Solid Self-nanoemulsifying Drug Delivery System Research Articles

Self-nanoemulsifying drug delivery system (SNEDDS) of docetaxel and carvacrol synergizes the anticancer activity and enables safer toxicity profile: optimization, and in-vitro, ex-vivo and in-vivo pharmacokinetic evaluation.

Docetaxel (DTX) is a first-line chemotherapeutic molecule with a broad-spectrum anticancer activity. On the other hand, carvacrol (CV) has anti-inflammatory, antioxidant, cytotoxic, and hepatoprotective properties that could reduce undue toxicity caused by DTX chemotherapy. Thus, in order to overcome the challenges posed by DTX's poor aqueous solubility, low permeability, hepatic first pass, and systemic toxicities, we have developed a novel solid self-nanoemulsifying drug delivery system (S-SNEDDS) co-loaded with DTX and CV. In the present investigation, liquid-SNEDDS (L-SNEDDS) were fabricated using Nigella sativa oil, Cremophor RH 40, and Ethanol which was converted into solid by lyophilization using Aerosil 200. The reconstituted CV-DTX-S-SNEDDS showed an average globule size of < 200nm with promising flow properties (angle of repose θ: 33.22 ± 0.06). Additionally, 2.3-fold higher dissolution of DTX was observed from CV-DTX-S-SNEDDS after 6h as compared to free DTX. Similar trend was followed in dialysis release experiments with 1.5-fold higher release within 24h. Ex vivo permeation studies demonstrated significantly increased permeation of 1077.02 ± 12.72μg/cm2 of CV-DTX-S-SNEDDS after 12h. In vitro cell cytotoxicity studies revealed 5.2-fold reduction in IC50 as compared to free DTX in MDA-MB-231 cells. Formulation was able to induce higher apoptosis in cells treated with CV-DTX-S-SNEDDS as compared to free DTX and CV. It was evident from toxicity studies that CV-DTX-S-SNEDDS was well tolerated at higher dose where CV was able to manage the toxic effects of free DTX. In vivo pharmacokinetic study showed 3.4-fold increased Cmax and improved oral bioavailability as compared to free DTX. Thus, CV-DTX-S-SNEDDS could be an encouraging option for facilitating DTX oral therapy.

Development of a sorafenib-loaded solid self-nanoemulsifying drug delivery system: Formulation optimization and characterization of enhanced properties.

Sorafenib, marketed under the brand name Nexavar®, is a multiple tyrosine kinase inhibitor drug that has been actively used in the clinical setting for the treatment of several cancers. However, the low solubility and bioavailability of sorafenib constitute a significant barrier to achieving a good therapeutic outcome. We developed a sorafenib-loaded self-nanoemulsifying drug delivery system (SNEDDS) formulation composed of capmul MCM, tween 80, and tetraglycol, and demonstrated that the SNEDDS formulation could improve drug solubility with excellent self-emulsification ability. Moreover, the sorafenib-loaded SNEDDS exhibited anticancer activity against Hep3B and KB cells, which are the most commonly used hepatocellular carcinoma and oral cancer cell lines, respectively. Subsequently, to improve the storage stability and to increase the possibility of commercialization, a solid SNEDDS for sorafenib was further developed through the spray drying method using Aerosil® 200 and PVP K 30. X-ray diffraction and differential scanning calorimeter data showed that the crystallinity of the drug was markedly reduced, and the dissolution rate of the drug was further improved in formulation in simulated gastric and intestinal fluid conditions. In vivo study, the bioavailability of the orally administered formulation increases dramatically compared to the free drug. Our results highlight the use of the solid-SNEDDS formulation to enhance sorafenib's bioavailability and outlines potential translational directions for oral drug development.

Investigation of In Vivo Bioavailability Enhancement of Iloperidone-Loaded Solid Self-Nanoemulsifying Drug Delivery Systems: Formulation and Optimization Using Box-Behnken Design and Desirability Function

Investigation of In Vivo Bioavailability Enhancement of Iloperidone-Loaded Solid Self-Nanoemulsifying Drug Delivery Systems: Formulation and Optimization Using Box-Behnken Design and Desirability Function

Adsorbent Precoating by Lyophilization: A Novel Green Solvent Technique to Enhance Cinnarizine Release from Solid Self-Nanoemulsifying Drug Delivery Systems (S-SNEDDS).

Solidification by high surface area adsorbents has been associated with major obstacles in drug release. Accordingly, new approaches are highly demanded to solve these limitations. The current study proposes to improve the drug release of solidified self-nanoemulsifying drug delivery systems (SNEDDS) to present dual enhancement of drug solubilization and formulation stabilization, using cinnarizine (CN) as a model drug. The solidification process involved the precoating of adsorbent by lyophilization of the aqueous dispersion of polymer-adsorbent mixture using water as a green solvent. Then, the precoated adsorbent was mixed with drug-loaded liquid SNEDDS to prepare solid SNEDDS. The solid-state characterization of developed cured S-SNEDDS was done using X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC). In vitro dissolution studies were conducted to investigate CN SNEDDS performance at pH 1.2 and 6.8. The solidified formulations were characterized by Brunauer-Emmett-Teller (BET), powder flow properties, scanning electron microscopy, and droplet size analysis. In addition, the optimized formulations were evaluated through in vitro lipolysis and stability studies. The cured solid SNEDDS formula by PVP k30 showed acceptable self-emulsification and powder flow properties. XRD and DSC revealed that CN was successfully amorphized into drug-loaded S-SNEDDS. The uncured solid SNEDDS experienced negligible drug release (only 5% drug release after 2 h), while the cured S-SNEDDS showed up to 12-fold enhancement of total drug release (at 2 h) compared to the uncured counterpart. However, the cured S- SNEDDS showed considerable CN degradation and decrease in drug release upon storage in accelerated conditions. The implemented solidification approach offers a promising technique to minimize the adverse effect of adsorbent on drug release and accomplish improved drug release from solidified SNEDDS.

Optimized L-SNEDDS and spray-dried S-SNEDDS using a linked QbD-DM3 rational design for model compound ketoprofen

A QbD-DM3 strategy was used to design ketoprofen (KTF) optimized liquid (L-SNEDDS) and solid self-nanoemulsifying drug delivery systems (S-SNEDDS). Principal component analysis was used to identify the optimized L-SNEDDS containing Capmul® MCM NF, 10 % w/w; Kolliphor® ELP, 60 % w/w; and propylene glycol, 30 % w/w. The S-SNEDDS was manufactured by spray-drying a feed dispersion prepared by dissolving the optimized KTF-loaded L-SNEDDS in an ethanol-Aerosil® 200 dispersion. A Box Behnken design was employed to evaluate the effect of drug concentration (DC), Aerosil® 200 concentration (AC) and feed rate (FR) on maximizing percent yield (PY) and loading efficiency (LE). The optimal levels of DC, AC, and FR were 19.9 % w/w, 30.0 % w/w, and 15.0 %, respectively. The optimized S-SNEDDS was amorphous, and its dissolution showed a 2.37-fold increase in drug release compared to KTF in 0.1 HCl. An optimized independent spray-dried S-SNEDDS verification batch showed that the predicted and observed PY and LE were 70.49 % and 92.49 %, and 70.02 % and 91.27 %, respectively. The optimized L-SNEDDS and S-SNEDDS also met their quality target product profile criteria for globule size <100 nm, polydispersity index < 0.400, emulsification time < 30 s, and KTF L-SNEDDS solubility 100-fold greater than its water solubility.

Multivariate Data Analysis and Central Composite Design-Oriented Optimization of Solid Carriers for Formulation of Curcumin-Loaded Solid SNEDDS: Dissolution and Bioavailability Assessment.

The study was initiated with two major purposes: investigating the role of isomalt (GIQ9) as a pharmaceutical carrier for solid self-nanoemulsifying drug delivery systems (S-SNEDDSs) and improving the oral bioavailability of lipophilic curcumin (CUN). GIQ9 has never been explored for solidification of liquid lipid-based nanoparticles such as a liquid isotropic mixture of a SNEDDS containing oil, surfactant and co-surfactant. The suitability of GIQ9 as a carrier was assessed by calculating the loading factor, flow and micromeritic properties. The S-SNEDDSs were prepared by surface adsorption technique. The formulation variables were optimized using central composite design (CCD). The optimized S-SNEDDS was evaluated for differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), microscopy, dissolution and pharmacokinetic studies. The S-SNEDDS showed a particle size, zeta potential and PDI of 97 nm, -26.8 mV and 0.354, respectively. The results of DSC, XRD, FTIR and microscopic studies revealed that the isotropic mixture was adsorbed onto the solid carrier. The L-SNEDDS and S-SNEDDS showed no significant difference in drug release, indicating no change upon solidification. The optimized S-SNEDDS showed 5.1-fold and 61.7-fold enhancement in dissolution rate and oral bioavailability as compared to the naïve curcumin. The overall outcomes of the study indicated the suitability of GIQ9 as a solid carrier for SNEDDSs.

Development of Guar Gum-Pectin-Based Colon Targeted Solid Self-Nanoemulsifying Drug Delivery System of Xanthohumol.

Present study deciphers development of oral polysaccharide-based colon targeted solid self-nanoemulsifying drug delivery system (S-SNEDDS) of xanthohumol (XH). Several studies have shown that XH has anti-inflammatory and antioxidant properties, suggesting that it could be a good candidate for the treatment of colorectal diseases (CRD). Despite its potential, XH has a low aqueous solubility. As a result, its bioavailability is constrained by the dissolution rate. The liquid (L)-SNEDDS was constituted using Labrafac PG as oil, Tween 80 as surfactant and Transcutol P as co-surfactant. The L-SNEDDS was then adsorbed onto the surface of guar gum and pectin and developed into S-SNEDDS powder. Ternary phase diagram was used to optimize the process of developing L-SNEDDS. The formulation showed mean droplet size of 118.96 ± 5.94 nm and zeta potential of -19.08 ± 0.95 mV and drug loading of 94.20 ± 4.71%. Dissolution studies carried out in medium containing rat caecal contents (RCC) represented the targeted release of S-SNEDDS powder. It was observed that S-SNEDDS showed less than 10% release XH in initial 5 h and rapid release occurred between the 5th and 10th hour. Results of cytotoxicity studies revealed good cytotoxicity of XH loaded S-SNEDDS for Caco2 cells as compared to raw-XH.

Polysaccharide, fecal microbiota, and curcumin-based novel oral colon-targeted solid self-nanoemulsifying delivery system: formulation, characterization, and in-vitro anticancer evaluation

The use of polysaccharides in preparation of microbially triggered colon-targeted delivery system has been explored extensively to deliver drugs at the colonic site. This type of targeting is attributed to inherent property of polysaccharides by virtue of which they are digested in the gut only by the colonic microflora. In last two decades, the use of fecal microbiota transplantation (FMT) has been reported widely to treat colonic diseases such as Crohn's disease, irritable bowel syndrome, and recurrent Clostridium difficile infection. It has been established that FMT downregulates inflammatory proliferation and pro carcinogenic pathways. Although a few reports exist on the use of colon-targeted FMT capsules in increasing the microbial diversity of gut microflora, they have not been able to establish clinical superiority of the colon-targeted capsules over conventional orally administered capsules. Hence, in the present study, an attempt has been made to utilize a multipronged strategy through a single formulation, wherein an anticancer phytoconstituent, polysaccharides, fecal microbiota extract (FME), and nanodelivery systems have been designed for the effective treatment of colon cancer. Overall, the study is aimed toward the development of an oral colon-targeted solid self-nanoemulsifying drug delivery system (S-SNEDDS) in which curcumin (CCM) was loaded. These SNEDDS were added to polysaccharide mixture of guar gum, pectin, lactose along with aerosol 200 (A-200) and then to the slurry of fecal microbiota extract. The liquid was then freeze dried and developed into solid SNEDDS powder. The process of formulating liquid SNEDDS was optimized using ternary phase diagram and Box Behnken Design. The developed formulation was characterized for physicochemical, physicomechanical, drug release and cytotoxic potential studies. The droplet size of reconstituted S-SNEDDS was found to be 78.46 ± 0.87 nm. The site-specific release of S-SNEDDS powder was confirmed by dissolution studies in medium containing rat caecal contents, wherein, the formulation containing guar gum and pectin in 1% w/w ratio showed less than 10% drug release in initial 5 h and burst release between 5th and 10th h indicating colon-specific release of CCM. Significant cytotoxic effect was seen for CCM-loaded S-SNEDDS as compared to control formulations. The use of 16s metagenomic technique confirmed no significant change in fecal microbiota composition of formulation pre- and postlyophilization. Overall, the study suggested a novel, oral colon-targeted SNEDDS-based formulation containing fecal microbiota and CCM for the treatment of colon cancer.

Preparation of Solid Self-Nanoemulsifying Drug Delivery Systems (S-SNEDDS) by Co-Extrusion of Liquid SNEDDS and Polymeric Carriers-A New and Promising Formulation Approach to Improve the Solubility of Poorly Water-Soluble Drugs.

The present study focused on a new formulation approach to improving the solubility of drugs with poor aqueous solubility. A hot melt extrusion (HME) process was applied to prepare drug-loaded solid self-nanoemulsifying drug delivery systems (S-SNEDDS) by co-extrusion of liquid SNEDDS (L-SNEDDS) and different polymeric carriers. Experiments were performed with L-SNEDDS formulations containing celecoxib, efavirenz or fenofibrate as model drugs. A major objective was to identify a polymeric carrier and process parameters that would enable the preparation of stable S-SNEDDS without impairing the release behavior and storage stability of the L-SNEDDS used and, if possible, even improving them further. In addition to commercially available (co)polymers already used in the field of HME, a particular focus was on the evaluation of different variants of a recently developed aminomethacrylate-based copolymer (ModE) that differed in Mw. Immediately after preparation, the L-SNEDDS and S-SNEDDS formulations were tested for amorphicity by differential scanning calorimetry. Furthermore, solubility and dissolution tests were performed. In addition, the storage stability was investigated at 30 °C/65% RH over a period of three and six months, respectively. In all cases, amorphous formulations were obtained and, especially for the model drug celecoxib, S-SNEDDS were developed that maintained the rapid and complete drug release of the underlying L-SNEDDS even over an extended storage period. Overall, the data obtained in this study suggest that the presented S-SNEDDS approach is very promising, provided that drug-loaded L-SNEDDS are co-processed with a suitable polymeric carrier. In the case of celecoxib, the E-173 variant of the novel ModE copolymer proved to be a novel polymeric carrier with great potential for application in S-SNEDDS. The presented approach will, therefore, be pursued in future studies to establish S-SNEDDS as an alternative formulation to other amorphous systems.

FORMULATION AND EVALUATION OF SOLID-SUPERSATURABLE-SNEDDS OF IBRUTINIB

Objective: The aim of current research is to develop a solid supersaturable self-nanoemulsifying drug delivery system (S-SNEDDS) of ibrutinib for enhancing the solubility and Bioavailability. Methods: Crossential O 94–Croduret 40SS–carbitol are chosen based on the maximum solubility of ibrutinib and were used to construct ternary phase diagrams with Smix in 3:1 ratio and 70 mg drug loading was done and evaluated for particle size, zeta potential, polydispersity index, entrapment efficiency, drug content and in vitro drug release. Final optimised one is characterised for FTIR, DSC, stability studies and in-vivo studies in rats. To choose a precipitation inhibitor, in vitro precipitation studies were carried out, and supersaturable SNEDDS were made the prepared formulations were evaluated for micromertitic properties and the final optimised one is characterized for FTIR, DSC, SEM and stability studies. Results: Out of all formulations, F15 exhibited good results with the highest drug release of 98.25% in 60 min. LSS9 with 3% HPMC E4M as the best precipitation inhibitor (PPI) exhibited the smallest droplet size of 65.4 nm, a zeta potential of-17.7 mV, and a PDI of 0.453. SSS1 with magnesium trisilicate as an adsorbent showed best flow characteristics and the highest drug content of 99.72%. The DSC, FT-IR and stability studies confirmed the complexation of ibrutinib and amorphous state of the drug and formulation to be stable for 3 mo. Cmax of the solid supersaturable SNEDDS 139.42±2.16 mg/l was significant (p&lt;0.05) as compared to the pure drug suspension formulation 38.15±1.46 mg/l. Tmax of solid supersaturable SNEDDS formulation and pure drug suspension was 1.00±0.06 h and 1.50±0.02h, respectively. Statistically, AUC of the solid supersaturable SNEDDS formulation was significantly higher (p&lt;0.05) as compared to pure drug suspension formulation. Conclusion: Thus, this study indicated that the solid SNEDDS could be used as a potential drug carrier for ibrutinib with improved solubility and and bioavailability.

Solubility Enhancement of Poorly Soluble Drug Ezetimibe by Developing Self Nano Emulsifying Drug Delivery System

Objectives: To enhance solubility, dissolution, and permeability of poorly water-soluble drug Ezetimibe (EZE) using a self-nano emulsifying drug delivery system (SNEDDS). Methods: Initially, the solubility of the EZE was determined in various oils and buffers. Surfactants and co-surfactants were screened based on the solubility of the drug in oil as per the emulsification efficacy test. Liquid SNEDDS was developed and characterized. Solid SNEDDS was developed and characterized using optimized liquid SNEDDS followed by the development of EZE-loaded Tablet SNEDDS. Finding: Liquid SNEDDS (LSNEDDS) was formulated using Capmul MCM C8 EP, Cremophore RH 40, and Labrafil M 2125 CS as oil, surfactant, and co-surfactant respectively. Optimized L-SNEDDS formulation was found to be efficient with an average %T of 99.5%, drug content of 98.43%, flask inversion 0 numbers, and the average particle size of 36.7 nm, zeta potential of -57.5 mV, Polydispersibility index in of 0.119. Also, the in vitro release profile of drug from L-SNEDDS encapsulated in hard gelatin capsules was evaluated in different dissolution media viz. simulated gastric fluid and simulated intestinal fluid. For the drug, more than 95% cumulative release was observed within 30 min exclusive of the pH of the medium. The L-SNEDDS were adsorbed on a solid support and then mixed with tablet blends and compressed into tablets. Further, no adverse changes in globule size, shape, the zeta potential of SNEDDS, and dissolution profile were apparent on conversion to solid powder form and tablet form. Novelty: The developed liquid SNEDDS form of EZE showed enhanced solubility, dissolution, and permeability in comparison to pure drugs. Conversion of L-SNEDDS to PSNEDDS would be a novel approach to overcome the limitations associatedwith liquid dosage forms. Keywords: Ezetimibe (EZE); Selfnano emulsifying drug delivery system (SNEDDS); liquid SNEDDS (L SNEDDS); powder SNEDDS (PSNEDDS); Tablet SNEDDS (TSNEDDS)

Development and Characterization of Celecoxib Solid Self-nanoemulsifying Drug Delivery Systems (S-SNEDDS) Prepared Using Novel Cellulose-Based Microparticles as Adsorptive Carriers

Self-nanoemulsifying drug delivery systems (SNEDDS) represent an interesting platform for improving the oral bioavailability of poorly soluble lipophilic drugs. While Liquid-SNEDDS (L-SNEDDS) effectively solubilize the drug in vivo, they have several drawbacks, including poor storage stability. Solid-SNEDDS (S-SNEDDS) combine the advantages of L-SNEDDS with those of solid dosage forms, particularly stability. The aim of the present study was to convert celecoxib L-SNEDDS into S-SNEDDS without altering their release behavior. Various commercially available adsorptive carrier materials were investigated, as well as novel cellulose-based microparticles prepared by spray drying from an aqueous dispersion containing Diacel® 10 and methyl cellulose or gum arabic as a binder prior to their use. Particle size and morphology of the carrier materials were screened by scanning electron microscopy and their effects on the loading capacity for L-SNEDDS were investigated, and comparative in vitro dissolution studies of celecoxib L-SNEDDS and the different S-SNEDDS were performed immediately after preparation and after 3 months of storage. Among the adsorptive carrier materials, the novel cellulose-based microparticles were found to be the most suitable for the preparation of celecoxib S-SNEDDS from L-SNEDDS, enabling the preparation of a solid, stable formulation while preserving the in vitro release performance of the L-SNEDDS formulation.

Development and exploration on flowability of solid self-nanoemulsifying drug delivery system of morin hydrate

• Solid SNEDDS of MH was prepared by physical adsorption method. • Flowability of solid SNEDDS was investigated by powder flow tester. • Solid state characterization confers transformation of crystalline to amorphous. • In vitro- In vivo studies revealed an improvement of dissolution & bioavailability. • The estimated shelf life of solid SNEDDS of MH was found to be 27.57 months. Morin hydrate (MH) is a promising flavonoid with diverse biological activities; unfortunately, it finds limited clinical application due to its low water solubility. Herein, we developed a liquid self nano-emulsifying drug delivery system ( l -SNEDDS) employing Labrafil M 1994 CS, Cremophor RH 40, and Transcutol HP. The l -SNEDDS has been solidified by physical adsorption using inert carriers, i.e., Neusilin US2 and Aerosil 200. The S-SNEDDS was thoroughly investigated for flow function (FF), effective angle of wall friction (EAWF), and effective angle of internal friction (EAIF) employing a powder flow tester (PFT). The solid-state characterizations of S-SNEDDS were performed using FTIR, DSC, PXRD, and SEM. Further, in vitro dissolution, in vivo pharmacokinetic, and shelf life estimation were performed on selected SOF-2 formulation. The SOF-2 reveals good emulsifying ability, particle size (52 ± 4.25 nm), and PDI (0.133 ± 0.06). The FF and Jenike’s classification suggests the “free-flowing” nature of S-SNEDDS prepared using Neusilin US2. Further, S-SNEDDS prepared using Neusilin US2 showed a low friction angle, i.e., EAWF and EAIF, than Aerosil 200, therefore, a better flowability. The solid-state characterization of SOF-2 demonstrated the transition of MH from crystalline to amorphous state and good compatibility between MH and Neusilin US2. Further, SOF-2 showed more dissolution than pure MH and subsequently 2.97-fold increments in its oral bioavailability. Moreover, the shelf life of SOF-2 was reported to be 27.57 months, suggesting its excellent physical and chemical stability. In brief, solidifying l -SNEDDS and investigating flow behaviors by PFT could find attention in the pharmaceutical and food industry for commercial purposes.

Solid Self-Nano Emulsifying Nanoplatform Loaded with Tamoxifen and Resveratrol for Treatment of Breast Cancer.

The solid self-nanoemulsifying drug delivery system (s-SNEDDS) is a growing platform for the delivery of drugs via oral route. In the present work, tamoxifen (TAM) was loaded in SNEDDS with resveratrol (RES), which is a potent chemotherapeutic, antioxidant, anti-inflammatory and P-gp inhibitor for enhancing bioavailability and to obtain synergistic anti-cancer effect against breast cancer. SNEDDS were developed using capmul MCM as oil, Tween 80 as surfactant and transcutol-HP as co-surfactant and optimized by central composite rotatable design. Neusilin US2 concentration was optimized for adsorption of liquid SNEDDS to prepare s-SNEDDS. The developed formulation was characterized and investigated for various in vitro and cell line comparative studies. Optimized TAM-RES-s-SNEDDS showed spherical droplets of a size less than 200 nm. In all in vitro studies, TAM-RES-s-SNEDDS showed significantly improved (p ˂ 0.05) release and permeation across the dialysis membrane and intestinal lumen. Moreover, TAM-RES-s-SNEDDS possessed significantly greater therapeutic efficacy (p < 0.05) and better internalization on the MCF-7 cell line as compared to the conventional formulation. Additionally, oral bioavailability of TAM from SNEDDS was 1.63 folds significantly higher (p < 0.05) than that of combination suspension and 4.16 folds significantly higher (p < 0.05) than TAM suspension. Thus, findings suggest that TAM- RES-s-SNEDDS can be the future delivery system that potentially delivers both drugs to cancer cells for better treatment.

Impact on HDL and LDL of Hyperlipidemic Rat Models: Designed Solid Self-Nanoemulsifying Drug Delivery Systems with Atorvastatin and Ezetimibe combination

The main purpose of this study was to develop and evaluate solid self-nanoemulsifying drug delivery systems (S-SNEDDs) of Atorvastatin/ Ezetimibe combination to combine the advantages of liquid SNEDDs with those of solid dosage forms and investigate the effect of solidification on both lipid lowering efficiency and the ability to enhance oral bioavailability of included poorly water soluble drugs. Spray dried solid powder was prepared using Aerosil 200 based on its high adsorption capacity and the ratio of liquid SNEDDs: Aerosil was (4:1) due to the smaller droplet size produced after reconstitution compared to other ratios. Surface morphology characteristics and drug-excipients interactions were evaluated via Scanning Electron Microscopy (SEM) and Fourier Transformed Infrared Spectroscopy (FTIR). Crystallinity nature affect drug dissolution so, it was determined by Differential Scanning Calorimetry (DSC) and Powder X-ray Diffraction (PXRD). Pharmacokinetic study investigated the ability of (S-SNEDDS) to improve oral bioavailability of included drugs while, pharmacodynamic study evaluate its efficiency to control serum cholesterol levels compared to pure drugs suspension and liquid SNEDDs. Solid spray dried powder showed very good flowability (3.41±0.23g/s) and rapid dispersion in water with maintaining the self-emulsifying efficiency of liquid formula. Physicochemical evaluation of powder showed spherical separated particles with no significant drug-excipients interactions and drugs are molecularly dispersed or in amorphous state that improve dissolution rate as proven by in-vitro release studies. Pharmacokinetic and pharmacodynamic studies proved that the solidification process had no remarkable effect on the efficiency of liquid formula to enhance oral bioavailability of incorporated drugs and control serum cholesterol level compared to pure drugs suspension. S-SNEDDS was proved as efficient candidate to improve oral bioavailability of Atorvastatin / Ezetimibe combination and control cholesterol serum levels.

Preparation and Characterization of Advanced Nano medicine For Malaria: Box Behnken Design Approach

In tropical countries, malaria is a larger cause of sickness and death in adults and children. Drug resistance with antimalarial therapy has now become a serious problem worldwide and it is the basic reason for the need of combination therapy. Artemisinin-based combination therapy (ACT) is widely used nowadays. The drugs selected for the study from ACT were an Artesunate (AST) and Lumefantrine (LUM). In this study, the optimized Solid-Self nanoemulsifying drug delivery system (S-SNEDDS) formulation of AST and LUM was developed using Box Behnken design (BBD) which showed greater in-vitro drug release when compared to marketed formulation. Both the drugs AST and LUM show high solubility in Anise oil, Tween 80 (surfactant), and PEG 400 (co-surfactant). Ternary phase diagrams were used to select nanoemulsifying regions. It was found to have a maximum nanoemulsion region with a 2:1 surfactant to co-surfactant ratio. The effect of formulation variables was studied by BBD. Thirteen formulations were prepared and were further characterized based on globule size, PDI, zeta potential, self-emulsification time, cloud point, % transmittance and in vitro dissolution profiles. The optimized Liquid-SNEDDS (L-SNEDDS) with RHLB 13.76 gives globule size (82.8 nm), % T (96.7 %), in vitro release of AST (98.4 %) and LUM (97.07%) at 45 min. was converted into S-SNEDDS by using neusilin US2 as an adsorbent. The S-SNEDDS was characterized by SEM, globule size (98.24 nm), % T (95.02 %), in vitro release of ART (95.18 %) and LUM (96.4%) at 45 min. DSC and FTIR study for S-SNEDDS assure that there was an absence of any chemical interaction within the drug and carrier. SEM, X-ray diffraction studies confirmed that drugs exist in amorphous nature. The present research successfully developed S-SNEDDS for bioavailability enhancement of AST and LUM in fix dose combination&#x0D;

Validation of RP-HPLC Method for Determination of Omeprazole in Dissolution Media and Application to Study in-vitro Release from Solid- SNEDDS

Background: Omeprazole has poor water solubility, is unstable in acidic solutions, and undergoes first pass metabolism which results in lowering its bioavailability. A solid Self-Nano Emulsifying Drug Delivery System (SNEDDS) was previously prepared to enhance its dissolution. Objective: Development and validation of a RP-HPLC method with UV detection for the determination of omeprazole in 0.1N HCl and in 0.01 M phosphate buffer (pH 7.4). Methods: Validation was according to the ICH Q2 (R1) guidelines in terms of linearity, accuracy and precision, lower limit of quantification, sensitivity, specificity, and robustness. The developed and validated method was used to study the in-vitro dissolution of the drug from the solid-SNEDDS, commercial products and of the unprocessed drug. The dissolution was studied in 500 ml of 0.1N HCl during the first 2 hours, and 900 mL of 0.01 M phosphate buffer (pH 7.4) during the last hour (37 ± 0.5 oC and 100 rpm). Results: The method was linear in the range 1-50 μg/ml, accurate and precise as indicated by the ANOVA test. It was specific to the drug and the pharmaceutical excipients did not affect the determination of its concentration. The method was robust to small changes in pH, composition, and flow rate of the mobile phase. The dissolution rate of omeprazole from the Solid-SNEDDS was faster than that from two commercial dosage forms and than the dissolution rate of the unprocessed drug. Conclusion: The method met the acceptance criteria and was applied successfully in studying the rate of dissolution of the drug.

Comparative Bioavailability Study of Solid Self-Nanoemulsifying Drug Delivery System of Fenofibric Acid in Healthy Male Subjects

Objective: This study aimed to evaluate the effect of solid self-nanoemulsifying drug delivery system (S-SNEDDS) formation on the bioavailability of fenofibric acid. Subject and Methods: Three formulations of fenofibric acid, namely, S-SNEDDS containing medium-chain triglyceride (FS1), S-SNEDDS containing long-chain triglyceride (FS2), and FSt as tablet of innovator product, were used in this study. Bioavailability study was conducted in 12 Indonesian healthy male subjects after a single-dose administration of each formulation with three-way crossover design. Blood samples were collected from 0 to 72 h after drug administration and then analyzed using the high-performance liquid chromatography method. Data were statistically analyzed using the ANOVA and the Wilcoxon signed-rank test using a p value of 0.05. Dissolution test was carried out with USP dissolution apparatus using three medium (pH 1.2, 4.5 and 6.8). Results: The rates of absorption of fenofibric acid from S-SNEDDS FS1 and FS2 were significantly increased about 1.78 and 2.40 times, respectively, relative to FSt. T_max values of FS1 and FS2 were shorter than FSt, namely, 0.96 ± 0.438 h (FS1), 0.71 ± 0.445 h (FS2), and 1.71 ± 0.840 h (FSt), respectively. Meanwhile, the C_max and AUC values of FS1, FS2, and FSt were found to be not significantly different with a p value of >0.05. S-SNEDDS formation increased the dissolution rate in acid medium. Conclusions: S-SNEDDS increased the dissolution rate in acid medium and absorption rate of fenofibric acid but did not increase the extent of fenofibric acid absorption.

SOLID SELF NANO EMULSIFYING DRUG DELIVERY SYSTEM OF FENOFIBRIC ACID: PHYSICOCHEMICAL PROPERTIES AND IN VITRO EVALUATION

Physicochemical properties and dissolution of Fenofibric acid (FA) solid self-nano emulsifying drug delivery system (solid SNEDDS) were investigated. Kollisolv® MCT 70 (medium-chain triglyceride), Kolliphor® RH 40, and Transcutol® HP as the oil, surfactant, and cosurfactant for SNEDDS formulation. The optimized SNEDDS formulation was solidified into solid SNEDDS using porous carriers (Neusilin® US2 and Aerosil 200), with a ratio of 33% and 50% (w/v) respectively (SS1–SS4). The selected solid SNEDDS formulation of FA (SS1) could increase the dissolution of FA 1.75-fold compared to the pure drug.

FORMULATION AND CHARACTERIZATION OF Γ-ORYZANOL LOADED SOLID SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEMS (S-SNEDDS)

In recent years, much attention has been paid to solid self-nanoemulsifying drug delivery systems (S-SNEDDS), which have shown reasonable successes in improving oral bioavailability of poorly soluble drugs. This drug delivery system combines the advantages of liquid SNEDDS with those of a solid dosage form and overcomes the limitations associated with liquid formulations. One optimized SNEDDS formulae F-5 were selected to be solidified by spray drying technique using Aerosil 200 as solid carrier. Characterization of GOZ Loaded S-SNEDDS by angle of repose of the one S-SNEDDS formulae F-5 were 24.12°± 1.10°, these values indicate that all formulae have good flow ability. The bulk density of the two formulae F-5 was found to be 0.47 ± 0.03 g/mL. However, tapped density was 0.57±0.02 g/mL for formula F-5. Carr’s index of formulae F-5 was found to be 13.57±1.09 which give an indication about the good flowability of the one S-SNEDDS formulae. The efficiency of self-emulsification can also be estimated by measuring the emulsification time. The emulsification time was 41.57±1.12 s. for formula F-5. The small values of PDI shown by S-SNEDDS formulae F-5 (0.403±1.12) indicate homogenous droplet population and narrow globule size distribution. The thermo gram of pure GOZ exhibited a sharp endothermic peak at about 137.25°C, corresponding to its melting point. The drug loading efficiency was found to be 96.23±0.65 for formula F-5. Within the initial one hour of the in vitro release study, only 41.02%±1.23% of GOZ was dissolved from pure drug and marketed tablets, whereas the S-SNEDDS formulae showed improved release within the same time period. GOZ dissolved and released from S-SNEDDS reached 90.02%±1.02% for formula F-5, within one hour.