Liquid Self-microemulsifying Drug Delivery System Research Articles

Formulation, Optimization and Evaluation of Solid SMEDDS of Pioglitazone

This investigation assessed 32 formulations of liquid self-microemulsifying drug delivery system (L-SMEDDS) for pioglitazone (PGZ). The optimal PLS12 formulation comprises 40% capmul MC8 (oil), 40% cremophore RH40 (surfactant), and 20% PEG (co-surfactant). PLS12 exhibited approximately 75 nm droplet size, below 200 nm, and a PDI of 0.47, indicating nanosized droplets with uniform distribution. The formulation demonstrated stability, and achieved supreme drug loading capacity. The enhanced L-SMEDDS was solidified into solidified SMEDDS utilizing Sylloid 244 FP, subsequently in a free-flowing powder without drug interactions. Tablets were successfully formulated by incorporating S-SMEDDS with diverse tableting excipients. The selected tablet batch passed quality control and stability tests. The tablet exhibited a rapid and pH-independent release profile. The combined impact of SMEDDS and tablets collectively enhanced the solubility and dissolution of PGZ hydrochloride

Formulation and in vitro evaluation of meloxicam as a self-microemulsifying drug delivery system.

Background: The nonsteroidal anti-inflammatory medication meloxicam (MLX) belongs to the oxicam family and is used to reduce inflammation and pain. The aim of this study was to improve MLX's dispersibility and stability by producing it as a liquid self-microemulsifying drug delivery system since it is practically insoluble in water. Methods: Five different formulations were made by adjusting the amounts of propylene glycol, Transcutol P, Tween 80, and oleic acid oil and establishing a pseudo-ternary diagram in ratios of 1:1, 1:2, 1:3, 1:4, and 3:4, respectively. All of the prepared formulations were tested for a variety of properties, including thermodynamicstability, polydispersity index, particle size distributions, dilution resistance, drug contents, dispersibility, in vitro solubility of the drug, and emulsification time. Results: F5 was chosen as the optimal MLX liquid self-microemulsion due to its higher drug content (99.8%), greater in vitro release (100% at 40 min), smaller droplet size (63 nm), lower polydispersity index (PDI) value (0.3), and higher stability (a zeta potential of -81 mV). Conclusions: According to the data provided here, the self-microemulsifying drug delivery system is the most practical method for improving the dispersibility and stability of MLX.

Formulation and in vitro evaluation of meloxicam as a self-microemulsifying drug delivery system

Background: The nonsteroidal anti-inflammatory medication meloxicam (MLX) belongs to the oxicam family and is used to reduce inflammation and pain. The aim of this study was to improve MLX's dispersibility and stability by producing it as a liquid self-microemulsifying drug delivery system since it is practically insoluble in water. Methods: Five different formulations were made by adjusting the amounts of propylene glycol, Transcutol P, Tween 80, and oleic acid oil and establishing a pseudo-ternary diagram in ratios of 1:1, 1:2, 1:3, 1:4, and 3:4, respectively. All of the prepared formulations were tested for a variety of properties, including thermodynamic stability, polydispersity index, particle size distributions, dilution resistance, drug contents, dispersibility, in vitro solubility of the drug, and emulsification time. Results: F5 was chosen as the optimal MLX liquid self-microemulsion due to its higher drug content (99.8%), greater in vitro release (100% at 40 min), smaller droplet size (63 nm), lower polydispersity index (PDI) value (0.3), and higher stability (a zeta potential of -81 mV). Conclusions: According to the data provided here, the self-microemulsifying drug delivery system is the most practical method for improving the dispersibility and stability of MLX.

Self-microemulsifying Drug Delivery System for Solubility and Bioavailability Enhancement of Eprosartan Mesylate: Preparation, In-vitro, and In-vivo Evaluation.

Formulations of eprosartan mesylate with a surfactant, like Kolliphor HS 15, an oil phase like Labrafil M 1944 CS, and a cosurfactant Transcutol HP by employing a liquid self-microemulsifying drug delivery system (SMEDDS) after screening several vehicles have been studied. This study aimed to prepare a liquid self-microemulsifying drug delivery system for increasing the solubility and bioavailability of a poorly water-soluble eprosartan mesylate. The micro-emulsion unit, achieved through the phase diagram and augmented with the central-composite design (CCD) surface response process, was adjusted into SMEDDS by lyophilization using sucrose as a cryoprotective agent. Particle size, self-emulsification time, polydispersion index (PDI), zeta potential, differential scanning calorimeter (DSC) screening, in-vitro drug release, and in-vivo pharmacokinetics were the essential features of the formulations. The subsequent DSC experimentation indicated that the drug was integrated into S-SMEDDS. Eprosartan mesylate loaded SMEDDS formulation showed greater in-vitro and in-vivo drug release than conventional solid doses. SMEDDS has reported effectiveness in reducing the impact of pH of eprosartan mesylate, thereby improving its release efficiency. The HPLC method was successfully implemented to assess eprosartan mesylate concentration in Wister rat plasma after oral administration of commercial tablet EM, SMEDDS, and eprosartan mesylate. The pharmacokinetics parameters for rats were Cmax 1064.91 ± 225 and 1856.22 ± 749 ngmL-1, Tmax 1.9 ± 0.3 hr, and 1.2 ± 0.4 hr and AUC0~t were 5314.36 ± 322.61 and 7760.09 ± 249 ng/ml hr for marketed tablets and prepared SSMEDDS, respectively. When determined by AUC0~1, the relative bioavailability of eprosartan mesylate S-SMEDDC was 152.09 ± 14.33%. The present study reports the formulation of a self-microemulsifying drug delivery system for enhancing the solubility and bioavailability of a poorly water-soluble eprosartan mesylate in an appropriate solid dosage form.

Formulation and Evaluation of the Fenofibrate Spray-dried Emulsion Tablets

The present research work deals with the development of a self-micro emulsifying drug delivery system (SMEDDS) of Fenofibrate (FF) followed by spray drying to form solid SMEDDS and tablets with enhanced solubility and dissolution. FF is BCS class II drug with low bioavailability and low aqueous solubility. The solubility of the FF can be improved by formulating SMEDDS. Liquid SMEDDS were developed by adding the drug in oleic acid, Tween 80, and Transcutol HP to get a clear solution. In the spray drying method, dextran was used to form the granules. Further, direct compression method was used to manufacture the tablets. The spray-dried product containing solid SMEDDS of FF showed nearly 30-fold solubility enhancement in distilled water in comparison to pure FF. The optimized formulation containing solid SMEDDS of FF (F9) showed an increased dissolution rate (100% drug release at 60 minutes) in comparison to conventional tablets. The optimized batch showed excellent stability at the accelerated condition for the period of 3 months. The current research work demonstrates spray drying as a potential approach to transfer the liquid SMEDSS to a solid SMEDDS with an enhanced solubility and dissolution rate.

Formulation and Evaluation of Fenofibrate Dry Emulsion Tablets by Freeze Drying Method

Fenofibrate (FF) is a lipid-lowering agent classified in the biopharmaceutics classification system (BCS) class II with lower solubility and higher permeability. This research work deals with developing FF containing liquid self-micro emulsifying drug delivery system (L-SMEDDS) and converting it into solid SMEDDS (S-SMEDDS) using a lyophilization technique followed by the manufacturing of tablets with enhanced solubility and dissolution rate. L-SMEDDS of FF were manufactured using Tween 80, oleic acid, and transcutol. With the help of the lyophilization technique, this L-SMEDDS was converted to S-SMEDDS using microcrystalline cellulose and finally, immediate-release tablets were developed using S-SMEDDS. The L-SMEDDS showed excellent stability due to zeta potential of -1.69 mV and a globule size of 250 μm. The lyophilized S-SMEDDS of FF showed nearly 58-fold solubility enhancement in distilled water in comparison to pure FF due to the formation of amorphous material confirmed in the X-ray diffraction (XRD) study. The F9 formulation showed 100% drug release within 40 minutes with enhanced dissolution properties compared to conventional tablets. The optimized formulation was robust and stable at the accelerated condition for 3 months. The current research work demonstrates lyophilization as a potential approach to convert the L-SMEDSS to a S-SMEDDS with an enhanced solubility and dissolution rate.

Formulation Development and Optimization of Blonanserin Liquid SMEDDS using D-Optimal Mixture Design

Background: Blonanserin is an atypical antipsychotic potent antagonist of dopamine-D2 and D3 receptors with low aqueous solubility BCS class II drugs. Objective: The present research aims to develop and optimize the Blonanserin-loaded liquid selfmicro emulsifying drug delivery system (SMEDDS) to improve its in vitro drug release by D-optimal mixture design. Methods: Saturation solubility of Blonanserin was checked in various oils, surfactants, and cosurfactants. The pseudo-ternary phase diagram was developed to identify the region of the microemulsion. Trial batches were designed to determine dependent and independent variables in the formulation. DOptimal Mixture design applies for optimization and minimized trials. The amount of oil(X1), surfactant( X2), and co-surfactant(X3) were selected as independent variables, and solubility(Y1) and in vitro percentage cumulative drug release(Y2) and size of globule(Y3) after 250 times dilution were selected as the dependant variable. The level of the independent variables in the design will be selected based on the drug's phase diagram, trial batches, and solubility. The developed SMEDDS was then evaluated for globule size, transparency, self-emulsification time, in vitro dissolution, and relative dissolution of the final formulation with marketed products and a pure drug. Results: BLN shows the highest solubility in (1:1) Captex 200P: Capmul MCM (oil), Tween 20 (surfactant), and Ethanol (cosurfactant). Trial batches were shown at 1:9, 2:8, and 3:7 oil to surfactant and cosurfactant ratios suitable for optimization. Optimization using a D-optimal mixture design gives 11 run batches and the resulting surface and contour plot suggest the best design space. The optimized formula given by the mixture design of the target formulation had maximum drug solubility, maximum drug release, and minimum globule size. Optimized formula containing Blonanserin, Captex 200P: Capmul MCM (1:1) Mixture (23% v/v), Tween 80 (57% v/v), and Ethanol (20% v/v) having 94.72% in vitro diffusion within 30 min with 21 nm globule size. Optimized liquid SMEDDS have a higher in-vitro diffusion rate than marketed products and pure drugs. Conclusion: Blonanserin liquid SMEDDS was successfully developed with high solubility, nanoglobule size, and improvement in in-vitro diffusion rate and vice versa for improvement in bioavailability of the drug.

SELF-MICRO EMULSIFYING DRUG DELIVERY SYSTEM OF URSOLIC ACID: FORMULATION DEVELOPMENT, CHARACTERIZATION, PHARMACOKINETIC AND PHARMACODYNAMIC STUDIES FOR DIABETIC COMPLICATIONS

Objective: The objective of this study was to develop, characterize, and conduct pharmacokinetic and pharmacodynamic studies on ursolic acid solid self microemulsifying drug delivery system (UA-S-SMEDDS) for the treatment of diabetic complications. Methods: Liquid self microemulsifying drug delivery system (L-SMEDDS) were made with Capryol 90 as an oil, Cremophor EL as a surfactant, and polyethylene glycol (PEG) 400 as a co-surfactant. The surfactant and co-surfactant (Smix) ratios were calculated using a pseudo ternary phase diagram. At different pH levels and with water, the globule size, polydispersity index (PDI), zeta potential (ZP), and dilution were all assessed. S-SMEDDS has developed adsorption to a solid carrier by utilizing L-SMEEDS formulation. The powder properties, liquid retention potential, globule size, PDI, ZP, assay, and pharmacokinetic studies were all evaluated. The pharmacodynamic investigations of the S-SMEDDS formulation in streptozotocin (STZ) induced Wistar rats were evaluated using malondialdehyde (MDA) and glutathione (GSH) determination in tissues and section studies. Results: S-SMEDDS formulation was successfully developed with a droplet size of 163.4±1.475 nm, PDI of 0.251±0.042, a ZP of-21.3±1.02, an assay of 96.21±0.75%. The release studies showed 26.28% (0.1N HCl) and 83.57% (6.8 phosphate buffer) were released in 15 min. When comparing the pharmacokinetics of a UA-loaded S-SMEDDS to the coarse suspension, the S-SMEDDS (F2A) showed a 4.12 fold improvement in UA oral bioavailability. The pharmacodynamic results showed that S-SMEDDS was a higher recovery rate. Conclusion: The developed solid SMEDDS (F2A) formulation proved effective in treating diabetic complications in STZ induced Wistar rats by inhibiting the aldose reductase enzyme.

Novel Self-micro Emulsifying Drug Delivery System for Safe Intramuscular Delivery with Improved Pharmacodynamics and Pharmacokinetics.

Diclofenac Sodium (DS) injection is widely used in the management of acute or chronic pain and inflammatory diseases. It incorporates 20% w/v Transcutol-P as a solubilizer to make the stable injectable formulation. However, the use of Transcutol-P in high concentration leads to adverse effects such as severe nephrotoxicity, etc. Some advancements have resulted in the formulation of an aqueous-based injectable but that too used benzyl alcohol which is reported to be toxic for human use. This study aimed to develop an injectable Self-Micro Emulsifying Drug Delivery System (SMEDDS) as a novel carrier of DS for prompt release with better safety and efficacy. A solubility study was performed with different surfactants and co-surfactants. The conventional stirring method was employed for the formulation of SMEDDS. Detailed in vitro characterization was done for different quality control parameters. In vivo studies were performed using Wistar rats for pharmacokinetic evaluation, toxicological analysis, and analgesic activity. The optimized formulation exhibited good physical stability, ideal globule size (156±0.4 nm), quick release, better therapeutics, and safety, increase in LD50 (221.9 mg/kg) to that of the commercial counterpart (109.9 mg/kg). Furthermore, pre-treatment with optimized formulation reduced the carrageenan-induced rat paw oedema by 88±1.2% after 4 h, compared to 77±1.6% inhibition with commercial DS formulation. Moreover, optimized formulation significantly (p<0.05) inhibited the pain sensation in the acetic-acid induced writhing test in mice compared to its commercial equivalent with a better pharmacokinetic profile. The above findings confirmed that liquid SMEDDS can be a successful carrier for the safe and effective delivery of DS.

Formulation and Characterization of Self-Microemulsifying Drug Delivery System of Tacrolimus

Abstract&#x0D; The present investigation aimed to formulate a liquid self-microemulsifying drug delivery system (SMEDDS) of tacrolimus to enhance its oral bioavailability by improving its dispersibility and dissolution rate. Four liquid SMEDDS were prepared using maisine CC as oil phase, labrasol ALF as surfactant and transcutol HP as co-surfactant based on the solubility studies of tacrolimus in these components. The phase behavior of the components and the area of microemulsion were evaluated using pseudoternary phase diagrams. The formulations were also assessed for thermodynamic stability, robustness to dilution, self-emulsification time, drug content, globule size and polydispersity index. The prepared SMEDDS formulations exhibited improved drug release compared to the pure drug powder. From this study, it was concluded that using a composition of 10% maisine CC, 67.5% labrasol ALF and 22.5% transcutol produced a liquid SMEDDS with good thermodynamic stability and enhanced in-vitro drug release profiles compared with pure tacrolimus powder. All which supports the use of self-micro emulsifying drug delivery systems as a promising approach to improve solubility, dissolution and stability of poorly soluble drugs like tacrolimus.

Can APIs that are Poorly Water‐ and Oil‐Soluble Benefit from Incorporation into SMEDDS? The Case of Dipyridamole

AbstractThe aim of this study is to develop a self‐microemulsifying drug delivery system (SMEDDS) for the model active pharmaceutical ingredient (API) dipyridamole using exclusively excipients suitable for oral administration and nonvolatile cosolvents. Dipyridamole is a poorly water‐soluble and poorly oil‐soluble compound, which made it an atypical candidate for development of a lipid‐based drug delivery system (LBDDS). Four SMEDDS are successfully formulated, and dipyridamole has up to 1750‐fold higher solubility in the SMEDDS compared to water. Incorporation of 0.6–1% of dipyridamole into the SMEDDS does not considerably affect the droplet size, uniformity of droplet size distribution, and self‐emulsifying properties of the SMEDDS. The applicability of hard capsules for developing a final solid dosage form is tested by dissolution studies of dipyridamole from SMEDDS filled in gelatin and hydroxypropyl methylcellulose (HPMC) hard capsules. In addition, empty SMEDDS are filled into gelatin and HPMC hard capsules. They are stored for 16 weeks at ambient conditions and at 40 °C and 75% relative humidity. The dissolution properties and solubility of dipyridamole are considerably enhanced by incorporating dipyridamole into the SMEDDS; however, development of a final dosage form with hard capsules that are leak‐free for an extended period and at higher temperatures/humidity is still pending.Practical Applications: This study suggests that substances with low water solubility and low oil solubility can also benefit from incorporation into SMEDDS. Excipient selection needs to be considered carefully for such cases to maximize API incorporation and to ensure the self‐emulsifying properties of the formulation. In addition, only nonvolatile and orally acceptable excipients are used for preparation of SMEDDS, which is important when developing a formulation aimed for oral application. Hard capsules are a common approach for preparation of final dosage forms; however, obtaining leak‐free capsules can be challenging when liquid SMEDDS are used as filling. Storage for prolonged period and at higher temperatures/humidity is necessary for evaluation of liquid SMEDDS‐filled hard capsules.

Evaluation of Bio-Mechanistic Behavior of Liquid Self-Microemulsifying Drug Delivery System in Biorelevant Media

The aim of the study is to mechanistically investigate the drug loci, structural integrity, chemical interactions, and absorption behavior of the liquid self-microemulsifying drug delivery system (SMEDDS). The loci of drug molecules in self-forming microemulsions in biorelevant media (fasted state simulated gastric fluid and fed state simulated intestinal fluid) were investigated by 1H and 13C nuclear magnetic resonance (NMR) spectroscopy. Chemical interactions were observed through attenuated total reflectance spectroscopy (ATR). The structural integrity of self-forming microemulsions in biorelevant media was determined by small angle X-ray scattering (SAXS) and fluorescence resonance energy transfer (FRET). Morphological features of self-forming microemulsion were determined by confocal laser scanning microscopy. In vitro, lipid digestion behavior was evaluated for particle size, zeta potential, free fatty acids (FFA), and drug released through standard protocols. In-house characterizations were determined through standard methodologies. 1H and 13C NMR revealed that drug loci were found in a majority in the oily core region in the self-forming microemulsion. The ATR signifies that no inherent chemical was observed in the liquid SMEDDS and drug-loaded self-microemulsions in the biorelevant media. Structural integrity was well maintained during the dispersive and digestive phases in the gastrointestinal lumen during lipolysis in biorelevant conditions, as revealed by SAXS and FRET. An in vitro digestion study in biorelevant conditions depicts no fluctuations in size and zeta potential with a predominant release of FFA and drug, and was to be revealed physiologically acceptable for clinical applications.

Enhanced Oral Bioavailability and Improved Biological Activities of a Quercetin/Resveratrol Combination Using a Liquid Self-Microemulsifying Drug Delivery System.

Both quercetin and resveratrol are promising plant-derived compounds with various well-described biological activities; however, they are categorized as having low aqueous solubility and labile natural compounds. The purpose of the present study was to propose a drug delivery system to enhance the oral bioavailability of combined quercetin and resveratrol. The suitable self-microemulsifying formulation containing quercetin together with resveratrol comprised 100 mg Capryol 90, 700 mg Cremophor EL, 200 mg Labrasol, 20 mg quercetin, and 20 mg resveratrol, which gave a particle size of 16.91 ± 0.08 nm and was stable under both intermediate and accelerated storage conditions for 12 months. The percentages of release for quercetin and resveratrol in the self-microemulsifying formulation were 75.88 ± 1.44 and 86.32 ± 2.32%, respectively, at 30 min. In rats, an in vivo pharmacokinetics study revealed that the area under the curve of the self-microemulsifying formulation containing quercetin and resveratrol increased approximately ninefold for quercetin and threefold for resveratrol compared with the unformulated compounds. Moreover, the self-microemulsifying formulation containing quercetin and resveratrol slightly enhanced the in vitro antioxidant and cytotoxic effects on AGS, Caco-2, and HT-29 cells. These findings demonstrate that the self-microemulsifying formulation containing quercetin and resveratrol could successfully enhance the oral bioavailability of the combination of quercetin and resveratrol without interfering with their biological activities. These results provide valuable information for more in-depth research into the utilization of combined quercetin and resveratrol.

An integrated QbD based approach of SMEDDS and liquisolid compacts to simultaneously improve the solubility and processability of hydrochlorthiazide

Hydrochlorothiazide (HCTZ) is a class IV BCS drug that exhibits varying bioavailability due to poor solubility and low permeability. The first part of the present investigation was aimed to prepare liquid self-microemulsifying drug delivery system (SMEDDS) of HCTZ to improve its dissolution properties. The liquid SMEDDS was subsequently converted to self-microemulsifying tablets (SMETs) by using the liquisolid technique to facilitate the manufacturing process. Based on the solubility study and ability to form transparent microemulsion upon dilution, oleic acid, tween-20, and propylene glycol were selected as oil, surfactant, and co-surfactant respectively to form liquid SMEDDS. The central composite design was used to investigate the effect of changes in formulation composition on critical product characteristics and to optimize the SMEDDS formualtion. Neusilin US2 and Aerosil-200 were selected as carrier and coating material to prepare SMETs as they displayed the highest flowable liquid potential among all tested excipients. The prepared SMETs have acceptable tableting properties (flowability, compressibility, and compactibility) and were able to preserve self microemulsifying properties of entrapped SMEDDS formulation. The results of DSC and XRD studies suggested that better dissolution properties of SMETs formulation compared to pure drug and marketed products was possibly due to the drug either being molecularly dispersed form or presence in the amorphous state within the formulation.

DEVELOPMENT AND EVALUATION OF ZIPRASIDONE LOADED SOLID SELF-MICRO EMULSIFYING DRUG DELIVERY SYSTEM

Solid self-micro emulsification technique is the new approach for poorly water-soluble and poorly bioavailable drugs by allowing the drug substance to be incorporated into the oil phase and thus having the ability to permeate the GI membrane to a faster extent. Oleic acid, Tween 80, methanol and colloidal silicon dioxide were used as penetrant, surfactant, co-surfactant and adsorbent, respectively. The interaction between drug and excipients was examined by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). The results of DSC and FTIR studies did not reveal any possible drug-excipient interactions. The conversion of liquid self-microemulsifying drug delivery system (SMEDDS) into the solid SMEDDS increases the stability of the emulsion formulation achieved by physical adsorption of an adsorbent material. The release of drug from SMEDDS formulation is justified by in-vitro dissolution studies. SMEDDS increases the solubility of the drug and improves the bioavailability, without disturbing gastrointestinal transit. SMEDDS has the potential to provide a useful oral solid dosage form for the poorly water-soluble drug ziprasidone.

Enhancement of in vivo hypoglycemic effect of gliclazide by developing self-microemulsifying pellet dosage form

BackgroundThe present research was aimed to develop a self-microemulsifying drug delivery system (SMEDDS) pellet to increase the dissolution rate and in vivo hypoglycemic effect of gliclazide. Gliclazide belongs to BCS class 2 and it exhibits dissolution rate-limited absorption. Thus, dissolution enhancement of gliclazide from its dosage form is a prime requirement to achieve a better therapeutic effect. The solubility of gliclazide was estimated in oils, surfactants, and co-surfactants. A most effective self-emulsification region was identified using pseudoternary phase diagrams. The optimized liquid SMEDDS gliclazide formulation was converted to SMEDDS pellets using the extrusion-spheronization technique. The in vitro release and hypoglycemic effect of SMEDDS was compared with the marketed product.ResultsThe optimized liquid gliclazide SMEDDS formulations contained mixtures of Tween 80 and PEG 400 and Capmul MCM C8. The gliclazide SMEDDS in liquid preparation quickly formed a fine oil-in-water microemulsion having a globule size of 31.50 nm. In vitro release of gliclazide from SMEDDS pellets was 100.9% within 20 min. SMEDDS pellets exhibited a significant reduction in plasma glucose levels in albino mice compared to the marketed product.ConclusionThe results indicated that SMEDDS pellets could be effectively used to improve the oral delivery of gliclazide.

Self Microemulsifying Immediate Release Tablet of Azilsartan for Enhanced Dissolution

Azilsartan has solubility problem which leads to low dissolution and hence bioavailability, hence it is necessary to improve solubility of azilsartan. Objective of study was to develop self micro emulsifying tablet of azilsartan to enhance dissolution. Liquid self micro emulsifying drug delivery system (SMEDDS) was prepared using ethyl oleate, Tween 80 and Transcutol P as oil, surfactant and co-surfactant respectively. Microemulsion region was predicted by constructing a pseudo-ternary phase diagram containing a different proportion of oil, surfactant, and co-surfactant. Liquid SMEDDS was then converted to solid form (S-SMEDDS) by adsorption technique using Neusilin US2 as a solid carrier and evaluated for various pre-compression micromeritic properties. This S-SMEDDS were then compressed into immediate release tablet. Developed tablet of azilsartan were reconstituted and evaluated for % Transmittance, globule size, zeta potential. Tablets were also evaluated for post compression parameters, in-vitro dissolution study, DSC, XRD and FTIR. Reconstitution properties of self emulsifying tablet showed spontaneous micro emulsification with globule size 210 nm and-37 mV zeta potential. From results of in-vitro dissolution study, it was found that the release of azilsartan was significantly increased as compared with pure azilsartan. Study concluded that dissolution of azilsartan can be significantly improved by formulating it in to self emulsifying tablet for getting improved oral bioavailability.

Self-microemulsion Technology for Water-insoluble Drug Delivery

: According to the drug discovery, approximately 40% of the new chemical entities show poor bioavailability due to their low aqueous solubility. In order to increase the solubility of the drugs, self-micro emulsifying drug delivery systems (SMEDDS) are considered as an ideal technology for enhancing the permeability of poorly soluble drugs in GI membranes. The SMEDDS are also generally used to enhance the oral bioavailability of the hydrophobic drugs. At present, most of the self-microemulsion drugs are liquid dosage forms, which could cause some disadvantages, such as the low bioavailability of the traditional liquid SMEDDS. Therefore, solid self-micro emulsifying drug delivery systems (S-SMEDDS) have emerged widely in recent years, which were prepared by solidifying a semi-solid or liquid self-emulsifying (SE) ingredient into a powder in order to improve stability, treatment and patient compliance. The article gives a comprehensive introduction of the study of SMEDDS which could effectively tackle the problem of the water-insoluble drug, especially the development of solidification technology of SMEDDS. Finally, the present challenges and the prospects in this field were also discussed.

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.