Self-microemulsifying Delivery System Research Articles

SMEDDS를 이용한 naproxen의 용출률 개선 및 in vivo 효능 평가

Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) administered to reduce pain, inflammation, and fever. The extended half-life of naproxen enables prolonged efficacy, leading to symptom relief and high patient satisfaction. However, naproxen has notably low solubility in water (15.9 mg/L). The present study aimed to enhance the solubility and dissolution rate of naproxen by using a self-microemulsifying delivery system (SMEDDS). Labrasol® was used as the primary oil and Labrafil® M1944 and Cremophor® RH-40 as the surfactants in the SMEDDS. The ratio of the selected oil to the surfactant was determined to identify the equilibrium range with good solubility. Subsequently, the efficacy was confirmed to be within the applicable range. The results indicated that the SMEDDS formulation showed higher dissolution rates than the salt-formulated purified naproxen product. Furthermore, the efficacy was compared with that of commercially available naproxen emulsion-filled soft gel capsules in an animal model of gastric ulcers, showing the excellent gastro-protective abilities of the naproxen SMEDDS. This study provides an appropriate oil and ratio for a naproxen SMEDDS, confirming it sefficacy, dissolution rate, and stability. These results will guide future directions in naproxen research and manufacturing.

Supersaturable Solid Self-microemulsifying Delivery Systems of Astaxanthin via Spray Drying: Effects of Polymers and Solid Carriers.

This study aimed to develop the solid astaxanthin-encapsulated self-microemulsifying delivery system (S-AST SMEDS) spray-dried particles and investigate the effect of materials in formulations on product characteristics. The optimized liquid AST SMEDS incorporated with a polymeric precipitation inhibitor (PI) was solidified with a solid carrier by spray drying. Physicochemical properties of S-AST SMEDS spray-dried powders including morphology, particle size and distribution, flowability, solid-state characters, moisture content, yield, loading capacity of AST, and reconstitution properties were examined. Polymeric PIs seemed to have an impact on particles' size, surface smoothness, and flowability while solid carriers had an effect on the particles' moisture content and droplet size of microemulsions obtained after reconstitution. The amount of AST encapsulated in S-SMEDS powder was influenced by both polymer and solid carriers. Dissolution and short-term stability of S-AST SMEDS were also studied. Our developed spray-dried solid SMEDS particles helped enhance AST dissolution rate.

Impact of Polymers as Precipitation Inhibitors on Physicochemical Properties of Spray-Dried Astaxanthin-Loaded Self-Microemulsifying Delivery Systems

Supersaturated astaxanthin (AST)-loaded self-microemulsifying delivery system (SMEDS) was developed and formulated with polymeric precipitation inhibitors (PPIs) to improve the dissolution profile of AST. Based on our preliminary in vitro polymer screening test, hydroxypropyl cellulose (HPC-L) and polyvinyl alcohol (PVA8/88) were selected as PPIs and studied further in this work. Microemulsions prepared from AST SMEDS (composed of AST, rice bran oil, Kolliphor® RH40, and Span® 20) were mixed with maltodextrin (MD) as a solid carrier and each PPI solution and then solidified using a spray drying technique. Particle size of spray-dried S-MD-HPC powder had larger circular equivalent (CE) diameter (14.69 ± 0.75 μm) than the other formula and showed particle agglomeration in SEM images. Spray-dried S-MD-PVA powder had 8.94 ± 0.37 μm CE diameter, and smooth surface of particles was observed. Amorphous phase transformation and chemical compatibility of both spray-dried powder formulations were detected by FT-IR, PXRD, and DSC. S-MD-HPC had marginally slower dissolution rate and release profile of AST compared to those of S-MD-PVA; however, both HPC and PVA polymers exhibited the ability for AST precipitation prevention and solubilization enhancement. Although AST degradation was caused by high temperature, physicochemical properties of the spray-dried AST SMEDS (S-MD-HPC and S-MD-PVA) powders after reconstitution were not significantly changed upon storage at 30°C/ RH 75%. This study illustrated a novel platform of spray-dried AST SMEDS in combination with HPC or PVA as a polymeric precipitation inhibitor for improvement of AST loading, solubility, and stability.

Preparation, optimization using a mixture design, and characterization of a novel astaxanthin-loaded rice bran oil self-microemulsifying delivery system formulation

This research aimed to develop a self-microemulsifying delivery system (SMEDS) to increase dissolution rate of astaxanthin (AST) using a design of experiment (DoE) approach for investigating the effect of components on the physicochemical properties of AST SMEDS formulation. By applying the mixture design, the optimal compositions of rice bran (RB) oil (oil; X1), Kolliphor® RH40 (surfactant; X2), and Span® 20 (cosurfactant; X3) were determined based on the preliminary screening studies. The optimization models were validated by comparing the regression coefficient (R2) of the predicted values to the experimentally measured ones. Based on the desirability function, the optimized AST SMEDS was composed of 33.67% rice bran oil, 34.70% Kolliphor® RH40, and 31.63% Span® 20 which contained AST concentration (Y1) of 0.04% in the formulation and yielded microemulsion droplet size (Y2) of 40.79 ± 3.11 nm. The experimentally measured values obtained from the optimized AST SMEDS were in accordance with its predicted values with relatively low prediction errors (< 2%). The validated models were investigated by the contour plots, three-dimensional surface plots, and main effect plots. It was found that surfactant and cosurfactant inversely affected on droplet size changes whereas all three components (oil, surfactant and cosurfactant) did not relatively impact AST solubilizing capacity. In vitro release of AST SMEDS was significantly increased more than 90% compared to the raw AST powder. The optimized AST SMEDS was successfully developed by the mixture design and could be economically effective to enhance dissolution of poorly water-soluble AST.

Supersaturable self-microemulsifying delivery systems: an approach to enhance oral bioavailability of benzimidazole anticancer drugs.

This study explored the design of supersaturable self-microemulsifying drug delivery systems (S-SMEDDS) to address poor solubility and oral bioavailability of a novel benzimidazole derivative anticancer drug (BI). Firstly, self-microemulsifying drug delivery systems SMEDDS made of Miglyol® 812, Kolliphor® RH40, Transcutol® HP, and ethanol were prepared and loaded with the BI drug. Upon dispersion, the systems formed neutrally charged droplets of around 20nm. However, drug precipitation was observed following incubation with simulated gastric fluid (pH 1.2). Aiming at reducing this precipitation and enhancing drug payload, supersaturable systems were then prepared by adding 1% hydroxypropyl cellulose as precipitation inhibitor. Supersaturable systems maintained a higher amount of drug in a supersaturated state in gastric medium compared with conventional formulations and were stable in simulated intestinal medium (pH 6.8). In vitro cell studies using Caco-2 cell line showed that these formulations reduced in a transient manner the transepithelial electrical resistance of the monolayers without toxicity. Accordingly, confocal images revealed that the systems accumulated at tight junctions after a 2h exposure. In vivo pharmacokinetic studies carried out following oral administration of BI-loaded S-SMEDDS, SMEDDS, and free drug to healthy mice showed that supersaturable systems promoted drug absorption compared with the other formulations. Overall, these data highlight the potential of using the supersaturable approach as an alternative to conventional SMEDDS for improving oral systemic absorption of lipophilic drugs.

Interaction among protein, daidzein and surfactants in the WPI-based daidzein self-micro emulsifying delivery system

Interaction among protein, daidzein and surfactants in the WPI-based daidzein self-micro emulsifying delivery system

Interaction among protein, daidzein and surfactants in the WPI-based daidzein self-microemulsifying delivery system.

The self-microemulsifying delivery system was fabricated by whey protein isolate (WPI), daidzein (Dai) and surfactants, the interaction of WPI, Dai and D-α-Tocopherol polyethylene glycol succinate (TPGS) was hereby studied in the absence or presence of Tween 20. The increase of surfactant concentration led to the decrease of the modulus and changes of protein interfacial conformation, which allowed the formation of a strong intermolecular network. The environment and structure of WPI and daidzein could be changed by TPGS, and the addition of Tween 20 could further enhance the interaction between the components by changing TPGS structure. With the increase of surfactants and oil phase, Ksv and Ka values of WPI-Dai increased first and then decreased. Therefore, the interaction between the components was also dependent on the WPI-surfactant ration. These findings provide a potential strategy for designing microemulsion food system based on the understanding of the interactions among individual composition of microemulsions.

Self-microemulsifying delivery system of WPI-Dai nanocomplex mixed with nonionic surfactant and its superiority in delivering daidzein

Daidzein (Dai) exhibits a variety of pharmacologic actions. However, the low solubility and high crystallinity limit the bioavailability of daidzein. Therefore, the self-microemulsion drug delivery system (SMEDDS) was introduced to increase the solubility of daidzein and avoid the first pass effect. Whey protein isolate (WPI) was added as a precipitation inhibitor to SMEDDS (WD-SMEDDS) to inhibit daidzein crystallization and improve system stability. The final formulation was TPGS and Tween 20 as mixed surfactants, PEG400 as cosurfactant and ethyl oleate as oil phase to prepare WD-SMEDDS. The stability studies revealed that mixed surfactants were superior to single, and remained stable for at least 3 months. WD-SMEDDS showed excellent dissolution behavior that more than 90% and 80% of daidzein was released in pH 6.8 and pH 1.2, respectively. Therefore, protein-based SMEDDS might be an effective strategy for the oral administration of Dai and would be a potential system to deliver hydrophobic bioactive compounds.

Self-microemulsifying delivery system for improving bioavailability of water insoluble drugs

Self-microemulsifying drug delivery system (SMEDDS) is a uniform and transparent solution consisting of oil phase, surfactant, co-surfactant, and a small amount of water. It could be orally administered under gastrointestinal peristalsis and spontaneously dispersed to form an oil-in-water microemulsion with typical particle sizes lower than 100 nm. The microemulsion forms a hydration layer that easily passes through the gastrointestinal wall, which increases the permeability to intestinal epithelial cells, thereby increasing the solubility of poorly soluble drugs and significantly improving bioavailability. This paper mainly introduces the main factors of improving bioavailability of microemulsion delivery system, the application of SMEDDS, and the characteristics of SMEDDS in vivo and in vitro. Finally, it summarizes the current prospects of SMEDDS in this field and the challenges ahead.

Development of Triptolide Self-Microemulsifying Drug Delivery System and Its Anti-tumor Effect on Gastric Cancer Xenografts.

Purpose: To develop a triptolide (TP) self-microemulsifying drug delivery system and to investigate its anti-tumor effect on human gastric cancer line MGC80-3 xenografts in nude mice.Methods: The medium chain triglyceride (MCT) was selected as oil phase; polyoxyethylene castor oil (EL) was selected as surfactant, and PEG-400 was selected as cosurfactant. The mass ratio of each phase was optimized by central composite design and response surface methodology to prepare TP-SMEDDS (self-microemulsifying drug delivery system). The quality of TP-SMEDDS was evaluated, and its inhibitory effect on tumor growth investigated in nude mice transplanted with MGC80-3 cells.Results: The final prescription process was defined as follows: MCT mass ratio: 25.3%; EL mass ratio: 49.6%; PEG-400 mass ratio: 25.1%. The prepared TP-SMEDDS was a transparent liquid with a clear appearance (the theoretical particle size: 31.168 nm). On transmission electron microscopy, the microemulsion particles were spherical in size and uniformly distributed without adhesions. The in vitro release experiment showed complete release of the prepared TP-SMEDDS in PBS solution in 6 h. In vivo antitumor activity showed its inhibitory effect in the xenograft model.Conclusion: The self-microemulsifying delivery system improved the oral bioavailability and the in vivo antitumor effect of TP.

Effects of a Self–micro-emulsifying Delivery System Formulation Versus a Standard ω-3 Acid Ethyl Ester Product on the Bioavailability of Eicosapentaenoic Acid and Docosahexaenoic Acid: A Study in Healthy Men and Women in a Fasted State

PurposeIntakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with several potential health benefits, but standard ethyl ester (EE) formulations of these ω-3 fatty acids require the co-ingestion of fat for adequate absorption. The objective of this research was to assess the relative bioavailability of EPA and DHA administered in a proprietary self–micro-emulsifying delivery system (SMEDS) formulation compared with EPA and DHA in a standard ω-3 acid EE product in healthy men and women in a fasted state. MethodsThis randomized crossover study investigated the bioavailability of 2 encapsulated formulations of EPA and DHA, a capsule containing 500 mg EPA + DHA administered in a SMEDS formulation (SMEDS treatment), and a capsule containing 840 mg EPA + DHA in a standard ω-3 acid EE formulation (EE treatment). Subjects consumed a single dose of their assigned capsule in a fasting state, and plasma was collected before and for 24 h after dosing. Subjects underwent a ≥14-day washout and were crossed over to the other treatment condition. Plasma concentrations of EPA, DHA, and EPA + DHA were assessed. FindingsTwenty-three subjects (11 women, 12 men; mean [SEM] age, 33.8 [2.1] years; and body mass index, 24.9 [0.7] kg/m2) completed the trial. The baseline-adjusted, dose-normalized, arithmetic means (SD) of the incremental (i)-AUC0–24h for EPA + DHA were 543 (266) and 102 (88.2) h · μg/mL/g for the SMEDS and EE formulations, respectively (P < 0.001). The iAUC0–24h least-squares geometric mean ratio (90% CI) for SMEDS:standard EE was 475/58 = 8.2 (4.8–13.9), indicating markedly higher bioavailability of EPA + DHA with the SMEDS formulation compared to the standard EE formulation. This finding was also true for EPA (geometric mean ratio [90% CI], 18.2 [11.3–29.3]) and DHA (geometric mean ratio [90% CI], 4.5 [2.9–7.0]). ImplicationsThe SMEDS delivery system markedly enhanced appearance in plasma of EPA and DHA, compared to a standard EE formulation, when ingested in the fasting state. ClinicalTrials.gov identifier: NCT03443076.

A Novel Self-Micro-Emulsifying Delivery System Enhances Enrichment of Eicosapentaenoic Acid and Docosahexaenoic Acid after Single and Repeated Dosing in Healthy Adults in a Randomized Trial

BackgroundA self-micro-emulsifying delivery system (SMEDS) promotes spontaneous emulsification of omega-3 (n–3) ethyl esters (EEs) into microdroplets in the stomach. ObjectiveThe objective was to compare the effect of SMEDS preparations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) EEs with standard EEs on EPA and DHA concentrations in the bloodstream after a single dose and repeated daily dosing. MethodsEighty healthy subjects aged 18–65 y were randomly assigned to SMEDS-EPA or EE-EPA (both providing more EPA than DHA) or SMEDS-DHA or EE-DHA (both providing more DHA than EPA). They consumed a single dose (1.23–1.33 g EPA+DHA) without a meal, and EPA and DHA were measured in plasma over the following 24 h. Participants continued to take a single dose each morning before breakfast for 12 wk. EPA and DHA were measured in fasting plasma, mononuclear cells (MNCs), and RBCs. ResultsEPA and DHA were higher in plasma in the 24 h after a single dose of SMEDS-EPA or SMEDS-DHA than after consuming the comparator EE (P < 0.001 for both). Compared with the EE form, repeated daily dosing of the SMEDS formulations for 12 wk resulted in higher concentrations of EPA and DHA in plasma (P = 0.086 and 0.005, respectively), MNCs (P < 0.001 and 0.020, respectively), and RBCs (both P < 0.001). The omega-3 index increased over 12 wk from 5.1 ± 0.9 to 7.9 ± 0.9 in the SMEDS-EPA group, from 5.3 ± 1.1 to 9.0 ± 1.2 in the SMEDS-DHA group, from 4.8 ± 0.8 to 6.4 ± 0.9 in the EE-EPA group, and from 5.2 ± 0.9 to 7.2 ± 1.0 in the EE-DHA group (all P < 0.001). The omega-3 index was higher with SMEDS than with the comparator EE at 12 wk (both P < 0.001). ConclusionCompared with standard EEs, a SMEDS results in greater incorporation of EPA and DHA into blood pools after a single dose and with repeated daily dosing in healthy adults. A SMEDS enhances delivery of bioactive ω-3 fatty acids. This trial was registered at www.isrctn.com as ISRCTN96459690.

Preparation and characterization of coenzyme Q10 loaded solid lipid-based formulations for enhancement of gastrointestinal solubilization

The aim of current research was to develop two types of solid lipid-based formulations to enhance solubility and stability of poorly water-soluble coenzyme Q10 (CoQ10). The powders of solid self-microemulsifying delivery system (SMEDS) were produced by rotational evaporation with magnesium aluminum silicate. And silica lipid hybrid (SLH) microparticles were developed by lyophilization of oil-in-water emulsions with Aerosil 300 silica nanoparticles as solid carrier. The in vitro dissolution experiment indicated that the dissolution behavior of solid SMEDS and SLH microparticles could be explained by Rigter-Peppas and Weibull model respectively. The in vitro lipolysis study revealed that compared with pure CoQ10, solid SMEDS and SLH microparticles significantly enhanced the solubility of CoQ10 in the aqueous medium under fasted and fed conditions. During a 30-day stability study, solid formulations showed good stability and high retention rate of CoQ10 (above 80%) after stored at three different temperatures. Besides, CoQ10 in solid formulations also exhibited good photostability. These results demonstrated that solid lipid-based formulations could be identified as appropriate strategies to improve solubility and stability of CoQ10.

Novel sulforaphane-enabled self-microemulsifying delivery systems (SFN-SMEDDS) of taxanes: Formulation development and in vitro cytotoxicity against breast cancer cells

Paclitaxel (PTX) and docetaxel (DTX) are highly effective chemotherapeutic agents against breast cancer cells. Existing PTX and DTX formulations, however, contain excipients that result in a multitude of side-effects. The objective of the present study was to develop novel self-microemulsifying formulations of PTX and DTX with significantly lower excipient content by utilizing the high solubility of taxanes in sulforaphane (SFN). SFN-enabled microemulsions were developed by a screening process in which optical microscopy and absorbance data were used to monitor the physical stability of the dispersions. Optimized formulations contained vitamin E TPGS and transcutol to aid in taxane dissolution in water and the formation of transparent microemulsions (< 20 nm). SFN microemulsions were stable in different dilution media and storage temperatures and had no hemolytic effect on RBCs. When tested in vitro against MDA-MB-231 and MCF7 cancer cells by IncuCyte® live cell analysis and CellTiter-Blue® assay, taxanes/SFN microemulsions showed similar activity as the commercial taxanes injection solutions. SFN was only found to potentiate the activity of taxanes when used at high concentrations. This study highlighted the unique properties of SFN and its potential use in reformulating taxanes with high drug load and significantly lower excipient content than the commercial products.

A novel self-micro-emulsifying delivery system (SMEDS) formulation significantly improves the fasting absorption of EPA and DHA from a single dose of an omega-3 ethyl ester concentrate

BackgroundAbsorption of EPA and DHA from Omega-3-acid ethyl ester (EE) concentrate supplements occurs most efficiently when taken in context of a fatty meal; adequate fat intake is required to release bile salts that emulsify and pancreatic enzymes that digest omega-3-containing lipids in the intestine. Current guidelines recommend reduction in fat intake and therefore there is a need to optimize the absorption of Omega-3 in those consuming low-fat or no-fat meals. To this end, BASF has developed an Absorption Acceleration Technology, a novel self-micro-emulsifying delivery system (SMEDS) formulation of highly concentrated Omega-3-acid EE which enables rapid emulsification and microdroplet formation upon entering the aqueous environment of the gut therefore enhances the absorption.MethodsTwo separate single dose, crossover studies were conducted to determine the relative bioavailability of omega-3-acid EE concentrate, either as a novel SMEDS formulation (PRF-021) or as control, in healthy fasted male and female adults at two dose levels (Study 1 “low dose”: 630 mg EPA + DHA in PRF-021 vs. 840 mg EPA + DHA in control; Study 2 “high dose”: 1680 mg EPA + DHA in PRF-021 vs. 3360 mg EPA + DHA in control). Blood samples were collected immediately before supplementation and at defined time intervals for 48 h. Plasma concentration of total EPA and DHA were determined for pharmacokinetic analysis, area under the curve (AUC) and maximum observed concentration (Cmax) was determined.ResultsTotal EPA plus DHA absorption from SMEDS formulation PRF-021 were 6.4 and 11.5 times higher compared to control in low- and high-dose studies respectively, determined as the ratio of baseline corrected, dose normalized AUC0-24h of PRF-021 over that of control. EPA and DHA individually showed differing levels of enhancement: the AUC0-24h ratio for EPA was 23.8 and 25.7 in low and high dose studies, respectively, and the AUC0-24h ratio for DHA was 3.6 and 5.6 in low and high dose studies, respectively. Cmax was also increased for both EPA and DHA 2.7- to 9.2-fold.ConclusionPRF-021 is a novel SMEDS formulation of Omega-3-acid EE demonstrating a marked improvement in absorption of a single dose of EPA and DHA EE under fasted conditions. This allows adequate absorption of Omega-3 from the supplement without the requirement of a high-fat meal.

Predicting solubilisation features of ternary phase diagrams of fully dilutable lecithin linker microemulsions

Fully dilutable microemulsions (μEs), used to design self-microemulsifying delivery system (SMEDS), are formulated as concentrate solutions containing oil and surfactants, without water. As water is added to dilute these systems, various μEs are produced (water-swollen reverse micelles, bicontinuous systems, and oil-swollen micelles), without the onset of phase separation. Currently, the formulation dilutable μEs follows a trial and error approach that has had a limited success. The objective of this work is to introduce the use of the hydrophilic-lipophilic-difference (HLD) and net-average-curvature (NAC) frameworks to predict the solubilisation features of ternary phase diagrams of lecithin-linker μEs and the use of these predictions to guide the formulation of dilutable μEs. To this end, the characteristic curvatures (Cc) of soybean lecithin (surfactant), glycerol monooleate (lipophilic linker) and polyglycerol caprylate (hydrophilic linker) and the equivalent alkane carbon number (EACN) of ethyl caprate (oil) were obtained via phase scans with reference surfactant-oil systems. These parameters were then used to calculate the HLD of lecithin-linkers-ethyl caprate microemulsions. The calculated HLDs were able to predict the phase transitions observed in the phase scans. The NAC was then used to fit and predict phase volumes obtained from salinity phase scans, and to predict the solubilisation features of ternary phase diagrams of the lecithin-linker formulations. The HLD-NAC predictions were reasonably accurate, and indicated that the largest region for dilutable μEs was obtained with slightly negative HLD values. The NAC framework also predicted, and explained, the changes in microemulsion properties along dilution lines.

Development of solidified self-microemulsifying delivery systems with enhanced stability of sirolimus and extended release

The application of sirolimus (SRL) as immunosuppressive agent is hampered by its poor water solubility and narrow therapeutic range. The self-microemulsifying drug delivery system (SMEDDS) succeeded in improving the solubility of SRL in our previous work. In this study, the formulation of the SMEDDS was further optimized by investigating the influence of the excipients including the media, antioxidant and organic acid. It was demonstrated that addition of 0.20% of citric acid in SMEDDS most efficiently promoted the stability of SRL under high temperature (40±2°C), high humidity (relative humidity 90±5%) or strong light irradiation (4500±500lx). SMEDDS absorbed by microcrystalline cellulose (MCC) was mixed with hydroxypropyl methylcellulose (HPMC) to prepare tablets. The optimal formulation composed of 15% of HPMC 100 LV with hardness of 120N, which had a sustained release of 12h. Results of X-ray powder diffraction and differential scanning calorimetry demonstrated that SRL in the tablets was in amorphous or molecularly dispersed state. The SMEDDS-tablets presented as promising substrates for water insoluble drugs with enhanced stability and extended release.

Preparation and evaluation of valsartan by a novel semi-solid self-microemulsifying delivery system using Gelucire 44/14

The aim of the present study was to develop a novel semi-solid self-microemulsifying drug delivery system (SMEDDS) using Gelucire® 44/14 as oil with strong solid character to improve the oral bioavailability of poorly soluble drug valsartan. The solubility of valsartan in various excipients was determined, the pseudo-ternary phase diagram was constructed in order to screen the optimal excipients, and DSC analysis was performed to evaluate the melting point of SMEDDS. The optimal drug-loaded SMEDDS formulation was consisted of 30% Gelucire® 44/14 (oil), 40% Solutol® HS 15 (surfactant), and 30% Transcutol® P (cosurfactant) (w/w) with 80 mg valsartan/g excipients. The average droplet sizes of the optimized blank and drug-loaded SMEDDS formulations were 26.20 ± 1.43 and 33.34 ± 2.15 nm, and the melting points of them were 35.6 and 36.8 °C, respectively. The in vitro dissolution rate of optimal semi-solid SMEDDS was increased compared with commercial capsules, resulting in the 2.72-fold and 2.97-fold enhancement of Cmax and AUC0–t after oral administration in rats, respectively. These results indicated that the novel semi-solid SMEDDS formulation could potentially improve the oral bioavailability of valsartan, and the semi-solid SMEDDS was a desirable system than the traditional liquid SMEDDS because it was convenient for preparation, storage and transportation due to semi-solid state at room temperature and melted state at body temperature.

Impact of Solidification on the Performance of Lipid-based Colloidal Carriers: Oil-based versus Self-emulsifying Systems

The study aims to develop and optimise lipid-based colloidal carriers (LBCC) for enhancing solubilisation and reducing fed/fasted variation for the poorly water-soluble danazol (DAN). Oil-based and self-microemulsifying delivery systems (SMEDDS) were developed, and the effect of solidification was investigated. Liquid SMEDDS (L-SMEDDS, Capmul MCM:Tween 80:Transcutol HP 1:2:1, w/w) and emulsion (Capmul MCM:soya lecithin 100:0.6, w/w) were developed. Solid-state formulations were prepared via (i) physical adsorption of L-SMEDDS (P-SMEDDS) or (ii) spray drying of emulsion (silica-lipid hybrid, SLH) and L-SMEDDS (spray-dried SMEDDS, S-SMEDDS) using Aerosil 380 silica nanoparticles as the solid carrier. In vitro lipid digestion and drug solubilisation under simulated intestinal conditions in both fasted and fed states were investigated. Solubilisation of unformulated DAN under both fasted and fed conditions was low, and a large fed/fasted variation was observed, i.e. 6.6-fold difference. All LBCC formulations provided enhanced drug solubilisation and significantly reduced the fed/fasted variation. For self-emulsifying LBCC, the fasted state drug solubilisation was ranked as L-SMEDDS > PSMEDDS > S-SMEDDS, suggesting that solidification reduced the capability of SMEDDS in presenting DAN to the aqueous phase. However, in the case of oil-based LBCC, improved drug solubility was observed with the solid form SLH under both fasted and fed state in comparison to that of the equivalent liquid form. Overall, the SLH, which provided the highest drug solubilisation in the fasted state (i.e. 10-fold higher than the pure DAN) and the smallest fed/fasted variation, was considered an optimised solid LBCC to enhance the solubilisation of DAN and reduce the fed/fasted variation.

Formulation and Physicochemical Characterisation of a Novel Self-Microemulsifying Delivery System as Hydrotropic and Solubilising Agent for Penfluridol

As a poorly water-soluble chemical, penfluridol is used as a maintenance drug for individuals with chronic schizophrenia. A novel self-microemulsifying drug delivery system has been successfully developed to benefit the solubility of penfluridol. Pseudo-ternary phase diagrams were constructed to investigate the phase behaviour and to assess the effects of different co-surfactants and the mass ratios of surfactant to co-surfactant (Km) on the phase regions. Optimal compositions of the formed systems were screened via viscosity studies and microemulsion droplet size tests. The optimal formulation of penfluridol-loaded self-microemulsion consists of penfluridol 5.0%, oil (MCT) 15.8%, surfactant (cremophor EL) 52.8%, co-surfactant (PEG-400) 26.4%, with the average particle size at approximately (53.5±4.3) nm. Transmission electron microscopy (TEM) revealed the spherical nature and size homogeneity of the microemulsion droplets. No significant variations (droplet sizes and penfluridol contents) in microemulsion were observed over a period of 30 days at 4°C and 25°C, respectively. The developed self-microemulsion proved to be a potential candidate to enhance the solubility of penfluridol.