snedds
215733434
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(r) and Neusilin(r) 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.
Molecules
Mohsin Kazi Ahmad Abdul-Wahhab Shahba Saad Alrashoud Majed Alwadei Abdelrahman Y Sherif Fars K Alanazi
211573801
Formulation and evaluation of hyaluronic acid based mucoadhesive self nanoemulsifying drug delivery system (SNEDDS) of tamoxifen for targeting breast cancer.
The present study was intended to develop a papain grafted S protected hyaluronic acid lithocholic acid co block (PAP HA ss LCA) polymeric excipient as an amphiphilic muco permeating stabilizer for targeting breast cancer epithelial cells overexpressed with CD44 receptors. The mucopermeating, stabilizing and targeting capability of the PAP HA ss LCA polymeric excipient was investigated by manufacturing tamoxifen (TMX) loaded self nanoemulsifying drug delivery system (SNEDDS) TMX loaded PAP HA ss LCA incorporated SNEDDS (TMX PAP HA ss LCA SNEDDS) were characterized for their surface chemistry, drug release, permeation enhancement, biocompatibility and antitumor activity. FTIR spectroscopic analysis showed successful synthesis of PAP HA ss LCA polymer. X ray diffraction (XRD) showed the amorphous form of TMX inside SNEDDS. The observed hydrodynamic diameter of TMX PAP HA ss LCA SNEDDS was 367.5 nm. Furthermore, Hyaluronic Acid based Mucoadhesive Self Nanoemulsifying Drug Delivery System (SNEDDS) of TMX showed homogeneity in synthesis with low polydispersity and negative zeta potential due to stabilization with PAP HA ss LCA polymer. The distinct spherical shape of the nanodroplets was evident by transmission electron microscopy (TEM) In vitro release kinetics indicated approximately >80% release within 48 h under sink conditions. Ex vivo permeation study displayed 7.11 folds higher permeation of TMX by TMX PAP HA ss LCA in contrast to pure TMX. The biocompatibility study proved that SNEDDS formulation was safe and compatible against macrophages. In vitro cytotoxicity studies demonstrated that TMX PAP HA ss LCA SNEDDS could efficiently kill MCF 7 breast cancer cells as compared to the native TMX drug. Systemic toxicity studies proved the non toxic nature of TMX PAP HA ss LCA in contrast to pure TMX. Based on these evidences, TMX PAP HA ss LCA SNEDDS formulation seems to be promising mucopermeating, augmented intracellular uptake with strong targeting potential for anti proliferative activity.
International journal of biological macromolecules
Ayesha Batool Rabia Arshad Sobia Razzaq Kainat Nousheen Maria Hassan Kiani Gul Shahnaz
213462200
Towards the development of Self Nano Emulsifying Drug Delivery Systems (SNEDDS) containing trimethyl chitosan for the oral delivery of amphotericin B: In vitro assessment and cytocompatibility studies
Abstract In the current study, a self nanoemulsifying drug delivery system (SNEDDS) containing N trimethyl chitosan chloride (TMC) was developed and evaluated for its potential to deliver amphotericin B (AmpB) via the gastrointestinal tract. SNEDDS comprising Captex 355, Kolliphor RH40 and Propylene Glycol were optimized and characterized for their formation spontaneity, droplet size and drug loading. Investigations on the effects of the application SNEDDS containing TMC to a model intestinal epithelium (Caco 2 monolayer) indicated the capability of the formulations to induce the transient opening of tight junctions. Caco 2 cell viability studies confirmed the safety of the SNEDDS, whereas in vitro transport studies of AmpB through Caco 2 cell monolayers showed the permeation enhancing ability of TMC. Our results suggest that chitosan derivative TMC combined with a SNEDDS may be used as permeation enhancer to facilitate oral delivery of AmpB.
Eleni Kontogiannidou Thomas Meikopoulos Christina Virgiliou Nikolaos Bouropoulos Helen G Gika Ioannis S Vizirianakis Anette Mullertz Dimitrios G Fatouros
142981782
Evaluation of Self Nanoemulsifying Drug Delivery Systems (SNEDDS) for Poorly Water Soluble Talinolol: Preparation, in vitro and in vivo Assessment
Objective The aim of this study was to investigate the in vitro and in vivo performance of self nanoemulsifying drug delivery systems (SNEDDSs) of talinolol (TAL) a poorly water soluble drug. Methods Self nanoemulsifying drug delivery systems of TAL were prepared using various oils, non ionic surfactants and/or water soluble co solvents and assessed visually/by droplet size measurement. Equilibrium solubility of TAL in the anhydrous and diluted SNEDDS was conducted to achieve the maximum drug loading. The in vitro dissolution experiments and human red blood cells (RBCs) toxicity test, ex vivo gut permeation studies, and bioavailability of SNEDDS in rats were studied to compare the representative formulations with marketed product Cordanum(r) 50 mg and raw drug. Results The results from the characterization and solubility studies showed that SNEDDS formulations were stable with lower droplet sizes and higher TAL solubility. From the dissolution studies, it was found that the developed SNEDDS provided significantly higher rate of TAL release >97% in 2.0 h) compared to raw TAL and marketed product Cordanum(r) The RBC lysis test suggested negligible toxicity of the formulation to the cells. The ex vivo permeability assessment and in vivo pharmacokinetics study of a selected SNEDDS formulation (F6) showed about four fold increase in permeability and 1.58 fold enhanced oral bioavailability of TAL in comparison to pure drug, respectively. Conclusion Talinolol loaded SNEDDS formulations could be a potential oral pharmaceutical product with high drug loading capacity, improved drug dissolution, increased gut permeation, reduced/no human RBC toxicity, and enhanced oral bioavailability.
Front. Pharmacol.
Mohsin Kazi Mohammed Al-Swairi Ajaz Ahmad Mohammad Raish Fars K Alanazi Mohamed M Badran Azmat Ali Khan Amer M Alanazi Muhammad Delwar Hussain
213876411
Encapsulation of an insulin modified phosphatidylcholine complex in a self nanoemulsifying drug delivery system (SNEDDS) for oral insulin delivery
Abstract Insulin is a dimeric hormone commonly administered by subcutaneous injection as the primary treatment for diabetes. This strategy, while efficient, does carry potential complications i.e. lipodystrophy with a decrease in absorption and also possible infections, caused by constant injectable punctures or lack of hygiene measures at the time of administration. Unfortunately, orally administered insulin has low bioavailability. In the present study we developed a complex based on insulin and modified or unmodified phosphatidylcholine, in order to encapsulate the hormone in a self nanoemulsifying drug delivery system (SNEDDS) incorporating 2.5% (w t% of the complex and managing to form nanoemulsions with particle sizes of 20 44 nm. SNEDDS were subjected to in vitro gastrointestinal conditions, showing a 35.7% bioavailability upon reaching the final phase of the simulated small intestine. In an in vivo study, Wistar rats with induced diabetes showed a 36.1% reduction in blood glucose levels after 4 h of administering the modified phospholipid SNEDDS, and a 1.8% bioavailability with respect to the subcutaneous application of insulin.
Diego A Bravo-Alfaro Maria O F Munoz-Correa Dalia Santos-Luna Jorge F Toro-Vazquez Cynthia Cano-Sarmiento Rebeca Garcia-Varela Hugo S Garcia
211134595
Voriconazole loaded self nanoemulsifying drug delivery system (SNEDDS) to improve transcorneal permeability
Abstract The aim of this study was to develop self nanoemulsifying drug delivery system (SNEDDS) to improve the transcorneal permeability of voriconazole. A 'mixture design around a reference mixture' approach was applied. This latter included four components, namely, isopropyl myristate, PEG 400, Tween(r) 80 and Span(r) 80 as oil, co solvent, surfactant and co surfactant, respectively. Droplet size was selected as response. The effect of mixture components on droplet size was analyzed by means of response trace method. Optimal formulation was subjected to stability studies and characterized for droplet size, polydispersity index (PDI) pH, osmolarity, viscosity and percentage of transmittance. Ex vivo transcorneal permeation of the optimal and the marketed formulations was carried out on excised bovine cornea using Franz cell diffusion apparatus. Optimal voriconazole loaded SNEDDS showed moderate emulsification efficiency and was characterized by a droplet size of 21.447 0.081 nm, a PDI of 0.156 0.004, a pH of 7.205 0.006, an osmolarity of 310 mosmol/Kg and a viscosity of 8.818 0.076 cP. Moreover, it presented an excellent stability and exhibited a significant improvement (p 0.05) in apparent permeability coefficient (1.982 0.187 x 10 6 cm/s) when compared to commercialized formulation (1.165 0.106 x 10 6 cm/s) These results suggest that SNEDDS is a promising carrier for voriconazole ocular delivery.
Pharmaceutical development and technology
Bakoliarisoa Nivomalala Voahangy Rasoanirina Mohamed Ali Lassoued Amel Kamoun Badr Bahloul Karim Miladi Souad Bannour Ep Sfar
220851622
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 mM. 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.
Pharmaceuticals
Alaa Alghananim Yildiz Ozalp Burcu Mesut Nedime Serakinci Yildiz Ozsoy Sevgi Gungor
221127760
Enhancing Oral Bioavailability of Apigenin Using a Bioactive Self Nanoemulsifying Drug Delivery System (Bio SNEDDS) In Vitro, In Vivo and Stability Evaluations
Apigenin (APG) is a very well known flavonoid for its anti inflammatory and anticancer properties. The purpose of this study is to improve the solubility and bioavailability of APG using a stable bioactive self nanoemulsifying drug delivery system (Bio SNEDDS) APG was incorporated in an oil phase comprising coconut oil fatty acid, Imwitor 988, Transcutol P, and HCO30 to form a Bio SNEDDS. This preparation was characterized for morphology, particle size, and transmission electron microscopy (TEM) The APG performance was investigated in terms of loading, precipitation, release and stability tests from the optimal Bio SNEDDS. An antimicrobial test was performed to investigate the activity of the Bio SNEDDS against the selected strains. Bioavailability of the Bio SNEDDS was evaluated using Wister rats against the commercial oral product and the pure drug. The results demonstrated the formation of an efficient nanosized (57 nm) Bio SNEDDS with a drug loading of 12.50 mg/gm which is around 500 fold higher than free APG. TEM analysis revealed the formation of spherical and homogeneous nanodroplets of less than 60 nm. The dissolution rate was faster than the commercial product and was able to maintain 90% APG in gastro intestinal solution for more than 4 h. A stability study demonstrated that the Bio SNEDDS is stable at a harsh condition. The in vivo pharmacokinetics parameters of the Bio SNEDDS formulation in comparison to the pure drug showed a significant increase in maximum concentration (Cmax) and area under the curve (AUC (0 t) of 105.05% and 91.32% respectively. Moreover, the antimicrobial study revealed moderate inhibition in the bacterial growth rate. The APG Bio SNEDDS could serve as potential carrier aimed at improving the clinical application of APG.
Pharmaceutics
Mohsin Kazi Abdullah Alhajri Sultan M Alshehri Ehab Mostafa Elzayat Osaid T Al Meanazel Faiyaz Shakeel Omar M Noman Mohammad A Altamimi Fars K Alanazi
219921735
Formulation and evaluation of luteolin supersaturatable self nanoemulsifying drug delivery system (S SNEDDS) for enhanced oral bioavailability
Abstract The current investigation was aimed to enhance the solubility and oral bioavailability of luteolin by employing the supersaturable self nanoemulsifying drug. delivery system(S SNEDDS) The formulation for SNEDDS consisted of caprylic/capric triglyceride, polyoxyl 35 hydrogenated castor oil and polyethylene glycol 400 in a ratio of 20.1:48.2:31.7 by weight, which was determined and optimized based on solubility studiesstudies, pseudo ternary phase diagrams and central composite design. Hydroxypropyl methylcellulose (HPMC) K4M at a 2% mass ratio was determined to be the optimal precipitation inhibitor for luteolin loaded SNEDDS according to in vitro precipitation experiments. Luteolin S SNEDDS formed clarified nanoemulsion with a particle size of 25.60 nm and a zeta potential of 10.2 mV after dilution. The interaction between luteolin and HPMC K4M was measured by powder X ray diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy and 1H NMR spectroscopy. Moreover, S SNEDDS achieved an excellent in vitro dissolution of 99% in phosphate buffer at pH 6.8 with 0.5% Tween 80. The in vivo pharmacokinetics study of S SNEDDS showed a significant increase (2.2 fold) in the oral bioavailability of luteolin in rats compared to that of the conventional SNEDDS. In summary, these observations illustrated the application prospects of S SNEDDS technology in promoting solubility and oral bioavailability from poorly water soluble drugs, at least for luteolin.
Nan Zhang Fei Zhang Shuo Xu Kaiqing Yun Wenjing Wu Weisan Pan
220773209
Enhanced oral bioavailability and neuroprotective effect of fisetin through its SNEDDS against rotenone induced Parkinson's disease rat model.
Fisetin (FS) was reported to have various pharmacological activities. But due to its lower aqueous solubility and oral bioavailability, it is not in much use. As solubility and bioavailability plays and important role in the pharmacological activity, in this research work we tried to improve the oral bioavailability of fisetin. In this research work, we developed self nanoemulsifying drug delivery system (SNEDDS) of fisetin. Developed SNEDDS were subjected for pharmacokinetic and pharmacodynamics studies against rotenone induced Parkinson's disease (PD) model in rats. Higher Cmax and area under the curve during pharmacokinetic study indicated that SNEDDS improved the oral bioavailability of FS and also increased the mean residence time of drug in plasma. Results of behavior parameters (locomotor, muscle co ordination and catalepsy) biochemical estimation (TBARS, nitrite, GSH, SOD and CAT) and ELISA (soluble alfa synuclein, BDNF, TNF a and IL 6) confirmed the significantly improved (p<0.05) neuroprotection in rats treated with FS loaded SNEDDS as compared to rats treated with naive FS. This study suggests that SNEDDS improved the oral bioavailability of FS which further helped in improving its neuroprotective activity in rat model of PD. It further suggests the potential use of FS SNEDDS in effective management of PD condition.
Food and chemical toxicology an international journal published for the British Industrial Biological Research Association
Navneet Khurana Sachin Kumar Singh Shelly Khurana Bhupinder Kapoor Manish Vyas Rubiya Khursheed Ankit Awasthi Jaskiran Kaur Leander Corrie