Enhancement Of Oral Bioavailability Research Articles

Combination of Phospholipid Complex and Matrix Dispersion.

Phospholipid complexation, despite being a successful, versatile, and burgeoning strategy, stickiness of phospholipids leads to suboptimal dissolution rate of drugs. This work was undertaken to fabricate simvastatin-phospholipid complex (SIM-PLC)-loaded matrix dispersion (SIM-PLC-MD) using Soluplus® as carrier material, to augment dispersibility and dissolution of SIM-PLC without altering complexation between simvastatin (SIM) and phospholipid. SIM-PLC and SIM-PLC-MD were prepared using solvent evaporation and discontinuous solvent evaporation techniques, respectively. The successful complexation was substantiated by FTIR method. Besides, PXRD and SEM studies disclosed the absence of crystallinity of SIM in both SIM-PLC and SIM-PLC-MD. The TEM analysis monitored the self-assembly of SIM-PLC and SIM-PLC-MD into colloidal structures, which could be correlated with redispersion in GIT fluids upon oral administration. The considerable increase in hydrophilicity of SIM-PLC-MD and SIM-PLC as evident from partition coefficient experiment can further be correlated with their remarkably improved solubility profiles in the following pattern: SIM-PLC-MD˃SIM-PLC˃SIM. Correspondingly, improved dispersibility of SIM-PLC-MD in comparison to SIM-PLC can be accountable for accelerated dissolution rate by 2.53-fold and 1.5-fold in pH 1.2 and 6.8 conditions, respectively. The oral pharmacokinetic evaluation in Sprague Dawley (SD) rats revealed 3.19-fold enhancement in oral bioavailability of SIM through SIM-PLC-MD when compared with plain SIM, whereas 1.83-fold increment was observed in the case of SIM-PLC. Finally, the efficacy experimentation in SD rats revealed that SIM-PLC-MD significantly reduced triglycerides and cholesterol levels in comparison to SIM and SIM-PLC. These outcomes suggest that a matrix dispersion strategy improves oral bioavailability and hypolipidemic activity of SIM.

Preparation, Characterization and Optimization of Irbesartan Loaded Solid Lipid Nanoparticles for Oral Delivery

The purpose of this study was to develop and evaluate irbesartan (IS) loaded solid lipid nanoparticles (SLNs; IS-SLNs) that might enhance the oral bioavailability of IS. IS, an angiotensin-receptor antagonist, used to treat hypertension. However, poor aqueous solubility and poor oral bioavailability has limited therapeutic applications of IS. Components of the SLNs include either of trimyristin/tripalmitin/tristearin/trilaurate/stearic acid/beeswax, and surfactants (Poloxamer 188 and soylecithin). The IS-SLNs were prepared by hot homogenization followed by ultrasonication method and evaluated for particle size, poly dispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE), drug content and in vitro drug release. The physical stability of optimized formulation was studied at refrigerated and room temperature for two months. The optimized IS-SLN formulation (F4) had a mean diameter of about 217.6±3.62 nm, PDI of 0.163±0.032, ZP of -28.5±4.12, assay of 99.8±0.51 and EE of 93.68±2.47%. The formulation showed sustained drug release compared with control formulation over 24 h. Optimized formulation was found to be stable over two months. IS-SLN showed nearly spherical in shape using and converted to amorphous form by DSC. Thus, the results conclusively demonstrated SLNs could be considered as an alternative delivery system for the oral bioavailability enhancement of IS.

A Review on Novel vesicular systems for enhanced Oral bioavailability of Lipophilic drugs

The poor oral bioavailability of many drugs is mainly due to the poor aqueous solubility, chemical instability and pre-absorptive metabolism. Numerous approaches have been developed for enhancement of oral bioavailability and were currently in the clinical application. Even though, some drugs not meet the required clinical application due to the patient compliance and ineffective therapeutic levels. Vesicular delivery systems are considered as alternative delivery for the enhancement the bioavailability of this category of drugs. The enhanced bioavailability of the liphophilic drugs from the vesicular systems mainly due to the increased effective surface area of the drug in the presence of lipids, surfactants and co surfactants, enhanced lymphatic uptake, altered gastric motility and by virtue of their small particle size. Extensive literature is available for the properties, applications, and preparation and evaluation methods. This review mainly dealt with the reported drug loaded various vesicular systems such as liposomes, niosomes, lipid nanoparticles, self-emulsifying delivery system, nanosuspensions.

Design and Development of Sustained Release Vildagliptin-Loaded Silica Nanoparticles for Enhancing Oral Bioavailability

Design and Development of Sustained Release Vildagliptin-Loaded Silica Nanoparticles for Enhancing Oral Bioavailability

Enhancement of oral bioavailability and anti-hyperuricemic activity of aloe emodin via novel Soluplus®-glycyrrhizic acid mixed micelle system.

The objective of this study was to fabricate a novel drug delivery system using Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) and glycyrrhizic acid to improve solubility, bioavailability, and anti-hyperuricemic activity of aloe emodin (AE). The AE-loaded mixed micelles (AE-M) were prepared by thin-film hydration method. The optimal AE-M contained small-sized (30.13 ± 1.34nm) particles with high encapsulation efficiency (m/m, %) of 90.3 ± 1.08%. The release rate of AE increased in the micellar formulation than that of free AE in the four media (DDW, pH 7.0; phosphate buffer solution, pH 7.4; phosphate buffer solution, pH 6.8; and hydrochloric acid aqueous solution, pH 1.2). In comparison to free AE, the pharmacokinetic study of AE-M showed that its relative oral bioavailability increased by 3.09 times, indicating that mixed micelles may promote gastrointestinal absorption. More importantly, AE-M effectively reduced uric acid level by inhibiting xanthine oxidase (XOD) activity in model rats. The degree of ankle swelling, serum levels of interleukin (IL)-1, and IL-6-related inflammatory factors levels all decreased in the gouty arthritis model established via monosodium urate (MSU) crystals. Taken together, the AE-M demonstrated the potential to improve the bioavailability, anti-hyperuricemic activity, and anti-inflammation of AE.

Facile preparation of solid dispersions by dissolving drugs in N-vinyl-2-pyrrolidone and photopolymerization

Drug solid dispersions improve the dissolution of drugs in aqueous media for enhancement of oral bioavailability. The current preparation methods of drug solid dispersions mainly involve the evaporation of solvents or the melting of drugs and matrix. Here, we create a new and simple method for the preparation of drug solid dispersions by dissolving drugs in N-vinyl-2-pyrrolidone (NVP) and then NVP photopolymerization. A variety of drugs were explored to find whether they were suitable for this method and only some of them were soluble in NVP and formed transparent and hard solid dispersions, including fluconazole, ketoconazole, bifonazole, miconazole nitrate, sulfamethoxazole, aspirin, ibuprofen and artesunate. The formation of photocuring solid dispersions was highly related to the free radical scavenging function of drugs. Those drugs with strong free radical scavenging capability, including curcumin, resveratrol, quercetin, genistein, puerarin, nicergoline, olanzapine, indomethacin, did not form solid dispersions. They scavenged 2,2-diphenyl-1-picrylhydrazyl free radicals, which was demonstrated by ultraviolet spectrometry and electron spin resonance. The scavenging of free radicals stopped the chain polymerization of NVP. The Fourier transform infrared spectra, X-ray diffraction and differential scanning calorimetry of ibuprofen solid dispersions and artesunate solid dispersions showed the molecularly miscible state of the drugs and the hydrogen bonding between the drugs and polyvinyl pyrrolidone. The NVP-based solid dispersions of the two drugs had faster and more complete dissolution than their traditional solid dispersions. The NVP photopolymerization-based solid dispersion method provides a new choice for the production of solid dispersions in the research and industrial fields.

Development and Characterization of Venetoclax Nanocrystals for Oral Bioavailability Enhancement.

Venetoclax (VX) used in the treatment of chronic lymphocytic leukemia possesses low oral bioavailability (5.4%) and undergoes first-pass metabolism. Development of a formulation to overcome its bioavailability problem can be done by using nanocrystals which has many scientific applications. Nanocrystals of VX were formulated using amalgamation of precipitation and high-pressure homogenization method, in which polyvinyl alcohol (PVA) was selected as stabilizer. Process parameters like concentration of stabilizer, homogenization pressure, number of homogenization cycle, and concentration of lyoprotectant were optimized to obtain the desired particle size for the preparation of nanocrystal formulation. HPLC methods were developed and validated in-house for determination of in vitro dissolution data and in vivo bioavailability data. Physicochemical characterization was done to determine the particle size (zeta sizer), crystalline nature (DSC and XRPD), solubility (shaker bath), and dissolution (USP type 2 apparatus). Lyophilized VX nanocrystals of size less than 350 nm showed substantial increase in saturation solubility (~20 folds) and dissolution in comparison with free VX. In vitro release study revealed that 100% dissolution was achieved in 120 min as compared to VX free base which is having less than 43.5% dissolution in 120 min. Formulations of VX remain stable for 6 months under accelerated stability conditions. In vivo pharmacokinetic data in male Sprague-Dawley rats showed (~2.02 folds) significant increase in oral bioavailability of VX formulation as compared to free drug because of rapid dissolution and absorption which makes the nanocrystal formulation a better approach for oral administration of poorly soluble drugs.

The contribution of absorption of integral nanocrystals to enhancement of oral bioavailability of quercetin

In this study, self-discriminating hybrid nanocrystals was utilized to explore the biological fate of quercetin hybrid nanocrystals (QT-HNCs) with diameter around 280 nm (QT-HNCs-280) and 550 nm (QT-HNCs-550) following oral and intravenous administration and the contribution of integral nanocrystals to oral bioavailability enhancement of QT was estimated by comparing the absolute exposure of integral QT-HNCs and total QT in the liver. Results showed that QT-HNCs could reside in vivo as intact nanocrystals for as long as 48 h following oral and intravenous administration. A higher accumulation of integral QT-HNCs in liver and lung was observed for both oral and intravenous administration of QT-HNCs. The particle size affects the absorption and biodistribution of integral QT-HNCs and total QT. As compared to QT-HNCs-550, QT-HNCs-280 with smaller particle size is more easily absorbed, but dissolves faster in vivo, leading to higher distribution of QT (146.90 vs. 117.91 h·μg/mL) but lower accumulation of integral nanocrystals (6.8 2e10 vs. 15.27e10 h·[p/s]/[µW/cm²]) in liver following oral administration. Due to its slower dissolution and enhanced recognition by RES, QT-HNCs-550 with larger diameter shows higher liver distribution for both of QT (1015.80 h·μg/mL) and integral nanocrystals (259.63e10 h·[p/s]/[µW/cm²]) than those of QT-HNCs-280 (673.82 & 77.66e10 h·[p/s]/[µW/cm²]) following intravenous administration. The absolute exposure of integral QT-HNCs in liver following oral administration of QT-HNCs are 8.78% for QT-HNCs-280 and 5.88% for QT-HNCs-550, while the absolute exposure of total QT for QT-HNCs-280 and QT-HNCs-550 are 21.80% and 11.61%, respectively. Owing to imprecise quantification method, a surprisingly high contribution of integral QT-HNCs to oral bioavailability enhancement of QT (40.27% for QT-HNCs-280 and 50.65% for QT-HNCs-550) was obtained. These results revealed significant difference in absorption and biodistrbution between integral nanocrystals and overall drugs following oral and intravenous administration of QT-HNCs, and provided a meaningful reference for the contribution of integral nanocrystals to overall bioavailability enhancement.

Liquid Crystalline Phases for Enhancement of Oral Bioavailability.

Liquid crystalline phases (LCPs) are generated upon lipolysis of ingested lipids in the gastrointestinal tract. The breaking off and subsequent evolution of LCPs produce more advanced vesicular and micellar structures which facilitate oral absorption of lipids, as well as co-loaded drug entities. Owing to sustained or controlled drug release, bioadhesiveness, and capability of loading drugs of different properties, LCPs are promising vehicles to implement for enhancement of oral bioavailability. This review aims to provide an overview on the classification, preparation and characterization, in vivo generation and transformation, absorption mechanisms, and encouraging applications of LCPs in enhancement of oral bioavailability. In addition, we comment on the merits of LCPs as oral drug delivery carriers, as well as solutions to industrialization utilizing liquid crystalline precursor and preconcentrate formulations.

Use of combined nanocarrier system based on chitosan nanoparticles and phospholipids complex for improved delivery of ferulic acid

A novel nanocarrier system of phospholipids complex loaded chitosan nanoparticles (FAPLC CNPs) was developed to improve the oral bioavailability and antioxidant potential of FA. FAPLC CNPs were optimized using a Box-Behnken Design (BBD). FAPLC CNPs were characterized using differential scanning calorimetry, Fourier transforms infrared spectroscopy, powder x-ray diffractometry, proton nuclear magnetic resonance, solubility, in vitro dissolution, ex vivo permeation, and in vivo antioxidant activity in carbon tetrachloride (CCl4)-induced albino rat model. The characterization studies indicated a formation of the complex as well as FAPLC CNPs. The FAPLC CNPs exhibited a lower particle size ~123.27 nm, PDI value ~0.31, and positive zeta potential ~32 mV respectively. Functional characterization studies revealed a significant improvement in the aqueous solubility, dissolution, and permeation rate of FAPLC and FAPLC CNPs compared to FA and FA CNPs. The FAPLC CNPs showed significant enhancement of in vivo antioxidant activity of FA by restoring the elevated marker enzymes in the CCl4-intoxicated rat model compared to FA CNPs. Moreover, the pharmacokinetic analysis demonstrated a significant enhancement of oral bioavailability of FA from FAPLC CNPs compared to FA CNPs. These findings show that FAPLC CNPs could be used as an effective nanocarrier for improving the oral delivery of FA.

A self-assembled amphiphilic polysaccharide-based co-delivery system for egg white derived peptides and curcumin with oral bioavailability enhancement.

Egg white derived peptides (EWDP) and curcumin are well known for diverse biological activities, but the combinational usage of the two natural nutraceuticals is extremely limited by their low oral bioavailability and distinctly different polarities. Therefore, this study aimed to exploit a facile self-assembled amphiphilic system for oral co-delivery of hydrophilic egg white derived peptides (EWDP) and hydrophobic curcumin. The hydrophobic curcumin was first loaded into the hydrophobic cavity of β-cyclodextrin (β-CD) as a core. Then, the hydrophilic EWDP was absorbed into the region between the core and the N-[(2-hydroxy-3-trimethyl ammonium) propyl] chitosan (HTCC) shell to form the amphiphilic nanoparticles (NPs) via layer-by-layer self-assembly. The resulting NPs showed ideal oral applicability with excellent colloidal properties and encapsulation capacity for EWDP and curcumin at pH 2.0-7.0. X-ray Photoelectron Spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (1H NMR), X-ray diffraction (XRD) and differential scanning calorimetry (DSC) results indicated that hydrogen bonding and hydrophobic interaction were the main driving force for the formation of amphiphilic NPs. Upon combination with HTCC, EWDP (both shell material and core nutraceuticals) could facilitate curcumin loading into the deeper β-CD cavity site with admirable solubility improvement. Moreover, EWDP and curcumin after co-delivery exhibited superior bioavailability (especially for bioactivity and cellular absorption) than the simple mixture and conventional curcumin inclusion complex. Overall, these findings are enlightening for the rational peptide based oral co-delivery system formulations for a broader range of hydrophilic and hydrophobic nutraceuticals (initially synergistic or not) in the food and related health-promoting fields.

Enhancement of Aqueous Solubility and Oral Bioavailability of Bcs Class II Drug by Dry Emulsion

Liquid emulsions have distinct advantages over other dosage forms by improving oral bioavailability as well as by reducing the side effects. On contrary, liquid emulsion exhibit lack of physicochemical stability and compliance issues. To overcome these problems, dry emulsion formulation recommended. Dry emulsions are formulated by spray drying, evaporation and rotary evaporation. The aim of the present investigation is to improve the dissolution and oral bioavailability of poorly water soluble drug Olmesartan medoxomil by preparing dry emulsion. Olmesartan medoxomil is poorly soluble drug used for treatment of high blood pressure, showing absorption window at stomach and upper part of small intestine. Dry emulsion was ready by victimisation purgative during which drug is very soluble, using poloxamer188 as water soluble carrier and aerosil 200 as an adsorbent. The preferred oils were castor oil, olive oil, soybean oil and isopropyl myristate and polymers were PEG400, Eudragit EPO and Poloxamer 188. Dry emulsion was prepared by spray drying. Dry emulsion was evaluated for drug content, percentage moisture content, aqueous solubility, dissolution study and in-vivo bioavailability study. In vitro drug release of dry emulsion was studied by using USP type II paddle dissolution apparatus. The solubility of the drug was increased with surfactant and polymer at 1:1 ratio. Probable mechanisms of improved solubility were characterized by particle size determination, Differential Scanning Calorimetry (DSC), Powder X-ray Diffractometry (PXRD) and Scanning Electron Microscopy (SEM). This study revealed that solid dry emulsion technique could prove promising for improvement of solubility, dissolution rate and oral bioavailability of Olmesartan medoxomil.

Enhancement of oral bioavailability of quercetin by metabolic inhibitory nanosuspensions compared to conventional nanosuspensions

Quercetin-loaded nanosuspensions (Que-NSps) added metabolic inhibitors were evaluated as drug delivery system to promote the oral bioavailability of quercetin. Que-NSps were prepared respectively using d-alpha tocopherol acid polyethylene glycol succinate (TPGS) or Soybean Lecithin (SPC) as stabilizer. On the basis, Piperine (Pip) or sodium oleate (SO) was, respectively, encapsulated in Que-NSps as phase II metabolic inhibitors. The resulting Que-NSps all displayed a mean particle size of about 200 nm and drug loading content was in the range of 22.3–27.8%. The release of quercetin from Que-NSps was slow and sustained. After oral administration of 50 mg/kg different Que-NSps, the levels of free quercetin in plasma were significantly promoted, the concentration of quercetin metabolites (isorhamnetin and quercetin 3-O-β-d-Glucuronide) were decreased. The absolute bioavailability was, respectively 15.55%, 6.93%, 12.38%, and 23.58% for TPGS-Que-NSps, TPGS-SO-Que-NSps, SPC-Que-NSps, and SPC-Pip-Que-NSps, and 3.61% for quercetin water suspension. SPC-Pip-Que-NSps turned out to an ideal nanocarrier combined nano drug delivery system together with metabolic inhibitor to promote oral absorption of quercetin.

Quetiapine Fumarate Loaded Nanostructured Lipid Carrier for Enhancing Oral Bioavailability: Design, Development and Pharmacokinetic Assessment

Quetiapine Fumarate Loaded Nanostructured Lipid Carrier for Enhancing Oral Bioavailability: Design, Development and Pharmacokinetic Assessment

Quetiapine Fumarate Loaded Nanostructured Lipid Carrier for Enhancing Oral Bioavailability: Design, Development and Pharmacokinetic Assessment

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Solid lipid nanocarriers as alternative drug delivery system for improved oral delivery of drugs

Oral bioavailability of drugs is mainly limited due to the poor aqueous solubility, enhanced chemical degradation, reduced permeation and/or first pass metabolism. Various novel delivery systems are developed for improved oral bioavailability of these drugs such as modified orals, buccal, transdermal and osmotic delivery systems. Colloidal carrier systems such as nanoparticles, lipid nanoparticles, nanoemulsions, microspheres, liposomes, resealed erythrocytes and transfersomes were also developed to enhance the oral delivery. Among these, solid lipid nanocarriers (SLNs) also gain much attention on the enhancement of oral bioavailability. SLNs are submicron sized nanoparticles and composed of solid lipid, surfactants and cosurfactants. The enhanced oral bioavailability of poorly soluble drugs from SLNs might be due to the reduced particle size, bypassed presystemic metabolism, and enhanced gastric mucosa permeability. Vast literature is available for the advantages, limitations, preparation methods, evaluation parameters and application of SLNs in different routes. This review mainly focused on list of drugs developed as SLNs and considered as an alternative approach to enhance the oral bioavailability based on pharmacokinetic as well as pharmacodyanmic parameters was discussed.
 Keywords: Oral bioavailability, solubility, first-pass metabolism, solid lipid nanoparticles, pharmacokinetics, pharmacodynamics.

Novel Delivery System Used for Oral Bioavailability Enhancement of Poorly Water Soluble Drugs

Majority of the drugs used for the treatment of various diseases are administered by oral route using conventional delivery. The major drawback of the oral administration is the poor bioavailability due to the poor water solubility, chemical stability and pre-systemic metabolism. Numerous researches are going on for the improvement of oral bioavailability of drugs using novel drug delivery systems as an alternative to conventional delivery systems. Majority of the novel delivery system includes; solid dispersion, sustained, controlled buccal, gastro retentive, nano carrier delivery systems such as lipid nanoparticles, and self-emulsifying systems. The oral bioavailability improvement by these delivery systems might be due to the increased particle size, improved dissolution and/or permeation and subsequently bioavailability of the drugs. In this review, we attempt to discuss the various novel delivery systems developed for the enhancement of oral bioavailability of poorly water soluble therapeutics.
 Keywords: Oral bioavailability, poor solubility, stability, metabolism, novel delivery systems, nano carriers.

Enhancement of oral bioavailability of drugs using lipid-based carriers: a meta-analysis study

Cancer is the disease of this era. Its therapy is moving through ups and downs not only due to poor effectiveness of many treating drugs, but also due to the serious side effects always evolving. In an attempt to overcome this problem, many systems, including lipid-based carriers, have been exploited for their oral delivery. Throughout this study, the meta-analysis tool was used to combine data from different studies and extract evidences that lipid-based carriers enhance the oral bioavailability. Consequently, increasing the efficiency and the reduction in side effects of drugs would follow. Accordingly, the usual parameter to indicate the bioavailability; the area under effect curve (AUC) was used where the lipid carriers have proven their superiority over conventional formulations. Interestingly, by comparing microemulsion/self-microemulsifying system (SMEDDS) versus liposomes/pro-liposomes as subgroups of the meta-analysis study, insignificant differences were recorded between them.

Chitosan/heparin polyelectrolyte complexes as ion-paring approach to encapsulate heparin in orally administrable SLN: In vitro evaluation

Enhancing oral bioavailability of hydrophilic drugs by encapsulation in lipid-based nanocarriers, including Solid Lipid Nanoparticles (SLN), has been well documented. In this work, high molecular weight heparin was “insolubilized” by an “ion-paring” approach, forming Chitosan/Heparin Polyelectrolyte Complexes (PEC) to promote its encapsulation in SLN. Hybrid PEC-SLN, heparin-loaded SLN (H-SLN) as well as naked PEC were prepared and characterized regarding size, Z potential, morphology, drug loading and drug release. Physicochemical characterization of the nanoparticles was also performed by differential scanning calorimetry (DSC), and Fourier Transform Infra-Red (FTIR) analysis. FITC-labeled naked PEC along with Nile Red labeled PEC-SLN were assessed on CaCo-2 cells to study cytotoxicity as well as cell internalization ability by cytometric and confocal analysis. Transepithelial electrical resistance (TEER) was measured on NCM460 cell monolayers to evaluate whether chitosan may induce a modification of tight junctions’ integrity at epithelial level. Results showed that the minimum size of PEC (around 170 nm) was at pH 5.5 with a positive surface charge and after encapsulation in SLN produced hybrid PEC-SLN with a size of about 370 nm and a negative zeta potential. In comparison to both H-SLN and naked PEC, PEC-SLN were able to achieve a pH-controlled drug release and showed on CaCo-2 cells low toxicity and rapid internalization. Finally, TEER measurements highlighted that the hybrid nanocarriers were internalized without interference in the membrane resistance. Therefore, PEC-SLN could be considered valuable candidate for further in vivo investigations about the systemic bioavailability of oral heparin.

Development of Solid Self – Nanoemulsified Drug Delivery System Containing Rosuvastatin

This study aims to solidify the self-nanoemulsifying drug delivery system with rosuvastatin (SNEDDS Ros) for application in solid dosage forms. The liquid SNEDDS Ros system is solidified by granulation and spray drying methods. Solid SNEDDS Ros was evaluated on the drug content, the Carr index, nanoemulsification efficiency and several criteria of nanoemulsion, formed after emulsification of solid SNEDDS Ros, such as droplet size, polydispersion index (PDI), the drug proportion in the oil phase. The study results show that solid SNEDDS Ros, prepared by granulation method using Prosolv SMCC 90 as an adsorbent, had good flowability with the Carr index of about 15. The nanoemulsion, obtained after emulsification of the solid SNEDDS, had an average particle size of 15 nm, PDI less than 0.2, drug nanoemulsified efficiency of 94 % and drug proportion in the oil phase of 84%.
 Keywords
 Rosuvastatin, SNEDDS, Solid SNEDDS, solidification.
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