Liquid Self-microemulsifying Drug Delivery System Research Articles

Effects of Hydrophilic Carriers on Structural Transitions and In Vitro Properties of Solid Self-Microemulsifying Drug Delivery Systems.

Self-microemulsifying drug delivery systems (SMEDDS) offer potential for improving the oral bioavailability of poorly water-soluble drugs. However, their susceptibilities during long term storage and in vivo precipitation issues limit their successful commercial application. To overcome these limitations, SMEDDS can be solidified with solid carriers, thus producing solid self-microemulsifying drug delivery systems (S-SMEDDS). In this study, effects of various hydrophilic carriers on structural transitions and in vitro properties of S-SMEDDS were investigated in order to set up in vitro methods for screening out appropriate carriers for S-SMEDDS. Liquid SMEDDS was prepared and characterized using nimodipine as a model drug. The effects of various hydrophilic carriers on internal microstructure and solubilization of SMEDDS were investigated by conductivity measurement and in vitro dispersion test. The results showed that hydrophilic carriers including dextran 40, maltodextrin and PVP K30 seemed to delay the percolation transition of SMEDDS, allowing it to maintain a microstructure that was more conducive to drug dissolution, thus significantly increasing the solubilization of nimodipine in the self-microemulsifying system and decreasing drug precipitation when dispersed in simulated gastric fluid. S-SMEDDS of nimodipine were prepared by using spray drying with hydrophilic carriers. The effects of various hydrophilic carriers on in vitro properties of S-SMEDDS were investigated by using SEM, DSC, PXRD and in vitro dissolution. The results showed that properties of hydrophilic carriers, especially relative molecular mass of carriers, had obvious influences on surface morphologies of S-SMEDDS, reconstitution of microemulsion and physical state of nimodipine in S-SMEDDS. Considering that in vitro properties of S-SMEDDS are closely related to their pharmacokinetic properties in vivo, the simple and economical in vitro evaluation methods established in this paper can be used to screen solid carriers of S-SMEDDS well.

Improved oral bioavailability of myricitrin by liquid self-microemulsifying drug delivery systems

This study aimed to prepare a self-microemulsifying drug delivery system loaded with myricitrin (M-SMEDDS) to improve the low oral bioavailability of myricitrin. Prepared M-SMEDDS consisted of an oil phase (ethyl oleate), a surfactant (Cremophor EL35) and a co-surfactant (dimethyl carbinol). M-SMEDDS was characterized using the particle size, zeta potential and encapsulation efficiency, while the pharmacokinetics studies were also investigated. The prepared M-SMEDDS exhibited stable physicochemical properties with a small average droplet size (21.68 ± 0.15 nm), negative zeta potential (−23.17 ± 1.03 mV) and high encapsulation efficiency (92.73%). The in vitro release study showed that myricitrin was significantly released from M-SMEDDS compared with the free myricitrin. The relative oral bioavailability of M-SMEDDS was 2.47-fold higher than that of the free drug. These results indicated that the preparation, in vitro and in vivo studies of M-SMEDDS could obviously improve the solubility and oral bioavailability of myricitrin. This study therefore provides preliminary evidence for further clinical research and application of M-SMEDDS.

Self-microemulsifying tablets prepared by direct compression for improved resveratrol delivery

The purpose of this study was to develop self-microemulsifying (SME-) tablets to improve resveratrol solubility whilst delivering resveratrol in a preferred tablet dosage form. Resveratrol was dissolved in liquid self-microemulsifying drug delivery system (SMEDDS) (10% w/w) and solidified through adsorption on several different solid carriers. Two ranges of synthetic amorphous silica (Sylysia® 290, 350, 470, 580; Syloid® 244FP, AL-1FP) as well as granulated magnesium aluminometasilicate (Neusilin® US2) were screened for their SMEDDS adsorbent capacity. The most efficient carrier from every range was chosen for further SME-tablet development. To counteract the high ratio of liquid in SME-tablets, additional dry binders (microcrystalline cellulose, copovidone) were added to the tableting mixture, as well as superdisintegrant (croscarmellose sodium) and lubricant (magnesium stearate). Finally, approx. 600 mg tablets were directly pressed using 12 mm flat face punch, containing 41.75% SMEDDS. Overall, all tablets exhibited sufficient hardness (>50 N), although it was negatively affected by higher compression force. Tablets with Neusilin® US2 proved to have highest hardness, as granulated structure of Neusilin® US2 provided best compaction properties needed for successful direct compression of tablets. All prepared SME tablet formulations disintegrated in under 10 min and formed microemulsions (droplet size < 100 nm) upon dilution with water, with Neusilin® US2 tablets exhibiting the lowest droplet size (<30 nm). While conventional dissolution test indicated incomplete resveratrol release from solid carriers in both pH 1.2 and 6.8 media, no difference fatty acid amount titrated during fasted state in vitro lipolysis between liquid and solid SMEDDS was observed. Moreover, accelerated stability tests confirmed over 90% of trans-resveratrol remained in solid SMEDDS following 90 days at 40 °C, with no crystallization of resveratrol observed during that time. To sum up, through adsorption on solid carriers, in particular Neusilin® US2, SMEDDS was successfully transformed into a directly compressible mixture and tableted without the loss of its self-microemulsifying ability.

Preparation and Pharmacokinetics Evaluation of Solid Self-Microemulsifying Drug Delivery System (S-SMEDDS) of Osthole.

The study was performed aiming to enhance the solubility and oral bioavailability of poorly water-soluble drug osthole by formulating solid self-microemulsifying drug delivery system (S-SMEDDS) via spherical crystallization technique. Firstly, the liquid self-microemulsifying drug delivery system (L-SMEDDS) of osthole was formulated with castor oil, Cremophor RH40, and 1,2-propylene glycol after screening various lipids and emulsifiers. The type and amount of polymeric materials, good solvents, bridging agents, and poor solvents in S-SMEDDS formulations were further determined by single-factor study. The optimal formulation contained 1:2 of ethyl cellulose (EC) and Eudragit S100, which served as matrix forming and enteric coating polymers respectively. Anhydrous ethanol and dichloromethane with a ratio of 5:3 are required to perform as good solvent and bridging agent, respectively, with the addition of 0.08% SDS aqueous solution as poor solvent. The optimized osthole S-SMEDDS had a high yield (83.91 ± 3.31%) and encapsulation efficiency (78.39 ± 2.25%). Secondly, osthole L-SMEDDS was solidified to osthole S-SMEDDS with no significant changes in terms of morphology, particle size, and zeta potential. In vitro release study demonstrated a sustained release of the drug from osthole S-SMEDDS. Moreover, in vivo pharmacokinetic study showed that the Tmax and mean residence time (MRT(0-t)) of osthole were significantly prolonged and further confirmed that osthole S-SMEDDS exhibited sustained release effect in rabbits. Comparing with osthole aqueous suspension and L-SMEDDS, osthole S-SMEDDS increased bioavailability by 205 and 152%, respectively. The results suggested that S-SMEDDS was an effective oral solid dosage form, which can improve the solubility and oral bioavailability of poorly water-soluble drug osthole.

Development and Optimization of Piroxicam-loaded Solid Self-micro emulsifying Drug Delivery System

The aim of present study was to formulate and evaluate self-microemulsifying drug delivery system containing piroxicam and to use the ability of porous magnesium alumina metasilicate as a solid carrier for self-micro emulsifying drug delivery system. It was developed to resolve the problems of piroxicam such as low water solubility, low bioavailability and gastrointestinal irritation. Self-micro emulsifying drug delivery system containing varying proportions of Capmul MCM, Cremophor EL and Transcutol-P were prepared and optimized using response surface methodology of Design-Expert® software version 10 stat-ease. Liquid self-microemulsifying drug delivery systems were subjected to in vitro evaluation, including self-emulsification efficiency study, droplet size, zeta potential measurement and in vitro drug release studies. Solid self-micro emulsifying drug delivery system was prepared by adding liquid self-micro emulsifying drug delivery system with Neusilin US2 and filled in hard gelatin capsule. The optimized formulation consists of 28.26 % of Capmul MCM, 44.16 % of Cremophor EL and 27.58 % of Transcutol-P. The results showed that the drug release profile of piroxicam from the self-microemulsifying drug delivery formulations was higher than the pure piroxicam powder. The release of piroxicam was rapid and complete. Solid self-micro emulsifying drug delivery systems after filled in hard gelatin capsule, predicted to be a promising technique to deliver a liquid formulation in solid dosage form.

Development of solidified self-microemulsifying drug delivery systems containing l-tetrahydropalmatine: Design of experiment approach and bioavailability comparison

The study first aimed to apply a design of experiment (DoE) approach to investigate the influences of excipients on the properties of liquid self-microemulsifying drug delivery system (SMEDDS) and SMEDDS loaded in the pellet (pellet-SMEDDS) containing l-tetrahydropalmatine (l-THP). Another aim of the study was to compare the bioavailability of l-THP suspension, liquid SMEDDS and pellet-SMEDDS in the rabbit model. By using Central Composite Face design (CCF), the optimum ratio of Capryol 90, and Smix `(Cremophor RH 40: Transcutol HP) in the formulation of SMEDDS was determined. This optimum SMEDDS was absorbed on the solid carrier (Avicel or Aerosil) for the preparation of pellet-SMEDDS by extrusion and spheronization method. The ANOVA table indicated that Avicel was more effective than Aerosil, the traditional solid carrier, in both terms of preservation of dissolution rate of l-THP from the original SMEDDS and pelletization yield. Results obtained from scanning electron microscopy (SEM) indicated that the existence of liquid SMEDDS droplets on the surface of pellet-SMEDDS was due to the absorption on Avicel. The powder X-ray diffractometry proved the amorphous state of l-THP in pellet-SMEDDS. Pharmacokinetic study in the rabbit model using liquid chromatography tandem mass spectrometry showed that the SMEDDS improved the oral bioavailability of l-THP by 198.63% compared to l-THP suspension. Besides, pharmacokinetics study also proved that the mean relative bioavailability (AUC) and mean maximum concentration (Cmax) of pellet-SMEDDS were not significantly different from the original liquid SMEDDS (p > 0.05).

Systematic development of design of experiments (DoE) optimised self-microemulsifying drug delivery system of Zotepine

The aim of present investigation is to improve dissolution rate of poor soluble drug Zotepine by a self-microemulsifying drug delivery system (SMEDDS). Ternary phase diagram with oil (Oleic acid), surfactant (Tween 80) and co-surfactant (PEG 400) at apex were used to identify the efficient self-microemulsifying region. Box–Behnken design was implemented to study the influence of independent variables. Principal Component Analysis was used for scrutinising critical variables. The liquid SMEDDS were characterised for macroscopic evaluation, % Transmission, emulsification time and in vitro drug release studies. Optimised formulation OL1 was converted in to S-SMEDDS by using Aerosil® 200 as an adsorbent in the ratio of 3:1. The S-SMEDDS was characterised by SEM, DSC, globule size (152.1 nm), zeta-potential (−28.1 mV), % transmission study (98.75%), in vitro release (86.57%) at 30 min. The optimised solid SMEDDS formulation showed faster drug release properties as compared to conventional tablet of Zotepine.

Preparation and Evaluation of Liquid and Solid Self-Microemulsifying Drug Delivery System of Mebendazole

The aim of present study was to develop solid and liquid self-microemulsifying drug delivery system of poorly water soluble drug mebendazole using Aerosil 200 as solid carrier. Microemulsions are clear, stable, isotropic liquid mixtures of oil, water and surfactant, frequently in combination with a co-surfactant having droplet size range usually in the range of 20-250 nm. Oleic acid, tween 80 and polypropylene glycol were selected as oil, surfactant and co-surfactant respectively and for preparation of stable SMEDDS, micro emulsion region was identified by constructing pseudo ternary phase diagram containing different proportion of surfactant: co-surfactant (1:1, 2:1 and 3:1), oil and water. In brief S/ CoS mix means surfactant to co-surfactant and oil were mixed at ratio of 1:9, 2:8, 3:7, 4:6, 5:5, 6:4, 7:3, 8:2 and 9:1 manner. To the resultant mixtures, water was added drop wise till the first sign of turbidity in order to identify the end point and after equilibrium; if the system became clear then the water addition was continued. Prepared optimised formula of microemulsion was evaluated for SEM, particle size analysis, polydispersity index, phase separation, viscosity determination, zeta potential, in- vitro dissolution study and in- vivo studies. The optimized microemulsion was converted into solid form by Spray Drying technique by using Aerosil 200 as solid carrier. Prepared SMEDDS was characterized for same parameters as that of microemulsion. Solid SMEDDS of mebendazole prepared using Aerosil 200 by spray drying technique showed good drug content uniformity. After reconstitution it formed microemulsion with micrometric range. In-vitro drug release and in-vivo plasma drug concentration of microemulsion and SMEDDS was much higher than that of marketed praparation. Hence lipid based drug delivery system may efficiently formulate microemulsion and it can be solidified easily by spray drying technique which enhances dissolution rate and thus concomitantly bioavailability. In conclusion ,self micro emulsifying drug delivery system has become promising tool to overcome shortcomings associated with conventional delivery.&#x0D; Kew words: Self-microemulsifying drug delivery system, Microemulsion, Mebendazole.

Potential of microemulsified entacapone drug delivery systems in the management of acute Parkinson's disease

ObjectiveTo design solid self-microemulsifying drug delivery system (S-SMEDDS) of entacapone and evaluate for its anti-Parkinson's potentials. MethodsSolubility studies were performed in various vehicles i.e., oils, surfactants and co-surfactants and pseudo-ternary phase diagrams were plotted to understand the microemulsion formation region. Liquid self-microemulsifying drug delivery systems (SMEDDS) were developed using gingelly and rice bran oil as lipid vehicles, Tween 80 and Span 20 as surfactants and glycerin, propylene glycol as co-surfactants. They were characterized by Fourier transform infrared spectroscopy, pH, viscosity, zeta potential, polydispersibility index and droplet size analysis and evaluated for drug content, in-vitro release, in-vitro diffusion and ex-vivo permeation. Optimized liquid SMEDDS were converted into S-SMEDDS by adsorption and melt granulation procedures. Characterization by differential scanning calorimetry, SEM, micrometrics, reconstitution property, moisture content and evaluation by drug content, drug release kinetics and shelf-life were performed for S-SMEDDS. Parkinsonism was induced and pharmacodynamic potentials of S-SMEDDS were evaluated. ResultsS-SMEDDS formulation AG8 had shown the highest drug release of 90.92% within 60 min. Pharmacodynamic studies also proved the efficiency of entacapone S-SMEDDS against Parkinsonism. ConclusionsEntacapone S-SMEDDS is an effective drug delivery system that offers more predictable and extensive drug release with enhanced shelf-life in the treatment of acute Parkinsonism.

Development of self-microemulsifying drug delivery system of mebendazole by spray drying technology: Characterization, in vitro and in vivo evaluation

ABSTRACTIn this study, a novel liquid self-microemulsifying drug delivery system (SMEDDS) containing mebendazole was formulated and further developed into a solid form by a spray drying method using Aerosil 200 as the solid carrier. The optimum liquid SMEDDS consisted of Labrafil 2125 CS, Tween 20, and Maisine 35-1 as the oil phase, the surfactant, and the cosurfactant, respectively. The formulated SMEDDS was completely emulsified or dispersed within a minute. All formulations were dissolved within 1 h using 0.1 N HCl as dissolution medium, whereas pure drug was less significantly dissolved in this time period. The droplet size was found to be within 250 nm for solid forms of SMEDDS. Solid state characterization was performed by scanning electron micrograph, differential scanning calorimetry, and X-ray powder diffraction. After oral administration to Wistar rats, mebendazole in the solid SMEDDS resulted in the significant improvement in bioavailability compared with that of pure drug analyzed by RP-HPLC. The optimized formulation showed 24.87 folds increase in bioavailability as compared to pure drug and 8.39 folds increase in bioavailability in comparison to marketed tablet of mebendazole. The optimized batch has found to be 3.1726 years of shelf life. In conclusion, the solid SMEDDS is a promising solid dosage form for poorly water-soluble and low bioavailability drugs.

DESIGN AND EVALUATION OF ROSUVASTATIN SMEDDS FOR ENHANCING SOLUBILITY AND DISSOLUTION RATE

The objective of present study was to improve solubility and dissolution rate of rosuvastatin by formulating it as a self micro emulsifying drug delivery system (SMEDDS). The SMEDDS were prepared by using capmul McM and capryol 90 as oils Polaxomer 407 as surfactant and Transcutol hP and Soluphor P as co-surfactants. The liquid SMEDDS were then converted into free flowing powder by adsorbing onto solid carriers like magnesium aluminium silicate. The prepared SMEDDs were further evaluated for particle size, phase separation, droplet size, drug content and for in vitro drug release. From the results, it was observed that the SMEDDs were found to be stable. Among the prepared SMEDDS the formulations prepared with oil to co-surfactant ratios of 1:3 showed highest rates of dissolution. The FTIR and DSc analysis on optimised formulations revealed that there were no major interactions between drug and excipients.

Preparation and In Vitro/In Vivo Evaluation of Puerarin Solid Self-Microemulsifying Drug Delivery System by Spherical Crystallization Technique.

The aim of this work was to establish a method for preparing stable and controllable solid self-microemulsifying drug delivery system (S-SMEDDS) by spherical crystallization technique, which was explored for promoting the dissolution, oral bioavailability, and process efficiency. Solubility test, preparation of liquid self-microemulsifying drug delivery system (L-SMEDDS), and the obtained ternary phase diagrams test have been performed to screen and optimize the composition of LSMEDDS. The optimized formulation was used to prepare puerarin solid self-microemulsifying drug delivery system (Pue-SSMEDDS) by spherical crystallization technique. Droplet size and morphological analysis of the optimal Pue-SSMEDDS were determined to evaluate the final formulation. And the Pue-SSMEDDS was also assessed by flowability study, angle of repose, Carr's index, and flow velocity. Furthermore, the vitro dissolution and pharmacokinetic profile in vivo were analyzed. The study in vitro showed the Pue-SSMEDDS could disperse in the dispersion medium within 60s and was spherical with the particle size of 19.66nm and zeta potential of -28.3mV. It could keep stable at low temperature and seal condition for 3months. In vivo pharmacokinetic experiments of rats, the mean plasma concentration of self-microemulsion group was much higher than that of conventional tablets and could play a long-lasting efficacy, while there was no significant difference between the LSMEDDS and S-SMEDDS. The results suggested the potential of S-SMEDDS could improve the oral bioavailability of poorly water-soluble drug, such as puerarin.

Enhancement of solubility and therapeutic potential of poorly soluble lovastatin by SMEDDS formulation adsorbed on directly compressed spray dried magnesium aluminometasilicate liquid loadable tablets: A study in diet induced hyperlipidemic rabbits

The aim of present study was to formulate and evaluate a self-microemulsifying drug delivery systems (SMEDDS) containing lovastatin and to further explore the ability of porous Neusilin® US2 tablet as a solid carrier for SMEDDS. SMEDDS formulations of varying proportions of peceol, cremophor RH 40 and transcutol-P were selected and subjected to in-vitro evaluation, including dispersibility studies, droplet size, zeta potential measurement and release studies. The results indicated that the drug release profile of lovastatin from SMEDDS formulations was statistically significantly higher (p-value < 0.05) than the plain lovastatin powder. Thermodynamic stability studies also confirmed the stability of the prepared SMEDDS formulations. The optimized formulation, which consists of 12% of peceol, 44% of cremophor RH 40, and 44% of transcutol-P was loaded into directly compressed liquid loadable tablet of Neusilin® US2 by simple adsorption method. In order to determine the ability of Neusilin® US2 as a suitable carrier pharmacodynamics study were also carried out in healthy diet induced hyperlipidemic rabbits. Animals were administered with both liquid SMEDDS and solid SMEDDS as well. From the results obtained, Neusilin® was found to be a suitable carrier for SMEDDS and was equally effective in reducing the elevated lipid profile. In conclusion, liquid loadable tablet (LLT) is predicted to be a promising technique to deliver a liquid formulation in solid state.

Development and optimization of self microemulsifying drug delivery of domperidone

The present investigation is aimed to develop self-microemulsifying drug delivery system (SMEDDS) to improve the in vitro dissolution of a BCS (Biopharmaceutical Classification System) class II anti emetic agent, domperidone. Solubility study was performed to identify the ingredients showing highest solubility of domperidone. The ternary phase diagrams were plotted for selected components to identify the area of microemulsion existence. D-optimal mixture experimental design was applied to optimize a liquid SMEDDS using formulation variables; the oil phase X1 (Oleic acid), the surfactant X2 (Labrasol) and the co-surfactant X3 (Transcutol HP). The liquid SMEDDS were evaluated for droplet size, emulsification time, % transmittance and drug release. Stability study was performed at 40 °C/75% RH. Liquid formulation was solidified by adsorption on carrier Aerosil 300. Solid SMEDDS was evaluated and compared with liquid SMEDDS and marketed formulation. Oleic acid was selected as oil, Labrasol as surfactant and Transcutol HP as co-surfactant for formulation of SMEDDS. The optimized batch showed best results in terms of smaller droplet size (&lt;170 nm), emulsification time (&lt;40 s) and drug release (&gt;85% in 15 min) and was stable for 3 months. Solid SMEDDS containing Aerosil 300 showed good flow properties and uniform drug content. XRPD study revealed that the crystalline drug was converted to amorphous form in solid SMEDDS. The rate and extent of drug dissolution from solid SMEDDS was significantly higher than pure drug and commercial tablet formulation. The results demonstrate the potential of SMEDDS as a means of improving solubility, dissolution and hence the bioavailability.

Liquid and solid self-microemulsifying drug delivery systems for improving the oral bioavailability of andrographolide from a crude extract of Andrographis paniculata

The purpose of this study was to develop self-microemulsifying formulations of an Andrographis paniculata extract in liquid and pellet forms for an improved oral delivery of andrographolide. The optimized liquid self-microemulsifying drug delivery system (SMEDDS) was composed of A. paniculata extract (11.1%), Capryol 90 (40%), Cremophor RH 40 (40%) and Labrasol (8.9%). This liquid SMEDDS was further adsorbed onto colloidal silicon dioxide and microcrystalline cellulose, and converted to SMEDDS pellets by the extrusion/spheronization technique. The microemulsion droplet sizes of the liquid and pellet formulations after dilution with water were in the range of 23.4 and 30.3nm. The in vitro release of andrographolide from the liquid SMEDDS and SMEDDS pellets was 97.64% (SD 1.97%) and 97.74% (SD 3.36%) within 15min, respectively while the release from the initial extract was only 10%. The oral absorption of andrographolide was determined in rabbits. The Cmax value of andrographolide from the A. paniculata extract liquid SMEDDS and SMEDDS pellet formulations (equivalent to 17.5mg/kg of andrographolide) was 6-fold and 5-fold greater than the value from the initial extract in aqueous suspension (equivalent to 35mg/kg of andrographolide), respectively. In addition, the AUC0–12h was increased 15-fold by the liquid SMEDDS and 13-fold by the SMEDDS pellets compared to the extract in aqueous suspension, respectively. The results clearly indicated that the liquid and solid SMEDDS could be effectively used to improve the dissolution and oral bioavailability that would also enable a reduction in the dose of the poorly water soluble A. paniculata extract.

A new self-microemulsifying mouth dissolving film to improve the oral bioavailability of poorly water soluble drugs

A new self-microemulsifying mouth dissolving film (SMMDF) for poorly water-soluble drugs such as indomethacin was developed by incorporating self-microemulsifying components with solid carriers mainly containing microcrystalline cellulose, low-substituted hydroxypropyl cellulose and hypromellose. The uniformity of dosage units of the preparation was acceptable according to the criteria of Chinese Pharmacopoeia 2010. The SMMDF was disintegrated within 20 s after immersion into water, released completely at 5 min in the dissolution medium and achieved microemulsion particle size of 28.81 ± 3.26 nm, which was similar to that of liquid self- microemulsifying drug delivery system (SMEDDS). Solid state characterization of the SMMDF was performed by SEM, DSC and X-ray powder diffraction. Results demonstrated that indomethacin in the SMMDF was in the amorphous state, which might be due to self-microemulsifying ingredients. Pharmacokinetic parameters in rats including Tmax, Cmax, AUC were similar between the SMMDF and liquid SMEDDS. AUC and Cmax from the SMMDF were significantly higher than those from the common mouth dissolving film or the conventional tablet, and Tmax from SMMDF group was also significantly decreased. These findings suggest that the SMMDF is a new promising dosage form, showing notable characteristics of convenience, quick onset of action and enhanced oral bioavailability of poorly water-soluble drugs.

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.

Development and evaluation of self-microemulsifying liquid and pellet formulations of curcumin, and absorption studies in rats

This study describes the development and characterization of self-microemulsifying drug delivery systems (SMEDDS) in liquid and pellet forms that result in improved solubility, dissolution, and in vivo oral absorption of the poorly water-soluble compound curcumin. Solubility of curcumin was determined in various vehicles, including oils, surfactants and co-surfactants. Pseudo-ternary phase diagrams were constructed to identify the most efficient self-emulsification region. The optimized SMEDDS used for curcumin formulations in liquid and pellet forms contained 70% mixtures of two surfactants: Cremophor EL and Labrasol (1:1), and 30% mixtures of oil: Labrafac PG and Capryol 90 (1:1). The curcumin-SMEDDS in liquid and pellet formulations rapidly formed fine oil-in-water microemulsions, with particle size ranges of 25.8–28.8 nm and 29.6–32.8 nm, respectively. The in vitro rate and extent of release of curcumin from liquid SMEDDS and SMEDDS pellets was about 16-fold higher than that of unformulated curcumin. Plasma concentration–time profiles from pharmacokinetic studies in rats dosed with liquid and pelleted SMEDDS showed 14- and 10-fold increased absorption of curcumin, respectively, compared to the aqueous suspensions of curcumin. Curcumin-SMEDDS liquid and curcumin-SMEDDS pellets were found to be stable up to 6 months under intermediate and accelerated conditions. These studies demonstrate that the new self-microemulsifying systems in liquid and pellet forms are promising strategies for the formulation of poorly soluble lipophilic compounds with low oral bioavailability.

The Use of Liquid Self-Microemulsifying Drug Delivery Systems Based on Peanut Oil/Tween 80 in the Delivery of Griseofulvin

Peanut oil and Tween 80 blends devoid of any cosurfactant were employed in the formulation of different batches of liquid self-microemulsifying drug delivery systems (LSMEDDS) and their suitability as vehicles for the delivery of a typical lipophilic drug—griseofulvin—was investigated. The LSMEDDS were evaluated using the following parameters: phase separation, globule size, viscosity, solubility of griseofulvin, and partition coefficient. The release profile of griseofulvin from the optimized LSMEDDS was evaluated in citrate/phosphate buffer solutions of pH 2.0, pH 6.5, and pH 7.4. The results obtained indicated that there was significantly higher (α ≤ 0.05) percentage cumulative amounts of griseofulvin released from the LSMEDDS in comparison with that released from peanut oil alone. The release of griseofulvin from the LSMEDDS into aqueous media of pH 6.5 and pH 7.4 showed enhanced and controlled dissolution of the drug from the formulation. Incorporation of griseofulvin into this proposed formulation is suggested as a strategy to overcome the irregular dissolution and absorption behaviors often associated with conventional griseofulvin tablets.