Liquid Self-microemulsifying Drug Delivery Research Articles

Pharmacokinetic and toxicological assessment of a solid self-microemulsifying drug delivery system (S-SMEDDS) of kaempferia parviflora in rats

Kaempferia parviflora (KP), renowned as an alternative medicine, has gained widespread acclaim for its efficacy in male sexual enhancement and anti-inflammatory applications. However, methoxyflavones, its primary compound, poses challenges due to inherent low water solubility and limited oral absorption. This study aims to develop a novel solid self-microemulsifying drug delivery system for KP (KPS-SMEDDS) and to investigate the pharmacokinetic profile and acute toxicity. The liquid self-microemulsifying drug delivery system for KP (KPL-SMEDDS) was formed by combining Neobee® M − 5 (90 %) with a mixture of surfactant (10 %) consisting of Kolliphor® EL and polyethylene glycol 400 in a ratio of 1:2. Consequently, the KPL-SMEDDS was transformed into a powdered form by employing Sipernat® 22S as an absorbent in a 1:1 ratio. The developed formulations were subsequently evaluated for their physicochemical properties, in vitro dissolution tests, and in vivo oral absorption in rats by using methoxyflavones as the markers for quantitation. The findings demonstrated that the use of KPL-SMEDDS and KPS-SMEDDS improved the dissolution rate of methoxyflavones in 0.1 N HCl in comparison to KP powder. Comparative analysis revealed that the KPS-SMEDDS exhibited a significantly higher maximum drug concentration (Cmax) and area under the curve (AUC) values in comparison to the conventional KP extract. Notably, the KPS-SMEDDS formulation at an oral dose of 250 mg/kg remarkably increased the bioavailability of polymethoxyflavones up to 2.7- to 3-fold. Furthermore, acute oral toxicity assessment revealed no statistically significant alterations in clinical observations or biochemical parameters. These compelling findings underlined the potential of the KPS-SMEDDS formulation to augment the absorption and bioavailability of methoxyflavones, establishing its safety as an oral supplement.

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.

Improved oral bioavailability of febuxostat by liquid self-micro emulsifying drug delivery system in capsule shells

Febuxostat is a non-purine xanthine oxidase inhibitor which belongs to the BCS class II. Main aim of this study is to enhance dissolution and bioavailability of a drug by formulating a liquid self-micro emulsifying drug delivery system (SMEDDS) in different capsule shells. Compatability of gelatin and cellulose capsule shells was checked with different oils, surfactants and co-surfactants. Solubility studies were then carried out in selected excipients. Capryol 90, labrasol, and PEG 400 were used in a liquid SMEDDS formulation based on phase diagram and the drug loading. Further SMEDDS was characterized for zeta potential, globule size and shape, thermal stability and in vitro release. Based on the in vitro release, pharmacokinetic study was carried out using SMEDDS in gelatin capsule shells. The diluted SMEDDS had globule size of 157.9±1.5d.nm, zeta potential of -16.2±0.4mV and they were thermodynamically stable. The formulation was found stable for 12 months in capsule shells. When tested in different media (0.1N HCl and pH 4.5 acetate buffer), the in vitro release of newly produced formulations differed substantially from that of commercially available tablets, while the release rate in alkaline medium (pH 6.8) was comparable and the highest. According to in vivo findings in rats, a threefold increase in plasma concentration, a fourfold increase in AUC0-t, and a reduction in oral clearance increased fuxostat's oral bioavailability. This investigation revealed that the novel liquid SMEDDS formulation sealed in capsules has considerable potential as a vehicle for enhancing the bioavailability of febuxostat.

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 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.

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

Abstract
 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.

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.

In vitro and in vivo evaluation of poly (acrylic acid) modified mesoporous silica nanoparticles as pH response carrier for β-elemene self-micro emulsifying.

The strategy of formulating poorly soluble actives as liquid self-micro emulsifying drug delivery system (SMEDDS) has been explored in more than a thousand research papers. However, there have been a limited number of reports on pH sensitive solid SMEDDS. This study explored the feasibility of using poly (acrylic acid) modified mesoporous silica nanoparticles (MSNs-PAA) as a pH-mediated solid SMEDDS carrier for β-elemene. This SMEDDS was optimized using a central composite design-response surface methodology, pseudo ternary phase diagrams, and studies of the preliminary stability. MSNs-PAA was synthesized and used for loading β-elemene SMEDDS. Ele/MSNs-PAA was capable of pH-sensitive release of β-elemene. In addition to structural analyses, the morphological and stability of this SMEDDS was also investigated. In comparison of the β-elemene solution and the SMEDDS, the Ele/MSNs-PAA demonstrated improved Cmax, AUC and MRT after oral administration. These results suggested that the MSNs-PAA could be further developed as a promising approach for the pH sensitive release of β-elemene SMEDDS with enhanced oral bioavailability.

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.

Design and Evaluation of a Self-Emulsifying Drug Delivery System of Aripiprazole

The present investigation is aimed at enhancing the solubility and the dissolution rate of aripiprazole by formulating a self-micro emulsifying drug delivery system. The preliminary solubility screening of aripiprazole was determined in oils, surfactants and cosurfactants, respectively. Among those screened, isopropyl myristate, Tween 80 and propylene glycol showed good solubilizing efficiency and were selected for further formulations. A pseudoternary phase diagram was constructed at the ratios of 2:1, 3:1, 4:1 of oil to Smix (surfactant:Tween 80) and cosurfactant (propylene glycol) to find out the self-emulsification region. In vitro dissolution studies of the formulations were carried out in a simulated acidic buffer pH 2.2. A liquid self-micro emulsifying drug delivery system with an optimum composition was converted to solid formulation using crospovidone. Both solid and liquid formulations were evaluated for the cloud point and self-emulsification time. Differential scanning calorimetry endotherm provided confirmation for the amorphisation of the drug. Zeta potential and particle size analysis was carried out on the optimized formula. These studies revealed that the prepared self-micro emulsifying drug delivery system exhibited increased dissolution rate profile in comparison to the pure drug and marketed aripiprazole tablets.

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).