through SNEDDS using Caco2 cell lines. The non-significant difference (p> 0.05) in drug loading, droplet size, dissolution rate and angle of repose between L-SNEDDS and S-SNEDDS indicated the potential of GLEP-PB to produce stable SNEDDS.

A Solid Ultra Fine Self-Nanoemulsifying Drug Delivery System (S-SNEDDS) of Deferasirox for Improved Solubility: Optimization, Characterization, and In Vitro Cytotoxicity Studies

The research work was designed to develop a solid self-nanoemulsifying drug delivery system (S-SNEDDS) of deferasirox (DFX). According to the solubility studies of DFX in different components, Peceol, Kolliphor EL, and Transcutol were selected as excipients. Pseudo-ternary phase diagrams were constructed, and then SNEDDS formation assessment studies and solubility of DFX in selected SNEDDSs formulations were performed. DFX loaded SNEDDS were prepared and characterized. The optimum DFX-SNEDDS formulations were developed. The relative safety of the optimized SNEDDS formulation was examined in a human immortalized myelogenous leukemia cell line, K562 cells, using the MTT cell viability test. Cytotoxicity studies revealed more cell viability (71.44%) of DFX loaded SNEDDS compared to pure DFX (3.99%) at 40 μM. The selected DFX-SNEDDS formulation was converted into S-SNEDDS by adsorbing into porous carriers, in order to study its dissolution behavior. The in vitro drug release studies indicated that DFX release (Q5%) from S-SNEDDS solidified with Neusilin UFL2 was significantly higher (93.6 ± 0.7% within 5 min) compared with the marketed product (81.65 ± 2.10%). The overall results indicated that the S-SNEDDS formulation of DFX could have the potential to enhance the solubility of DFX, which would in turn have the potential to improve its oral bioavailability as a safe novel delivery system.

Integrated Quality by Design Approach for Developing Nanolipidic Drug Delivery Systems of Olmesartan Medoxomil with Enhanced Antihypertensive Action.

Purpose: The present work endeavors to report a systematic approach of developing the lipidic self-nanoemulsifying formulation of olmesartan medoxomil (OMT) on the principles of Quality by Design (QbD). Methods: For preparing the self-nanoemulsifying formulation, a mixture of oil, surfactant and cosurfactant were used as vehicles. The excipients were selected after screening by solubility as well as pseudoternary phase titration studies. Mixture design was adopted for systematic optimization of the composition of nanolipidic formulations, which were evaluated for smaller globule size, stable zeta potential and lower values of polydispersity index. The optimized liquid self-nanoemulsifying formulation was identified using numerical and graphical optimization techniques, followed by validation of the experimental model. Solidification of self-nanoemulsifying formulation was carried out using porous carriers, and then optimized on the basis of oil adsorption potential, powder flow property and drug release performance. Pharmacokinetic study was performed in male Wistar rats for evaluating the drug absorption parameters. All the experimental data obtained were subjected to statistical analysis using oneway ANOVA followed by post hoc analysis using Student’s t test. Results: The optimized liquid self-nanoemulsifying formulation showed globule size <100 nm, emulsification efficiency <5 minutes andin vitro drug release >85% within in 30 minutes. Further, the solid SNEDDS formulation was effectively formulated using Neusilin US2 with maximum oil adsorption capacity and good micromeritic properties. Pharmacokinetic evaluation indicated 4 to 5-folds increase (P <0.05) in the values of Cmax, AUC, and reduction in Tmax from the nanoformulations vis-à-vis the marketed formulation. Conclusion: Overall, the developed nanolipidic formulation of olmesartan indicated superior efficacy in augmenting the drug dissolution and absorption performance.

Development and evaluation of rhubarb free anthraquinones loaded self-nanoemulsifying tablets

The paper aims to design and prepare rhubarb free anthraquinones (RhA) loaded solid self-nanoemulsifying drug delivery system (S-SNEDDS) to improve RhA's solubility and physical stability of RhA loaded nano emulsion. Suitable adsorbents of pre-concentrated RhA loaded nano emulsion were selected based on saturated adsorption capacity, flowability and reconsitution properties. The possible interactions among RhA, adsorbents and other excipients were investigated using powder X-ray diffraction and FTIR spectroscopy. RhA loaded SNEDDS tablets were designed and optimized using central composite design. In vitro dissolution, pharmacokinetics and stress stability were comparatively conducted to validate the advantages of RhA loaded SNEDDS tablets. No chemical interactions existed between the main materials. The optimal RhA loaded SNEDDS tablet formulation consisted of 1:1(w/w) Neusilin US2/pre-concentrated RhA loaded nanoemulsion, 5.0% (w/w) PVPP, 1% (w/w) Mg stearate. More than 90% RhA released from RhA loaded SNEDDS tablets while less than 10% were released from control tablets within 360 min. RhA in the SNEDDS tablets showed much improved absorption in comparison to control tablets. The percentage contents of RhA in the SNEDDS tablets were decreased more slowly than in RhA loaded nanoemlusion under stress conditions. The current study suggests that RhA loaded SNEDDS tablets could be an effective approach to improve RhA's solubility, bioavailability and physical stability of RhA loaded nanoemulsion.

Bioactive Self-Nanoemulsifying Drug Delivery Systems (Bio-SNEDDS) for Combined Oral Delivery of Curcumin and Piperine.

Background: Bioactive oils of natural origin have gained huge interests from health care professionals and patients. Objective: To design a bioactive self-nanoemulsifying drug delivery system (Bio-SNEDDS) comprising curcumin (CUR) and piperine (PP) by incorporating bioactive natural oils in the formulation. Methods: The self-emulsifying properties of apricot, avocado, black seed and Zanthoxylum rhetsa seed oils were screened within various SNEDDS formulations. Each liquid SNEDDS formulation was loaded with both CUR and PP. The optimal liquid SNEDDS were solidified using Aeroperl® and Neusilin® at 1:1 w/w ratio. Liquid and solid SNEDDS were characterized by droplet size analysis, equilibrium solubility, scanning electron microscopy, X-ray powder diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy. In-vitro dissolution studies were performed to evaluate the efficiency of CUR and PP release from solid Bio-SNEDDS. Results: The liquid SNEDDS comprised of black seed oil exhibited excellent self-emulsification performance, low droplet size along with transparent appearance. The inclusion of the cosolvent Transcutol P improved the solubilization capacity of both CUR and PP. The liquid SNEDDS were efficiently solidified using the two adsorbents and presented the drugs within amorphous state. In particular, SNEDDS comprised of black seed oil/Imwitor988/Transcutol P/Cremophor RH40 (20/20/10/50) and when solidified with Neusilin showed enhanced CUR and PP release (up to 60% and 77%, respectively). In addition, this formulation efficiently delivers the highly bioactive black seed oil to the patient. Conclusions: The optimized Bio-SNEDDS comprising black seed oil showed outstanding self-emulsification characteristics along with enhanced CUR/PP dissolution upon solidification.

Impact of solidification on micromeritic properties and dissolution rate of self-nanoemulsifying delivery system loaded with docosahexaenoic acid

Development of self-nanoemulsifying drug delivery systems (SNEDDS) of docosahexaenoic acid (DHA) is reported with the aim to achieve enhanced dissolution rate. The optimized composition of liquid SNEDDS (L-SNEDDS) formulation was Labrafil M1944 CS, 47% v/v Tween 80, 27% v/v Transcutol P, and 0.1% v/v DHA. L-SNEDDS were solidified using Syloid XDP 3150 as solid porous carrier. The droplet size, polydispersity index, zeta potential, percentage drug loading, and cloud point for L-SNEDDS were found to be 43.51 ± 1.36 nm, 0.186 ± 0.053, −19.20 ± 1.21 mV, 93.23 ± 1.71, and 88.60 ± 2.54 °C, respectively. Similarly, for solid SNEDDS (S-SNEDDS) the above parameters were found to be 57.32 ± 1.87 nm, 0.261 ± 0.043, −16.60 ± 2.18 mV, 91.23 ± 1.88, and 89.50 ± 1.18 °C, respectively. The formulations (L-SNEDDS, S-SNEDDS powder, and S-SNEDDS tablet) showed significant (p<.05) improvement in dissolution rate of drug in 0.1 N HCl (pH 1.2) and phosphate buffer (pH 6.8) as compared to unprocessed DHA. In both the dissolution media, the dissolution rate was found more that 85% in 90 min. Absence of drug precipitation, phase separation, and turbidity during thermodynamic stability studies indicated that the developed SNEDDS were stable. Hence, it was concluded that SNEDDS have offered sufficient stability as well as dissolution rate of DHA.

Solid self-nanoemulsifying drug delivery system filled in enteric coated hard gelatin capsules for enhancing solubility and stability of omeprazole hydrochloride

Omeprazole has poor water solubility, low stability in acidic solutions, and is subject to first pass metabolism resulting in low bioavailability. The objective was to enhance the dissolution and stability by preparing a solid-self nanoemulsifying drug delivery system (SNEDDS) and filling it in enteric coated HGCs. Drug solubility in many oils, surfactants, and cosurfactants was studied. Different SNEDDS were prepared and ternary phase diagrams were constructed. The optimum SNEDDS was evaluated. It was converted into solid by adsorption onto Neusilin® US2, and evaluated. Emulsions formed using Capryol 90, Cremophor RH 40, and ethanol formed spontaneously and were clear. Droplet size was 19.11 ± 3.11 nm, PDI was 0.18 ± 0.05, and zeta potential was –3.9 ± 1.56 mV. Non-medicated SNEDDS was thermodynamically stable. Cloud point was 88 ± 2 °C. Encapsulation efficiency and drug loading of solid-SNEDDS were 98.56 ± 0.44 and 1.29 ± 0.01%, respectively. Flow properties were much enhanced. Crystalline drug was adsorbed/precipitated onto Neusilin® US2 in amorphous form. Dissolution rate was enhanced as compared to commercial products and unprocessed drug. The drug was unstable at the accelerated stability conditions. Accordingly, the traditional stability study at 25 °C should be conducted. In conclusion, the solid-SNEDDS filled in enteric coated HGCs enhanced the dissolution rate and stability in acidic pH.

Self-nanoemulsifying drug delivery systems (SNEDDS) for oral delivery of Garcinia kola seeds ethanolic extract: formulation and in vivo antimalarial activity

Context: Garcinia kola seeds are widely used in Congolese traditional medicine to treat uncomplicated malaria. While the ethanolic extract of these seeds (GK) is reputed for oral antimalarial activity, some of its constituents have shown poor water solubility, which might compromise further phytopharmaceutical developments. Aims: To develop a self-nanoemulsifying drug delivery system (SNEDDS) for oral delivery of GK, since SNEDDS are promising vehicles for enhancing drug product solubility. Methods: GK was loaded into liquid SNEDDS (solution and suspension) and solid SNEDDS (S-SNEDDS), and the resultant formulations were characterized using dynamic light scattering and electron microscopy. The antimalarial activity of SNEDDS (200 mg/kg × 4 days, oral) was evaluated in Plasmodium berghei-infected mice using a conventional four-day suppressive test. Results: The characterization of SNEDDS formulations revealed the presence of nanosized structures of spherical morphology and negative surface charge. Data from in vivo study showed reduced parasite growth by 77.9, 73.8 and 74.2% for GK-SNEDDS solution, GK-SNEDDS suspension and GK-S-SNEDDS, respectively. The activity of GK-SNEDDS was found to be greater than that of a licensed GK-based syrup (N’sansiphos®) used at the same dose (p&lt;0.05). Conclusions: These findings demonstrate the potential of SNEDDS formulations as a promising alternative for enhancing the antimalarial efficacy of GK following oral administration. The SNEDDS technology holds the promise of improving the oral delivery of herbal-based products for malaria therapy.

Enhancing oral absorption of poorly water-soluble herb (Kaempferia parviflora) extract using self-nanoemulsifying formulation

Kaempferia parviflora, a medicinal herb, treats hypertension and promotes longevity with good health and well-being. Its bioactive component is poorly soluble in water, resulting in poor absorption. This study aimed to enhance the bioavailability of K. parviflora dichloromethane (KPD) extract using a self-nanoemulsifying drug delivery system (SNEDDS). KPD was dissolved in diethylene glycol monoethyl, polyoxyl-35 castor oil and caprylic/capric glyceride, and clear yellow SNEDDS solution was obtained. The methoxyflavone markers were used for content and dissolution analysis. Solid SNEDDS was prepared by stepwise mixing of KPD using a mortar and pestle (1:1 ratio) with five solid carriers: Aerosil® 200, Florite® RE, Neusilin® US2 (NEUS), Fujicalin®, and Neusilin® UFL2. The USP apparatus II with simulated gastric fluid USP (SGF without pepsin, pH 1.2) was used in order to perform the in vitro dissolution. The methoxyflavones dissolution at 60 min from KPD, SEDDS, and SNEDDS/NEUS were approximately 16, 92, and 73%, respectively. The pharmacokinetic profiles of methoxyflavones for oral administration were studied using Wistar rats; the areas under the curve of SNEDDS/NEUS (1.77-fold) and SNEDDS (5.38-fold) were significantly higher than that of KPD. The developed formulations showed good stability after storage for 6 months under accelerated and normal conditions.

Formulation and Pharmacokinetic Evaluation of Phosal Based Zaltoprofen Solid Self-Nanoemulsifying Drug Delivery System.

:Background: Phosal based excipients are liquid concentrates containing phospholipids. They are used to solubilize water-insoluble drug and also act as an emulsifier to get the smallest droplet size of the formed emulsion after administration.Objective:The aim is to prepare phosal based self nanoemulsifying drug delivery system (SNEDDS) for water insoluble drug zaltoprofen.Methods: The various parameters like solubility of drug in different vehicles, ternary phase diagram are considered to formulate the stable emulsion which is further characterized by Self emulsification time and globule size analysis to optimize liquid SNEDDS of Zaltoprofen. Optimized L-SNEDDS was converted into free-flowing powder Solid-SNEDDS (S-SNEDDS). S-SNEDDS was evaluated for Globule size analysis after reconstitution, in vitro dissolution study and in vivo pharmacokinetic study in rats.Results: Phosal 53 MCT with highest drug solubility was used as oil along with Tween 80 and PEG 400 as surfactant and cosurfactant respectively to prepare liquid SNEDDS. Neusilin us2 was used as an adsorbent to get free-flowing S-SNEDDS. S-SNEDDS showed improved dissolution profile of the drug as compared to pure drug. In vivo study demonstrated that there is a significant increase in Cmax and AUC of S-SNEDDS compared to zaltoprofen powder.Conclusion:Phosal based SNEDDS formation can be successfully used to improve the dissolution and oral bioavailability of poorly soluble drug zaltoprofen.

Solidification of meloxicam self-nano emulsifying drug delivery system formulation incorporated into soluble and insoluble carriers using freeze drying method

Solidification of liquid self-nano emulsifying drug delivery system (SNEDDS) formulation is required to enhance the feasibility and flexibility for further formulation processes. This study purposed to compare the soluble and insoluble carriers namely mannitol and fumed silica, respectively on the nano-emulsion formation and physical properties. The optimized SNEDDS formulation comprising of virgin olive oil, Tween 80, and PEG 400; and meloxicam was impregnated into solid carriers e.g. mannitol and fumed silica using a freeze-drying method. The physical mixture was carried out to compare the aforementioned method. Vibrational spectroscopy, thermal analysis, and morphological characteristic, droplet size and distribution, and drug release were performed to characterize the solid SNEDDS (S-SNEDDS). The result showed that crystallization of meloxicam did not observe in the S-SNEDDS formulations, which confirmed by the vibrational spectroscopy and thermal analysis. The morphological characteristic of S-SNEDDS was similar to the native carriers. The soluble carrier did not affect the formation of the nano-emulsion compared to the insoluble carrier. In addition, the S-SNEDDS enhanced the drug release of meloxicam up to 3-4 folds increment.

Comparison of 1-Palmitoyl-2-Linoleoyl-3-Acetyl-Rac-Glycerol-Loaded Self-Emulsifying Granule and Solid Self-Nanoemulsifying Drug Delivery System: Powder Property, Dissolution and Oral Bioavailability.

The main objective of this study was to compare the powder property, dissolution and bioavailability of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG)-loaded self-emulsifying granule system (SEGS) and solid self-nanoemulsifying drug delivery system (SNEDDS). Various SEGS formulations were prepared, and the effect of surfactant and binder on the drug solubility in them, leading to selecting sodium lauryl sulphate (SLS) and hydroxyl propyl methyl cellulose (HPMC). The SEGS and SNEDDS were prepared with PLAG/SLS/HPMC/calcium silicate/microcrystalline cellulose at the weight ratio of 1:0.25:0.1:0.5:3 employing the fluid bed granulation and spray-drying technique, respectively. Their powder properties were compared in terms of flow ability, emulsion droplet size, scanning electron microscopy, and powder X-ray diffraction. Furthermore, the solubility, dissolution, and oral bioavailability in rats of the SEGS were assessed in comparison with the SNEDDS. The SEGS and SNEDDS enhanced the solubility of the drug approximately 36- and 32-fold as compared with the drug alone; but they had no differences. The crystalline drug may exist in both the calcium silicate and microcrystalline cellulose (MCC) in the SEGS, but only in the calcium silicate in the SNEDDS. The SEGS had considerably improved the flow ability (Hausner ratio, 1.23 vs. 1.07; Carr index, 19.8 vs. 43.5%) and drug dissolution as compared with the SNEDDS. The SEGS and SNEDDS with double peak profiles, unlike the single peak of drug alone, showed a significantly higher plasma concentration and area under the curve (AUC), as compared with drug alone. Although they were not significantly different, the SEGS gave higher AUC than did the SNEDDS, suggesting its enhanced oral bioavailability of PLAG. Thus, the SEGS could be used as a powerful oral dosage form to improve the flow ability and oral bioavailability of PLAG, an oily drug.

Quality by Design Approach for the Development of Self-Emulsifying Systems for Oral Delivery of Febuxostat: Pharmacokinetic and Pharmacodynamic Evaluation.

The goal of the present investigation is to formulate febuxostat (FXT) self-nanoemulsifying delivery systems (liquid SNEDDS, solid SNEDDS, and pellet) to ameliorate the solubility and bioavailability. To determine the self-nanoemulsifying region, ternary plot was constructed utilizing Capmul MCM C8 NF® as an oil phase, Labrasol® as principal surfactant, and Transcutol HP® being the co-surfactant. Liquid SNEDDS (L-SNEDDS) were characterized by evaluating droplet size, zeta potential, % transmission, and for thermodynamic stability. In vitro dissolution study of FXT loaded L-SNEDDS (batch F7) showed increased dissolution (about 48.54 ± 0.43% in 0.1N HCl while 86.44 ± 0.16% in phosphate buffer pH7.4 within 30min) compared to plain drug (19.65 ± 2.95% in 0.1N HCl while about 17.61 ± 2.63% in phosphate buffer pH7.4 within 30min). Single pass intestinal permeability studies revealed fourfold increase in the intestinal permeability of F7 compared to plain drug. So, for commercial aspects, F7 was further transformed into solid SNEDDS (S-SNEDDS) as readily nanoemulsifying powder form (SNEP) as well as pellets prepared by application of extruder spheronizer. The developed formulation was found superior to pure FXT with enhanced oral bioavailability and anti-gout activity (with reduced uric acid levels), signifying a lipidic system being an efficacious substitute for gout treatment.

Self-nanoemulsifying ramipril tablets: a novel delivery system for the enhancement of drug dissolution and stability.

Background: Ramipril (RMP) suffers from poor aqueous solubility along with sensitivity to mechanical stress, heat, and moisture. The aim of the current study is to improve RMP solubility and stability by designing solid self-nanoemulsifying drug delivery system (S-SNEDDS) as tablet.Methods: The drug was initially incorporated in different liquid formulations (L-SNEDDS) which were evaluated by equilibrium solubility, droplet size, and zeta potential studies. The optimized formulation was solidified into S-SNEDDS powder by the adsorbent Syloid® and compressed into a self-nanoemulsifying tablet (T-SNEDDS). The optimized tablet was evaluated by drug content uniformity, hardness, friability, disintegration, and dissolution tests. Furthermore, pure RMP, optimized L-SNEDDS, and T-SNEDDS were enrolled in accelerated and long-term stability studies.Results: Among various liquid formulations, F5 L-SNEDDS [capmul MCM/transcutol/HCO-30 (25/25/50%w/w)] showed relatively high drug solubility, nano-scaled droplet size, and high negative zeta potential value. The optimized SNEDDS solidification with Syloid® at ratio (1:1) resulted in a compressible powder with an excellent flowability. The optimized tablet (T-SNEDDS) showed accepted content uniformity, hardness, friability, and disintegration time (<15 minutes). The optimized L-SNEDDS, S-SNEDDS, and T-SNEDDS showed superior enhancement of RMP dissolution compared to the pure drug. Most importantly, T-SNEDDS showed significant (P<0.05) improvement of RMP stability compared to the pure drug and L-SNEDDS in both accelerated and long-term stability studies.Conclusion: RMP-loaded T-SNEDDS offers a potential oral dosage form that provides combined improvement of RMP dissolution and chemical stability.

Quality by Design Enabled Development of Oral Self-Nanoemulsifying Drug Delivery System of a Novel Calcimimetic Cinacalcet HCl Using a Porous Carrier: In Vitro and In Vivo Characterisation.

In this present research, work quality by design-enabled development of cinacalcet HCl (CH)-loaded solid self-nanoemulsifying drug delivery system (S-SNEDDS) was conducted using a porous carrier in order to achieve immediate drug release and better oral bioavailability. Capmul MCM (CAP), Tween 20 (TW 20) and Transcutol P (TRP) were selected as excipients. Cumulative % drug release at 30min (Q30), emulsification times (ET), mean globule size (GS) and polydispersity index (PDI) were identified as critical quality attributes (CQAs). Factor mode effect analysis (FMEA) and Taguchi screening design were applied for screening of factors. The optimised single dose of S-SNEDDS obtained using Box-Behnken design (BBD) consisted of 30mg of CH, 50mg of CAP, 149.75mg of TW 20, 55mg of TRP and 260.75mg of Neusilin US2. It showed an average Q30 of 97.6%, ET of 23.3min, GS of 89.5nm and PDI of 0.211. DSC, XRD and SEM predict the amorphous form of S-SNEDDS. In vivo pharmacokinetic study revealed better pharmacokinetic parameters of S-SNEDDS. The above study concluded that the optimised S-SNEDDS is effective to achieve the desired objective. Graphical Abstract.

Novel oral dosage regimen based on self-nanoemulsifying drug delivery systems for codelivery of phytochemicals – Curcumin and thymoquinone

BackgroundCurcumin and Thymoquinone are very well-known phytochemicals for their potent anti-inflammatory and anticancer properties. The major challenges for curcumin is its poor aqueous solubility and erratic oral bioavailability. ObjectiveTo develop a novel liquid self-nanoemulsifying drug delivery system (SNEDDS) containing curcumin and thymoquinone and further converted into a solid dosage form using adsorbents Syloid® and Neusilin® as the solid carrier. MethodsThe characterization of the liquid and solid SNEDDS was performed by particle size & zeta potential analysis, scanning electron microscopy, differential scanning calorimetry, fourier transform infrared spectroscopy and X-ray powder diffraction. The drug loading, and in vitro release studies were carried out to investigate the efficiency of curcumin release from SNEDDS. ResultsThe liquid SNEDDS containing black seed oil showed excellent self-emulsification performance with transparent appearance. The results of characterization studies showed that solidification using 50% (w/w) Syloid® and Neusilin® in the liquid formulation yield free flowing powder with no agglomeration but Neusilin® produced smooth granules than Syloid® and kept the drugs stable in amorphous state. In vitro dissolution studies indicated that liquid SNEDDS formulations of F4 and its solid SNEDDS using Neusilin® provided high dissolution efficiency and reproducibility for curcumin and thymoquinone. However, Neusilin® showed higher rate of dissolution (more than 65%, p < 0.05) compared to Syloid® for curcumin. ConclusionsCurcumin loaded-SNEDDS formulation containing thymoquinone in liquid & solid dosage forms were successfully developed with an increased drug loading and dissolution rate, which could be the potential combined delivery system for various anti-inflammatory and anti-cancer treatments.

Coadministration of Polypeptide-k and Curcumin Through Solid Self-Nanoemulsifying Drug Delivery System for Better Therapeutic Effect Against Diabetes Mellitus: Formulation, Optimization, Biopharmaceutical Characterization, and Pharmacodynamic Assessment.

An attempt has been made to prepare solid self-nanoemulsifying drug delivery system (SNEDDS) of polypeptide-k (PPK) and curcumin (CRM) using Labrafil M1944 CS as oil, Tween-80 as surfactant, Transcutol P as cosurfactant and Aerosil-200 (A-200) as porous hydrophobic carrier for improving their antidiabetic potential through oral delivery. Box-Behnken Design was used to optimize the liquid formulation based on the results of the mean droplet size, polydispersity index, percentage drug loading, and zeta potential. The formulation was adsorbed on Aerosil-200 through spray drying. The formulation showed desirable micromeritic, disintegration, and dissolution properties. About fivefold rise in the dissolution and permeation rate for drugs was observed from formulations vis a vis their unprocessed forms. The formulation was found to be stable with variation in pH, dilution, and temperature. The individual solid SNEDDS formulation of PPK and CRM and their combination were evaluated for antidiabetic potential and the results were compared with their naive forms on streptozotocin-induced diabetic rats. The results revealed better control of serum glucose level and other biochemical tests, such as liver parameters, lipid profiles, and antioxidant levels, as well as histological evaluation of pancreatic tissues in all the solid SNEDDS formulation as compared with their naive forms.

Bioavailability enhanced clopidogrel -loaded solid SNEDDS: Development and in-vitro/in-vivo characterization

The purpose of this study is to develop solid self-nanoemulsifying drug delivery systems (S-SNEDDS) for oral bioavailability enhancement of Clopidogrel (CLP). CLP is an anti-platelet drug used to prevent heart strokes. It suffers from low bioavailability due to extensive hepatic metabolism. Two pseudo-ternary phase diagrams were constructed using different oils, bioenhancing surfactants and co-surfactants. SNEDDS were evaluated for their globule size, polydispersity index and in-vitro drug release. The optimum SNEDDS were adsorbed onto Aeroperl®300 to produce S-SNEDDS. Results showed that SNEDDS-8 (SII8) consisting of 10% Capryol™90, 10% Cremophore®EL and 80% Transcutol®HP possessed the smallest globule size and high % drug release. Furthermore, the optimum S-SNEDDS formula was characterized using differential scanning calorimetry and Fourier Transform Infra-Red which indicated that CLP was molecularly dispersed within the solid nano-system without any signs of interactions. CLP bioavailability in male albino rabbits after oral administration of the optimum CLP-loaded S-SNEDDS formulation compared to the commercially CLP tablets (Plavix®) was investigated. Results revealed that the optimum prepared system exhibited nine folds increment in CLP bioavailability compared to the conventional Plavix® tablets. In conclusion, CLP-loaded S-SNEDDS formulations containing bioenhancing surfactants proved to be a promising approach to improve the oral bioavailability of CLP.

Flurbiprofen-Loaded Solid SNEDDS Preconcentrate for the Enhanced Solubility, In-Vitro Dissolution and Bioavailability in Rats.

The aim of this work was to prepare and optimize a solid self-nanoemulsifying drug delivery system pre-concentrate (SSP) containing water-insoluble flurbiprofen (FL) using a novel pseudo-ternary phase diagram. The pseudo-ternary phase diagram, composed of FL as the drug and dispersion core, Kollisolv MCT 70 as the oil phase, and TPGS (tocopherol polyethylene glycol 1000 succinate) as the surfactant, was constructed for the determination of the SSP region. SSP was investigated in terms of particle size, physical state by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD), in vitro dissolution and oral pharmacokinetics in rats. The determined SSP (FL/Kollisolv MCT 70/TPGS = 10/10/80, weight %) in the pseudo-ternary phase diagram had the melting point of 32.37 °C and uniform mean particle size of below 30 nm without any precipitation of FL in the dispersion. In the dissolution test, the SSP exhibited 95.70 ± 3.40% of release at 15 min, whereas the raw FL showed poor dissolution (i.e., 6.75 ± 1.30%) at that time point. In addition, the SSP showed the enhanced oral absorption (i.e., 1.93-fold increase in AUCinfinite) as compared to the suspension group of raw FL. Therefore, the developed SSP would be a promising drug delivery system with excellent solubilization, dissolution, and bioavailability for FL.