Self-microemulsifying Drug Delivery System Formulation Research Articles

Application of Box–Behnken design in the preparation and optimization of fenofibrate-loaded self-microemulsifying drug delivery system (SMEDDS)

This study was designed to optimize a fenofibrate-loaded self-microemulsifying drug delivery system (SMEDDS) by using a response surface methodology. Box–Behnken design (BBD) and its desirability function were used to optimize the SMEDDS. The independent factors were the amounts of Labrafil M 1944 CS, Labrasol, and Capryol PGMC and the dependent variables were droplet size, cumulative percentage of drug released in 30 min and equilibrium solubility of fenofibrate in SMEDDS. Various response surface graphs were used to understand the effects of each factor, and the desirability function was then adjusted to optimize SMEDDS formulation. The experimental values of optimized formulation were in close agreement with predicted values. Furthermore, in vivo pharmacokinetic study of the optimized formulation showed significant increase in relative oral bioavailability compared to that of the powder suspension. In conclusion, the BBD demonstrated its effectiveness in optimizing the SMEDDS formulation and in identifying the effects of formulation variables.

Nano scale self-emulsifying oil based carrier system for improved oral bioavailability of camptothecin derivative by P-Glycoprotein modulation

Irinotecan is a camptothecin derivative with low oral bioavailability due to active efflux by intestinal P-glycoprotein receptors. Hence, no oral formulation is marketed for Irinotecan till date. However, an optimized Self micro emulsifying drug delivery system (SMEDDS), formulated to produce nano range oil droplets by using P-gp modulator excipients can tackle the issue and elevate the systemic availability of Irinotecan. The present work focuses on the development of SMEDDS for Irinotecan and evaluation of its in vitro, ex vivo and in vivo potentials. The SMEDDS were developed using Capmul MCM-C8, Cremophor EL and Pluronic L-121 as oil, surfactant and co-surfactant respectively and has good oil carrying capacity (30%) with competence to produce nano-scale oil droplets (130±2.13nm) on spontaneous emulsification. A much deeper penetration to the intestine was observed with SMEDDS by using confocal laser scanning microscopy (CLSM). Flow-cytometric studies also revealed the greater uptake of fluorescent probe in Caco-2 cell-lines with the use of SMEDDS. Biochemical estimation of LDH from the intestinal tissues treated with SMEDDS and free drug suspension confirmed that the developed formulation is safe for use. Furthermore, the AUC0→t of Irinotecan from the optimized SMEDDS formulation was found to be 4 folds higher than that from Irinotecan suspension on oral administration. The optimized SMEDDS formulation was found to be capable of maintaining the sustained plasma drug level of Irinotecan with better bioavailability.

Design, characterization and in vitro evaluation of SMEDDS containing an anticancer peptide, linear LyP-1

LyP-1 (CGNKRTRGC) is a nine amino acid peptide that shows high specificity for tumor lymphatics. The aim of this study was to develop lipid-based formulations containing the linear form of LyP-1 for lymphatic targeting. Self-microemulsifying drug delivery systems (SMEDDS) were designed for the delivery of linear LyP-1 by itself and as a solid dispersion (SD). Formulations were characterized in terms of physical stability, pH, morphological properties, droplet size distribution and zeta potential. Thermodynamically stable microemulsions were obtained with an average droplet size around 20 nm and zeta potential near neutrality. Cytotoxicity studies of blank and peptide-containing SMEDDS were carried out on Caco-2 cell line. Bioactivity studies of peptide-containing formulations were carried out on MDA-MB-231 breast cancer cell line. It was shown that blank and peptide-containing SMEDDS formulations were not cytotoxic to Caco-2 cell line. However, formulations containing the peptide and peptide SD led to a significant decrease in cell viability on breast cancer cells. It could be concluded that the SMEDDS formulations containing the linear LyP-1 were successfully developed for the lymphatic targeting of solid tumors in vitro.

Pharmacokinetics of a self-microemulsifying drug delivery system of tacrolimus

This study evaluated the pharmacokinetics of tacrolimus (Tac) in a novel self-microemulsifying drug delivery system (SMEDDS) for improved oral administration. SMEDDS Tac consisted of ethyl oleate as the oily phase, Solutol HS 15 as the surfactant and glycofurol as the co-surfactant and contained 0.5mg/mL tacrolimus. Blood and tissue concentrations of tacrolimus from two study groups (oral application of SMEDDS Tac and Prograf®) were determined using ELISA technique following tacrolimus administration in rats. There was no difference between area under the whole blood concentration–time curve in the SEDDM Tac group and the Prograf® group. Maximum concentrations of the drug were three times higher (P<0.05) in the SEDDM Tac group accompanied by a 3-fold earlier peak time. Elimination half-life was significantly lower in the SEDDM Tac group. Application of SMEDDS Tac increased tissue accumulation. Already after 15min, Tac levels of small intestine, liver, kidney, spleen, heart and bone marrow were significantly higher in the SMEDDS Tac group than in the Prograf® group (P<0.05). However, the Tac concentration in the kidney was significantly lower in the SMEDDS Tac group. Formulation of SMEDDS did not affect blood-brain barrier function. The SMEDDS is a potentially useful method for a local delivery of Tac to target organs. The selection of the optimum SMEDDS Tac composition might have advantage as an alternative oral dosage form for Tac.

Oral delivery of oil-based formulation for a novel synthetic cationic peptide of GnRH (gonadotropin-releasing hormone) antagonist for prostate cancer treatment

LXT-101, a cationic peptide is a novel antagonist of gonadotropin-releasing hormone (GnRH) for prostate cancer treatment. However, effective delivery of peptide drugs into the body by the oral route remains a major challenge due to their origin properties with high molecular weights, strong polarity and low stability in the gastrointestinal (GI) tract. In this study, we have developed a novel oral delivery of oil-based formulation in which therapeutic peptide LXT-101 are solubilized in oils and with this solution as oil phase, an optimum formulation of self-microemulsifying drug delivery system (SMEDDS) was developed. The peptide stability with the SMEDDS formulation in artificial gastric and intestinal fluid was tested in vitro. On the other hand, the testosterone level and plasma concentration of LXT-101 in rats after oral administration of the SMEDDS formulation were investigated in vivo. The data in vitro indicated that LXT-101 in the SMEDDS formulation was stable over 8 h in artificial gastric and intestinal fluid. LXT-101 can be absorbed in vivo and suppression of testosterone maintained in castration level within 12 h can be achieved effectively after SMEDDS formulation administered orally at a dose of 3.5 mg/kg. The approach can provide a potential way for delivery peptides by oral.

Analysis of the enhanced oral bioavailability of fenofibrate lipid formulations in fasted humans using an in vitro–in silico–in vivo approach

Lipid-based formulations have established a significant role in the formulation of poorly soluble drugs for oral administration. In order to better understand their potential advantages over solid oral dosage forms, we studied the solubility and dissolution/precipitation characteristics of three self-microemulsifying drug delivery system (SMEDDS) formulations and one suspension of micronized fenofibrate in lipid excipients, for which pharmacokinetic studies had already been reported in the open literature. The in vitro dispersion/dissolution studies were carried out in biorelevant media using USP II apparatus. These were followed up by in silico simulations using STELLA® software, in which not only dispersion/dissolution, but also the precipitation and re-dissolution of fenofibrate was taken into account. While unformulated drug exhibited poor solubility (0.22μg/mL in FaSSGF and 4.31μg/mL in FaSSIF-V2(PO4)) and dissolved less than 2% in dissolution tests, the solubility of fenofibrate in the presence of the lipid excipients increased dramatically (e.g., to 65.44μg/mL in the presence of the Myritol 318/TPGS/Tween 80 SMEDDS) and there was an attendant increase in the dissolution (over 80% from capsules containing the Myritol 318/TPGS/Tween 80 SMEDDS and about 20% from the dispersion of fenofibrate in lipid excipients). For the four lipid-based fenofibrate formulations studied, combining in vitro data in biorelevant media with in silico simulation resulted in accurate prediction of the in vivo human plasma profiles. The point estimates of Cmax and AUC ratio calculated from the in silico and in vivo plasma profiles fell within the 0.8–1.25 range for the SMEDDS solution and capsule formulations, suggesting an accurate simulation of the in vivo profiles. This similarity was confirmed by calculation of the respective f2 factors. Sensitivity analysis of the simulation profiles revealed that the SMEDDS formulations had virtually removed any dependency of absorption on the dissolution rate in the small intestine, whereas for the dispersion in lipid excipients, this barrier remained. Such results pave the way to optimizing the performance of oral lipid-based formulations via an in vitro–in silico–in vivo approach.

Formulation and in vivo Evaluation of a Self-Microemulsifying Drug Delivery System of Dutasteride

This study aimed to develop an effective formulation to improve the solubility and oral absorption of dutasteride by using a self-microemulsifying drug delivery system (SMEDDS). We used the d-optimal mixture design as a tool for developing an optimized SMEDDS formulation with excellent physicochemical characteristics such as mean particle size of <100 nm and percentage of drug dissolved at 15 min, >80%. An optimized dutasteride-loaded SMEDDS formulation consisted of 39.80% CapryolTM 90, 25.90% Cremophor® EL, and 34.30% Transcutol® HP and showed an emulsion droplet size of about 35.3 nm. Approximately 90% of dutasteride from the SMEDDS dissolved at 10 min in dissolution media of pH 1.2 and 6.8. Furthermore, pharmacokinetic studies in rats indicated that compared to the raw drug, the optimized SMEDDS formulation significantly improved the oral absorption of dutasteride. Therefore, preliminary results from our study suggest that the dutasteride-loaded self-microemulsifying formulation has a great potential for clinical application.

Mixed lipid phase SMEDDS as an innovative approach to enhance resveratrol solubility

Context: Despite its promising therapeutic activities, clinical use of resveratrol (RSV) is compromised with unfavorable biopharmaceutical properties, namely low water solubility.Objective: This work deals with improving RSV solubility and release rate through its incorporation in innovative mixed lipid phase self-microemulsifying drug delivery systems (SMEDDS).Methods: (Pseudo)ternary diagrams were constructed for different oils and surfactant mixtures. Selected systems were further evaluated for RSV solubility, self-emulsification ability, accelerated stability, dynamic viscosity, compatibility with hard gelatin capsules and in vitro dissolution of RSV.Results: Lipid phase composed of diverse lipid species, castor oil (long-chained triglyceride) and Capmul MCM (mixture of medium chain mono and diglycerides) allowed formulation of mixed lipid SMEDDS with lower surfactants content (60% Cremophor EL/RH 40/RH 60). Mixed lipid phase SMEDDS showed best self-emulsifying ability with regard to self-emulsifying time as well as droplet size and monodispersity of microemulsions obtained upon SMEDDS dilution with aqueous phase. Overall, incorporation of RSV in SMEDDS resulted in improved solubility (over 23-fold) and dissolution rate compared to crystalline RSV. All SMEDDS formulations were adequately viscous for filling into hard gelatin capsules (>150 mPaċs for empty SMEDDS; >400 mPaċs for RSV-loaded SMEDDS) and no leaking was observed during three months of storage.Conclusion: The presented work indicates the promising potential of mixed lipid SMEDDS formulations for future development of SMEDDS with lower surfactant content and no added cosolvents for incorporation of RSV and other poorly soluble drugs.

Development of a self-microemulsifying drug delivery system to enhance oral bioavailability of β-elemene in rats

Our purpose was to develop a self-microemulsifying drug delivery system (SMEDDS) to enhance oral absorption of β-elemene and evaluate its oral bioavailability in rats. Pseudo-ternary phase diagrams were constructed to identify the efficient self-microemulsification region. SMEDDS formulations were further optimized by measurement of mean droplet size and emulsification time. The in vitro release profile of SMEDDS was determined in different aqueous media. The optimal formulation, which consisted of 10 % Miglyol 812, 41.7 % Cremophor EL, 8.3 % Labrasol, 20 % Transcutol P and 200 mg/g β-elemene, demonstrated a higher release rate in simulated gastric fluid than emulsion and pure drug. In vivo studies showed that the relative bioavailability in rats of SMEDDS versus emulsion was 161.35 %. The C max for SMEDDS was also significantly higher than that of emulsion (P

Development and characterisation of a self-microemulsifying drug delivery systems (SMEDDSs) for the vaginal administration of the antiretroviral UC-781

UC-781 is highly selective and potent against HIV-1. However, its hydrophobic nature (logP 5.1) and lack of aqueous solubility have limited its development as a HIV microbicide. Self-microemulsifying drug delivery systems (SMEDDSs) have been developed to enhance the water solubility and bioavailability of hydrophobic drugs, such as UC781. In this study, we show the development of UC781-loaded SMEDDS and their enhanced release of UC781 from hard gelatine capsules, when compared to UC781 powder only. The majority of antiretrovirals being evaluated as potential HIV microbicides are hydrophobic. Therefore, a SMEDDS formulation offers an alternative approach to enhancing the vaginal absorption of these microbicidal candidates.

Combination of β-cyclodextrin inclusion complex and self-microemulsifying drug delivery system for photostability and enhanced oral bioavailability of methotrexate: novel technique

In the present study, we prepared an inclusion complex of methotrexate (MTX) with β-cyclodextrin (β-CD) in order to decrease its photosensitivity and enhance its aqueous solubility. Then we incorporated this inclusion complex in a self-microemulsifying drug delivery system (SMEDDS) overall to increase its oral bioavailability. The inclusion complex has been prepared by freeze drying method and characterized by differential scanning calorimetry (DSC), ultraviolet (UV), and infrared (IR) spectroscopy assays. The proper molecular ratio of MTX/β-CD was found to be of 1:7, and the water-solubility of MTX was increased in an average of 10-fold. The photostability studies showed that the MTX became stable on exposure to light. Construction of pseudoternary diagrams were investigated to prepare a MTX/β-CD inclusion complex loaded SMEDDS which was characterized by measuring the particle size and the zeta-potential. The optimum formulation of SMEDDS was a system consisting of ethyl oleate, tween 80, and propylene glycol with a mean droplet size of 39.42 nm. In vitro drug release in different pH media showed that the release profile of MTX from the MTX/β-CD loaded SMEDDS was influenced by the pH of the release medium and presented the characteristics of a sustained release profile. Finally, in-vivo studies showed an enhancement of the bioavailability of MTX from the MTX/β-CD loaded SMEDDS form of 1.57-fold. We concluded that the β-CD inclusion complex loaded SMEDDS improved the chemical and physiological properties of MTX and could be a promising means for the delivery of MTX and other unstable and lipophilic drugs by oral route.

Preparation and evaluation of self-microemulsifying drug delivery system of baicalein

The main object of this work is to prepare self-microemulsifying drug delivery system (SMEDDS) for oral bioavailability enhancement of a poorly water-soluble drug, baicalein. SMEDDS is the mixture of surfactants, cosurfactants, and oils, which are emulsified in aqueous media under conditions of gentle agitation or gastrointestinal motility. Solubility of baicalein was determined in various vehicles. Pseudo-ternary phase diagrams were constructed to identify the efficient self-emulsification region and droplet size distributions of the resultant microemulsions were determined using a particle size analyzer. Optimized SMEDDS formulations for baicalein were Cremophor RH40 (53.57%) as surfactant, Transcutol P (21.43%) as cosurfactant, and Caprylic capric triglyceride (ODO, 25%) as oil. The drug release rate of SMEDDS was significantly higher than that of the baicalein suspension. Comparison of the pharmacokinetics between baicalein-loaded SMEDDS and baicalein suspension was also performed in rats. The plasma concentrations of baicalein and baicalin, its mainly conjugated metabolite, were determined by HPLC method. The in vivo results showed that the absorption of baicalein from SMEDDS resulted in about 200.7% increase in relative bioavailability compared with that of the baicalein suspension. Our studies illustrated the potential use of SMEDDS for the delivery of hydrophobic compounds, such as baicalein by the oral route.

Application of Langmuir–Blodgett film technology on studying the formulation of self-microemulsifying drug delivery system (SMEDDS)

The polarity of oleic acid, medium-chain triglyceride and their mixtures with different ratios was determined by LB film technology. Then the particle diameter after emulsifying in water when these different oils were mixed with Cremophor EL-35 respectively was assayed. Then three formulations of SMEDDS using different oils were prepared. And their surface pressure-area isotherm curves and Gibbs change (ΔG) were investigated. The results showed that flexibility of LB film was much better when oil with lower polarity was used to prepare the SMEDDS. And this group of SMEDDS which has low Gibbs change (ΔG) was more stable with appropriate composition of oil, surfactant and co-surfactant. It can be concluded that LB film technology could be applied on the preliminary formulation study of SMEDDS. Our study may provide some theoretical basis and methods of formulation selection of SMEDDS.

Design and evaluation of a self-microemulsifying drug delivery system for apigenin

Objective of this study was to prepare, characterize and evaluate a self-microemulsifying drug delivery system (SMEDDS) with the aim to improve the solubility and dissolution of apigenin. Ternary phase diagrams were constructed in order to obtain the most efficient self-emulsification region, and the formulation of apigenin loaded SMEDDS was optimized by a simplex lattice experiment design. The optimal formulation of SMEDDS obtained was comprised of 60% Cremophor®EL, 30% Transcutol®HP and 10% Capryol™ 90. The equilibrium solubility of apigenin in SMEDDS was about 15 mg/g, and it could increase the solubility of apigenin in water for about 7500 folds. Apigenin loaded SMEDDS could turn into microemulsion when diluted with distilled water and the droplets were spherical under transmission electron microscope (TEM), the average particle size was 17.1 nm and zeta potential −5.18 mV. In vitro dissolution studies showed about 95% of apigenin was released within 10 min. All of the results showed that SMEDDS could enhance the solubility and dissolution of apigenin, and would be a potential carrier to improve the oral absorption of apigenin, a poorly water soluble drug.

Development of self-microemulsifying drug delivery system for oral bioavailability enhancement of berberine hydrochloride

The purpose of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) to improve the oral bioavailability of Berberine hydrochloride (BBH), an important bioactive compound from Chinese Medicines with poor water solubility. Pseudoternary phase diagrams were constructed using oil, surfactant and co-surfactant types to identify the efficient self-microemulsification region. SMEDDS was characterized by morphological observation, droplet size, zeta-potential determination, stability, in vitro release and in vivo bioavailability study. The optimal formulation with the best self-microemulsifying and solubilization ability consisted of 40% (w/w) of ethyl linoleate and oleic acid (2:1), 35% (w/w) Tween-80 and 25% (w/w) glycerol. The SMEDDS of BBH could exhibit good stability. In vitro release test showed a complete release of BBH from SMEDDS was in 5 h. In vivo results indicated that the peak plasma concentration (Cmax) and the area under the curve (AUC0→12 h) of SMEDDS of BBH were higher than the commercial tablet by 163.4% and 154.2%, respectively. The relative bioavailability of SMEDDS of BBH was enhanced about 2.42-fold compared with the commercial tablet in rats. The study confirmed that the SMEDDS formulation could be used as a possible alternative to traditional oral formulations of BBH to improve its bioavailability.

Characterisation and evaluation of self-microemulsifying drug delivery system of Brucea javanica oil

A self-microemulsifying drug delivery system (SMEDDS) of Brucea javanica oil (BJO) was developed and evaluated for its oral absorption and bioavailability. Based on a solubility study and pseudo-ternary phase diagrams, the self-microemulsifying formulation composed of BJO, Cremorphor RH40, Plurol Oleique CC 497 and glycerol (30/42/20/8, % w/w) was prepared and characterised, including particle size, morphology, in vitro cytotoxicity and in vivo anti-tumour effects. The mean diameter of the final formulation was 41.5±3.5 nm. The BJO-loaded SMEDDS (BJOS) and the control preparation of BJO were administered orally to beagle dogs for pharmacokinetics and bioavailability studies. Oleic acid, which was considered as the main active and indicative component in BJO, was determined by gas chromatography. The cytotoxicity and anti-tumour effects of BJOS were evaluated in SMMC-7721 and BGC-823 cancer cell lines and sarcoma 180-bearing mice. The data showed that the oral relative bioavailability of commercial emulsion of BJO (BJOE) was 2.3-fold higher than that of BJO. Moreover, the IC50 value of BJOS group was nearly one-fourth compared to that of commercial BJOE. BJOS could significantly inhibit tumour growth via intra-gastric administration. The Letter illustrates that the developed SMEDDS formulation possessed great potential to be an alternative for traditional oral formulations of BJO.

Design, development and optimization of selfmicroemulsifying drug delivery system of an anti-obesity drug

The aim of the present work was to formulate a self-microemulsifying drug delivery system (SMEDDS) containing orlistat. The oil, surfactant and co-surfactant were decided based on the solubility studies. Pseudoternary phase diagrams were plotted, microemulsification area was determined and different formulations were prepared. Particle size, zeta potential, dispersibility test and thermodynamic stability studies were measured. In-vitro dissolution test of thermodynamically stable formulations OS-B and OS-C were carried and results were compared with those of plain drug and suspension formulation. Stability studies performed indicated that formulation OS-C remained stable over 12 months period. Thus this investigation concluded that hydrophobic drugs like orlistat can be delivered effectively through the formulation of SMEDDS.

Formulation and Evaluation of Self microemulsifying drug delivery system of low solubility drug for enhanced solubility and dissolution

Atorvastatin is a BCS class II lipid lowering agent. It is insoluble in aqueous solution of pH 4 and below; it is very slightly soluble in water and pH 7.4 phosphate buffer. In the present investigation an attempt has been made to enhance solubility and dissolution of poorly soluble drug by formulating self microemulsifying drug delivery system (SMEDDS). The solubility of atorvastatin in individual microemulsion components viz. oil and surfactants was determined. The surfactants were screened for emulsification ability. Based on the solubility determinations and emulsification properties sunflower oil and surfactants cremophor RH 40 and capmul MCM C8 were selected for further study. The solubility of atorvastatin in different ratios of selected oil and surfactants was determined. The composition of oil:surfactants with maximum solubility for atorvastatin was used for SMEDDS formulation. Pseudoternary phase diagrams were used to evaluate the microemulsification existence area. Formulation development and screening was done based on results obtained from phase diagrams and characteristics of resultant microemulsions. The microemulsions were evaluated for emulsion droplet size, self emulsification and phase separation, In vitro dissolution and stability. The SMEDDS formulation showed complete release in 30 min. as compared with the plain drug, which showed a limited dissolution rate.

Cinnarizine loaded lipid based system: preparation, optimization and in-vitro evaluation

Background and Aim: Cinnarizine (CNZ) a piperazine derivative with anti-histaminic activity and high affinity to H1 receptors is currently used for the treatment of cerebral arteriosclerosis, cerebral thrombosis, and subarachnoid hemorrhage. The aim of present investigation was to develop a lipid based system i.e. selfmicroemulsifying drug delivery system (SMEDDS) to enhance the oral bioavailability of poorly water soluble CNZ. Materials and Methods: The solubility of CNZ in various oils was determined to identify the oil phase for the preparation of SMEDDS. Various surfactants and co-surfactants were screened for their ability to emulsify the selected oil. A Pseudo-ternary phase diagrams were constructed at ambient temperature to identify the efficient self-microemulsifying region using a water titration method. The prepared formulations of SMEDDS were evaluated for their Robustness to dilution, emulsification time, drug loading efficiency, phase separation, droplet size, zeta potential, TEM etc. Result: The optimized SMEDDS formulation contained CNZ (25mg), Oleic acid (16.66%w/w), Tween 80 (55.55%w/w), Transcutol P (27.77%w/w). The optimized formulation of the CNZ loaded SMEDDS exhibited a complete in vitro release in 5min as compared with marketed formulation which had a limited dissolution rate. Conclusion: These results suggest the potential use of SMEDDS to improve the dissolution and hence oral bioavailability of poorly water soluble CNZ. Keywords––Bioavailability, Cinnarizine, Entrapment efficiency, Pseudoternary phase diagram, Selfmicroemulsifying drug delivery system etc.

Development and characterization of liquid and solid self-microemulsifying drug delivery system of Tacrolimus

Tacrolimus is an immunosuppressant agent for the prevention and treatment of graft rejection in solid organ transplantation patients. Tacrolimus is a poorly water-soluble drug. Its absorption is further limited due to the involvement of an efflux transporter P-glycoprotein and metabolism via cytochrome P450. The objective of presentinvestigation was to develop and characterize a liquid self-microemulsifying drug delivery system (SMEDDS) and a solid SMEDDS by using bioenhancer excipients like Tween 20 and Tween 80, which are known for their inhibiting action on CYP 450 and P-glycoprotein efflux pump. Solubility of Tacrolimus was determined in various vehicles, including oils, surfactants and cosolvents. Pseudoternary phase diagrams were constructed to identify the most efficient self-emulsification region. The optimized formulations were characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD) and globule size analysis. The optimized liquid SMEDDS formulation contained 20% Phosal 53 MCT as oil, 60% Tween 20 as surfactant and 20% ethanol as cosolvent. Liquid SMEDDS was converted to solid SMEDDS by using Aerosil-200 and Florite-RE as inert solid adsorbents. The optimized liquid and solid SMEDDS showed higher drug release than the marketed capsule and pure API powder. For optimized liquid SMEDDS and solid SMEDDS, the globule sizes were found to be 140.9 nm and 304.6 nm, respectively. DSC and XRD results of solid SMEDDS confirmed that the drug present in the formulation was in an amorphous state. Shelf-lives for liquid SMEDDS and solid SMEDDS were found to be 1.76 and 2.27 years, respectively. The prepared liquid SMEDDS and solid SMEDDS containing bioenhancer excipients increase the in vitro dissolution rate of lipophilic Tacrolimus.