Self-emulsifying Properties Research Articles

Physico-chemical Characterisation of Self-Emulsifying Microemulsion of Antimalarial.

Emulsions are employed as drug carriers in pharmaceutical formulations, particularly because they can increase the oral bioavailability of poorly absorbed medications.1 One of the most often used techniques to improve the oral bioavailability of medications, particularly anti-malarial ones, is the use of lipid-based drug delivery. The current research study focuses on using the lipid-based formulation strategy, i.e., self-emulsifying micro emulsions to formulate such anti-malarial drugs and characterise them to study their stability so that the possibility of bioavailability can be studied more. The current research emphasizes on characterisation techniques like transmission electron microscopy (TEM), turbidity index (%TI) and globule size determination as simpler and industrially implacable techniques to study the stability of the self-emulsifying properties of such formulations. In-order to obtain stable formulations with self-emulsifying behaviour the most important factors like the concentrations of surfactants and co-surfactants were one of the variables which were varied in-order to observe their effect on the overall stability of the microemulsions. This research is a step towards the usage of self-emulsifying microemulsions of anti-malarial drugs, for enhancement of oral bioavailability and encourages other researches to use this formulation strategy to improve bioavailability.

Development and in vitro evaluation of an infant friendly self-nanoemulsifying drug delivery system (SNEDDS) loaded with an amphotericin B-monoacyl phosphatidylcholine complex for oral delivery

Until relatively recently, the pediatric population has largely been ignored during the development of new drug products, which has led to a high level of “off-label” use of drugs in this particular population. In this study, an infant friendly self-nanoemulsifying drug delivery system (SNEDDS) was developed for oral delivery of a commonly used “off-label” drug – amphotericin B (AmB). AmB was complexed with monoacyl-phosphatidylcholine (MAPC) by lyophilization, transforming crystalline AmB into its amorphous state in the AmB-MAPC complex (APC). The APC-loaded SNEDDS (APC-SNEDDS) showed excellent self-emulsifying properties; after dispersion of the APC-SNEDDS in purified water, nanoscale emulsion droplets were formed within 1 min with a z-average size of 179 ± 1 nm. In vitro pediatric gastrointestinal (GI) digestion and dissolution results showed that the APC-SNEDDS significantly increased the amount of AmB solubilized in aqueous phase and that the precipitated AmB from the APC-SNEDDS re-dissolved faster, compared with crystalline AmB in SNEDDS (AmB-SNEDDS), the complex without the SNEDDS (APC), the physical mixture of AmB and MAPC (AmB/MAPC PM), and crystalline AmB alone (AmB). Overall, the present in vitro results suggest that integrating the APC into an infant friendly SNEDDS is a promising approach for oral delivery of AmB to young pediatric patients.

Formulation Development of Solid Self-Nanoemulsifying Drug Delivery Systems of Quetiapine Fumarate via Hot-Melt Extrusion Technology: Optimization Using Central Composite Design.

Quetiapine fumarate (QTF) was approved for the treatment of schizophrenia and acute manic episodes. QTF can also be used as an adjunctive treatment for major depressive disorders. QTF oral bioavailability is limited due to its poor aqueous solubility and pre-systemic metabolism. The objective of the current investigation was the formulation development and manufacturing of solid self-nanoemulsifying drug delivery system (S-SNEDDS) formulation through a single-step continuous hot-melt extrusion (HME) process to address these drawbacks. In this study, Capmul® MCM, Gelucire® 48/16, and propylene glycol were selected as oil, surfactant, and co-surfactant, respectively, for the preparation of S-SNEDDS. Soluplus® and Klucel™ EF (1:1) were selected as the solid carrier. Response surface methodology in the form of central composite design (CCD) was utilized in the current experimental design to develop the S-SNEDDS formulations via a continuous HME technology. The developed formulations were evaluated for self-emulsifying properties, particle size distribution, thermal behavior, crystallinity, morphology, physicochemical incompatibility, accelerated stability, and in vitro drug release studies. The globule size and emulsification time of the optimized SNEDDS formulation was 92.27 ± 3.4 nm and 3.4 ± 3.38 min. The differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) studies revealed the amorphous nature of the drug within the formulation. There were no drug-excipient incompatibilities observed following the Fourier transform infrared (FTIR) spectroscopy. The optimized formulation showed an extended-release profile for 24 h. The optimized formulation was stable for three months (last time-point tested) at 40 °C/75% RH. Therefore, the developed S-SNEDDS formulation could be an effective oral delivery platform for QTF and could lead to better therapeutic outcomes.

Analysis of the Physical Characteristics of an Anhydrous Vehicle for Compounded Pediatric Oral Liquids.

The paucity of suitable drug formulations for pediatric patients generates a need for customized, compounded medications. This research study was set out to comprehensively analyze the physical properties of the new, proprietary anhydrous oral vehicle SuspendIt® Anhydrous, which was designed for compounding pediatric oral liquids. A wide range of tests was used, including sedimentation volume, viscosity, droplet size after dispersion in simulated gastric fluid, microscopic examination and content uniformity measurements to evaluate the properties of the anhydrous vehicle. The results showed that the vehicle exhibited consistent physical properties under varying conditions and maintained stability over time. This can be attributed to the unique blend of excipients in its formulation, which not only maintain its viscosity but also confer thixotropic behavior. The unique combination of viscous, thixotropic and self-emulsifying properties allows for rapid redispersibility, sedimentation stability, accurate dosing, potential drug solubility, dispersion and promotion of enhanced gastrointestinal distribution and absorption. Furthermore, the vehicle demonstrated long-term sedimentation stability and content uniformity for a list of 13 anhydrous suspensions. These results suggest that the anhydrous oral vehicle could serve as a versatile base for pediatric formulation, potentially filling an important gap in pediatric drug delivery. Future studies can further investigate its compatibility, stability and performance with other drugs and in different clinical scenarios.

Quality by Design-Based Development of Solid Self-Emulsifying Drug Delivery System (SEDDS) as a Potential Carrier for Oral Delivery of Lysozyme.

For many years, researchers have been making efforts to find a manufacturing technique, as well as a drug delivery system, that will allow for oral delivery of biopharmaceuticals to their target site of action without impairing their biological activity. Due to the positive in vivo outcomes of this formulation strategy, self-emulsifying drug delivery systems (SEDDSs) have been intensively studied in the last few years as a way of overcoming the different challenges associated with the oral delivery of macromolecules. The purpose of the present study was to examine the possibility of developing solid SEDDSs as potential carriers for the oral delivery of lysozyme (LYS) using the Quality by Design (QbD) concept. LYS was successfully ion paired with anionic surfactant, sodium dodecyl sulphate (SDS), and this complex was incorporated into a previously developed and optimized liquid SEDDS formulation comprising medium-chain triglycerides, polysorbate 80, and PEG 400. The final formulation of a liquid SEDDS carrying the LYS:SDS complex showed satisfactory in vitro characteristics as well as self-emulsifying properties (droplet size: 13.02 nm, PDI: 0.245, and zeta potential: -4.85 mV). The obtained nanoemulsions were robust to dilution in the different media and highly stable after 7 days, with a minor increase in droplet size (13.84 nm) and constant negative zeta potential (-0.49 mV). An optimized liquid SEDDS loaded with the LYS:SDS complex was further solidified into powders by adsorption onto a chosen solid carrier, followed by direct compression into self-emulsifying tablets. Solid SEDDS formulations also exhibited acceptable in vitro characteristics, while LYS preserved its therapeutic activity in all phases of the development process. On the basis of the results gathered, loading the hydrophobic ion pairs of therapeutic proteins and peptides to solid SEDDS may serve as a potential method for delivering biopharmaceuticals orally.

Hemicellulose β-ketoester prepared by reaction with alkyl ketene dimer and its self-emulsifying properties

To make use of the byproduct in dissolving pulp production, hemicellulose collected from waste water was used to modify alkyl ketene dimer (AKD), confirmed by FT-IR and NMR analysis. The obtained product ACMHC exhibited self-emulsifying in absence of extra surfactant when emulsion was prepared. The obtained ACMHC emulsion (10 %) showed small droplet diameter of 0.8 µm and high zeta potential of − 40 mV. The effects of ionic strength, pH, temperature and long-term storage on properties of the emulsion were investigated. In emulsification long alkyl groups from AKD formed the core while hemicellulose formed the shell. Due to electrostatic repulsion and steric repulsion from the shell, ACMHC emulsion stayed stable. Furthermore, ACMHC emulsion was applied on paper to evaluate its influence on barrier properties. Oil barrier grade of the coated paper was increased from 0/12 to 5/12 and water contact angle reached 108.5° at a coating amount of 6.11 g/m2. These results demonstrated self-emulsifying AKD emulsion could be achieved by combining hemicellulose and AKD and the resultant emulsion could potentially serve as coatings for paper materials for enhancing barrier properties.

3D Printed Tacrolimus Rectal Formulations Ameliorate Colitis in an Experimental Animal Model of Inflammatory Bowel Disease.

The aim of this study was to fabricate novel self-supporting tacrolimus suppositories using semisolid extrusion 3-dimensional printing (3DP) and to investigate their efficacy in an experimental model of inflammatory bowel disease. Blends of Gelucire 44/14 and coconut oil were employed as lipid excipients to obtain suppository formulations with self-emulsifying properties, which were then tested in a TNBS (2,4,6-trinitrobenzenesulfonic acid) induced rat colitis model. Disease activity was monitored using PET/CT medical imaging; maximum standardized uptake values (SUVmax), a measure of tissue radiotracer accumulation rate, together with body weight changes and histological assessments, were used as inflammatory indices to monitor treatment efficacy. Following tacrolimus treatment, a significant reduction in SUVmax was observed on days 7 and 10 in the rat colon sections compared to non-treated animals. Histological analysis using Nancy index confirmed disease remission. Moreover, statistical analysis showed a positive correlation (R2 = 71.48%) between SUVmax values and weight changes over time. Overall, this study demonstrates the effectiveness of 3D printed tacrolimus suppositories to ameliorate colitis and highlights the utility of non-invasive PET/CT imaging to evaluate new therapies in the preclinical area.

Cellular uptake of self-emulsifying drug-delivery systems: polyethylene glycol versus polyglycerol surface.

Aim: Comparison of the impact of polyethylene glycol (PEG) and polyglycerol (PG) surface decoration on self-emulsifying drug delivery system (SEDDS)-membrane interaction and cellular uptake. Materials &methods: PEG-, PEG/PG- and PG-SEDDS were assessed regarding their self-emulsifying properties, surface charge, bile salt fusibility, cellular uptake and interaction with endosome-mimicking membranes. Results: SEDDS exhibited droplet sizes between 150 and175nm, a narrow size distribution and self-emulsified within 7min. Higher PEG-surfactant amounts in SEDDS resulted in charge-shielding and thus in a decrease of ζ potential up to Δ11mV. The inert PEG-surface hampered bile salt fusion and interfered SEDDS-cell interaction. By reducing the PEG-surfactant amount to 10%, cellular uptake increased twofold compared with PEG-SEDDS containing 40% PEG-surfactant. PG-SEDDS containing no PEG-surfactants showed a threefold increased cellular uptake. Furthermore, complete replacement of PEG-surfactants by PG-surfactants led to enhanced cellular interaction and improved disruption endosome-like membranes. Conclusion:PG-surfactants demonstrated high potential to address PEG-surface associated drawbacks in SEDDS.

Bioactive Self-Nanoemulsifying Drug Delivery Systems (Bio-SNEDDS) for Combined Oral Delivery of Curcumin and Piperine.

Background: Bioactive oils of natural origin have gained huge interests from health care professionals and patients. Objective: To design a bioactive self-nanoemulsifying drug delivery system (Bio-SNEDDS) comprising curcumin (CUR) and piperine (PP) by incorporating bioactive natural oils in the formulation. Methods: The self-emulsifying properties of apricot, avocado, black seed and Zanthoxylum rhetsa seed oils were screened within various SNEDDS formulations. Each liquid SNEDDS formulation was loaded with both CUR and PP. The optimal liquid SNEDDS were solidified using Aeroperl® and Neusilin® at 1:1 w/w ratio. Liquid and solid SNEDDS were characterized by droplet size analysis, equilibrium solubility, scanning electron microscopy, X-ray powder diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy. In-vitro dissolution studies were performed to evaluate the efficiency of CUR and PP release from solid Bio-SNEDDS. Results: The liquid SNEDDS comprised of black seed oil exhibited excellent self-emulsification performance, low droplet size along with transparent appearance. The inclusion of the cosolvent Transcutol P improved the solubilization capacity of both CUR and PP. The liquid SNEDDS were efficiently solidified using the two adsorbents and presented the drugs within amorphous state. In particular, SNEDDS comprised of black seed oil/Imwitor988/Transcutol P/Cremophor RH40 (20/20/10/50) and when solidified with Neusilin showed enhanced CUR and PP release (up to 60% and 77%, respectively). In addition, this formulation efficiently delivers the highly bioactive black seed oil to the patient. Conclusions: The optimized Bio-SNEDDS comprising black seed oil showed outstanding self-emulsification characteristics along with enhanced CUR/PP dissolution upon solidification.

PTS micelles for the delivery of hydrophobic methotrexate

Polyoxyethanyl-α-tocopheryl sebacate (PTS) is an amphiphilic compound with self-emulsifying properties known to form micelles. In this work, we report the production of PTS micelles for the encapsulation and delivery of a hydrophobic derivative of methotrexate, MTX di-ethylated (MTX-OEt). We optimized the micelles production by testing two different techniques: auxiliary solvent and sonication. Small and homogeneous micelles (≈40 nm) were obtained through the auxiliary solvent method performed at 30 °C and using 15 mg/mL of PTS. The produced micelles with the most promising physicochemical properties did not induce cytotoxicity when tested in normal human cells (BJ5ta cells), being considered for the encapsulation of MTX-OEt. This prodrug was achieved by Fisher esterification using ethanol, being isolated in good yield (η = 68%). MTX-OEt was efficiently encapsulated onto the produced micelles which preserved their physicochemical properties. The PTS micelles loaded with MTX-OEt, free MTX-OEt and free unmodified MTX revealed similar biological effect against cancer cells (Caco-2 cells). These results demonstrated that the biological activity of MTX is not altered after modification. The developed PTS micelles revealed a promising intracellular delivery performance with potentiality for cancer therapy.

Self-emulsifying Pellets Prepared by Extrusion/Spheronization: In vitro/In vivo Evaluation.

The purpose of the current study was to investigate the feasibility of producing solid self-emulsifying pellets using the extrusion/spheronization technique with an aim to increase the bioavailability of selected drug and also to encounter the problems associated with liquid lipid formulations. Selfemulsifying formulations are experiencing a very active development as reflected by the numerous publications and patents being granted on these systems. The patents on self-emulsifying formulation (US20036630150) and (US20006054136) helped in selecting the drug and excipients. These pellets were prepared using liquid SNEDDS (24.59 % LBF M 2125 CS + Maisine35-1; 1:1 ratio) (oil), 50.27 % Labrasol (surfactant) and 25.13% Lauroglycol 90 (cosurfactant), adsorbent (silicon dioxide), pellet forming excipient (microcrystalline cellulose), binder (pregelatinized starch), disintegrant (croscarmelose sodium) and lubricant (corn starch). The resulting self-emulsified pellets loaded with about 32% liquid SNEDDS exhibited uniform pellet size and round shape, droplet size distribution following self-emulsification was nearly same to the liquid SNEDDS (26.5 nm and 24.8 nm, respectively). The in vitro release was significantly higher than the plain drug (p<0.01). AUC0-36h of sertraline from the pellets showed about 5-fold greater than the plain drug and no significant difference compared with the liquid SNEDDS (p>0.05). In conclusion, spherical pellets with low friability and self-emulsifying properties can be produced by the standard extrusion/spheronization technique. The pellets are capable of transferring lipophilic compounds into the aqueous phase and have a high potential to increase the oral absorption of lipophilic drugs.

Production of a bioactive lipid-based delivery system from ratfish liver oil by enzymatic glycerolysis

This work shows, for the first time, the enzymatic glycerolysis of ratfish liver oil (RLO) as a method to obtain bioactive lipid carriers with potential self-emulsifying properties. Reaction conditions, leading to a 34% (w/w) of monoacylglycerol, were attained using 67% (w/w) of cyclopentanone as solvent, 40°C, a molar ratio RLO to glycerol of 1:1 in the presence of Novozyme 435. Then, the glycerolysis process was scaled-up at pilot plant, with similar results to those obtained at laboratory scale. Finally, the effect of the enzymatic glycerolysis on the oxidative quality of ratfish liver oil was also evaluated determining peroxide, p-anisidine and TOTOX values along the different stages of the bioprocess. Results showed no deleterious effect of the glycerolysis process on the oil oxidative quality. Therefore, in the present work, an efficient, cost-effective, environmental friendly and easily scalable process of enzymatic glycerolysis has been developed to design a bioactive lipid-based delivery system from ratfish liver oil with potential application in the formulation of highly bioavailable and bioefficient nutritional supplements and functional foods.

A Self-Microemulsifying Drug Delivery System to Overcome Intestinal Resveratrol Toxicity and Presystemic Metabolism

A mixed lipid-mixed surfactant self-microemulsifying drug delivery system (SMEDDS) was developed to exploit the health benefits of resveratrol, a Biopharmaceutical Classification System Class 2 natural polyphenol, subject to extensive intestinal presystemic metabolism. SMEDDS with a mixed lipid phase (castor oil/Capmul MCM 1:1) and a mixed surfactant phase (Kolliphor EL/Kolliphor RH 40 1:1) was developed and evaluated for its self-emulsifying properties and in vitro dispersion. The impact of SMEDDS on the permeability properties of resveratrol and its metabolite fluxes through the rat intestine and Caco-2 cells was monitored. The inhibitory effect of selected SMEDDS components on the efflux transporters multidrug resistance-associated protein and P-gp as well as cytotoxicity was assessed on Caco-2 cells. The formulation allowed for high resveratrol loading (122.5 mg/g SMEDDS), excellent self-emulsifying properties, and very rapid release. When formulated in SMEDDS, resveratrol metabolite efflux significantly declined. The formulation (SMEDDS without incorporated resveratrol) and its individual components did not compromise in vitro cell vitality and integrity. Mixed lipid-mixed surfactant SMEDDS is a prospective formulation to improve resveratrol biopharmaceutical, pharmacokinetic, and toxicological properties, leading the way to resveratrol use not only as a supplement but also as a pharmacological drug.

Self-Nanoemulsifying Drug Delivery System of Nifedipine: Impact of Hydrophilic–Lipophilic Balance and Molecular Structure of Mixed Surfactants

A simple but novel mixed surfactant system was designed to fabricate a self-nanoemulsifying drug delivery system (SNEDDS) based on hydrophilic-lipophilic balance (HLB) value. The impacts of HLB and molecular structure of surfactants on the formation of SNEDDS were investigated. After screening various oils and surfactants, nifedipine (NDP)-loaded liquid SNEDDS was formulated with Imwitor(®) 742 as oil and Tween(®)/Span(®) or Cremophor(®)/Span(®) as mixed surfactant. Droplet size of the emulsions obtained after dispersing SNEDDS containing Tween(®)/Span(®) in aqueous medium was independent of the HLB of a mixed surfactant. The use of the Cremophor(®)/Span(®) blend gave nanosized emulsion at higher HLB. The structure of the surfactant was found to influence the emulsion droplet size. Solid SNEDDS was then prepared by adsorbing NDP-loaded liquid SNEDDS comprising Cremophor(®) RH40/Span(®) 80 onto Aerosil(®) 200 or Aerosil(®) R972 as inert solid carrier. Solid SNEDDS formulations using higher amounts (30-50% w/w) of Aerosil(®) 200 exhibited good flow properties with smooth surface and preserved the self-emulsifying properties of liquid SNEDDS. Differential scanning calorimetry and X-ray diffraction studies of solid SNEDDS revealed the transformation of the crystalline structure of NDP due to its molecular dispersion state. In vitro dissolution study demonstrated higher dissolution of NDP from solid SNEDDS compared with NDP powder.

Development and physicochemical characterization of saquinavir mesylate solid dispersions using Gelucire 44/14 or PEG 4000 as carrier

Solid dispersions of saquinavir mesylate containing either Gelucire® 44/14 or poly(ethylene glycol) (PEG) 4000, or mixtures of each carrier with Tween 80 or polyvinyl pyrrolidone (PVP) K30 were prepared in order to enhance the drug dissolution rate. These systems were prepared by the melting method and characterized by X-ray powder diffraction, microscopical techniques, and Raman spectroscopy aiming to establish a relationship between physicochemical and dissolution properties under different cooling conditions. Modifications in degree of crystalline order/disorder over time were observed in preparations with both carriers. Overall, formulations cooled and stored at -20 °C showed less variation in dissolution rates than those at 25 °C. Although Tween 80 has enhanced the known self-emulsifying properties of Gelucire® 44/14, its combination with PEG 4000 displayed miscibility problems. The addition of PVP K30 was not the most effective approach in enhancing the dissolution in early steps; however, the drug dissolution was stable after 7 days of storage at 25 °C. The combination of PEG 4000 and PVP K30 maintained the dissolution properties for 60 and 90 days at 25 °C/95% relative humidity and 40 °C/75% (f₂ values >50), respectively.

Self-nanoemulsifying drug delivery system of cefpodoxime proxetil containing tocopherol polyethylene glycol succinate

Context: Lipid based drug delivery systems have gained prominence in last decade for drugs with dissolution rate limited oral bioavailability.Objective: To improve the solubility, permeability and oral bioavailability of cefpodoxime proxetil, β-lactam antibiotic. It is BCS Class IV drug having solubility 400 µg/mL and 50% oral bioavailability.Materials and methods: Self-nanoemulsifying drug delivery system (SNEDDS) using various surfactant and cosurfactants such as tween 80, tocopheryl polyethylene glycol succinate (TPGS), propylene glycol and Capmul MCM as oil phase were prepared. Ternary phase diagrams were constructed to identify stable microemulsion region. Percent transmittance studies helped to shortlist the surfactant–cosurfactant combination.Results and discussion: Tween 80 and TPGS as surfactants and Capmul MCM as oil phase were found to produce stable nanoemulsions. Five formulations of SNEDDS had globule size of 55–60 nm and zeta potential of −4 to −11 mV. Self-emulsification time was between 221 and 370 s, while viscosity was dependent on composition of SNEDDS. Cloud point was above 70°C which indicated the retention of in vivo self-emulsifying properties. Average flux for cefpodoxime proxetil (CP) and SNEDDS was 0.104 and 0.985 µg/cm2 min. Permeability was 19.72 and 206 for CP and SNEDDS. Liquid SNEDDS spray coated onto micropellets of microcrystalline cellulose (18–20#) were analysed by scanning electron microscope (SEM), self-emulsification and in vitro dissolution. A 5.36-fold increase in area under curve AUC0–∞ was observed for CP-SNEDDS than plain drug. Minimum inhibitory concentration (MIC) was lower for SNEDDS. Liquid and SNEDDS micropellets were stable under accelerated conditions.Conclusion: SNEDDS formulations led to improved oral bioavailability due to enhanced solubilization of selected drug.

A Comparison of the Self‐emulsifying Properties of Polyglycolysed Glyceride Oils

The self-emulsifying properties of three glyceride-based oils (Labrafac CM10, Labrafil WL2609 BS and Labrafil M1944 CS) mixed with Tween 20 have been investigated using visual examination, particle size analysis and differential interference contrast microscopy. It was found that the oil with the highest hydrophilic-lipophilic balance (HLB) value (Labrafac CM 10, HLB 10) showed the greatest tendency to spontaneously self-emulsify and yielded emulsions with the smallest particle size. Examination using differential interference contrast microscopy indicated that the oil-surfactant mixes may form w/o/w emulsions in water on gentle agitation, particularly when using Labrafil M1944 CS which had the lowest HLB of the three oils (HLB 3–4). The results therefore indicate firstly that the nature of the oil may have a profound effect on the self-emulsification, secondly that these systems may form multiple emulsions and thirdly that the requirements to self-emulsify and to form w/o/w emulsions appear to be contrasting.

Solid Self-Microemulsifying Formulation for Candesartan Cilexetil

Sparingly, water-soluble drugs such as candesartan cilexetil offer challenges in developing a drug product with adequate bioavailability. The objective of the present study was to develop and characterize self-microemulsifying drug delivery system (SMEDDS) of candesartan cilexetil for filling into hard gelatin capsules. Solubility of candesartan cilexetil was evaluated in various nonaqueous careers that included oils, surfactants, and cosurfactants. Pseudoternary phase diagrams were constructed to identify the self-microemulsification region. Four self-microemulsifying formulations were prepared using mixtures of oils, surfactants, and cosurfactants in various proportions. The self-microemulsification properties, droplet size, and zeta potential of these formulations were studied upon dilution with water. The optimized liquid SMEDDS formulation was converted into free flowing powder by adsorbing onto a solid carrier for encapsulation. The dissolution characteristics of solid intermediates of SMEDDS filled into hard gelatin capsules was investigated and compared with liquid formulation and commercial formulation to ascertain the impact on self-emulsifying properties following conversion. The results indicated that solid intermediates showed comparable rate and extent of drug dissolution in a discriminating dissolution medium as liquid SMEDDS indicating that the self-emulsifying properties of SMEDDS were unaffected following conversion. Also, the rate and extent of drug dissolution for solid intermediates was significantly higher than commercial tablet formulation. The results from this study demonstrate the potential use of SMEDDS as a means of improving solubility, dissolution, and concomitantly the bioavailability.

A new self-emulsifying drug delivery system (SEDDS) for poorly soluble drugs: Characterization, dissolution, in vitro digestion and incorporation into solid pellets

The aim of the current study was the development of a new pellet based self-emulsifying (SE) drug delivery system for the oral delivery of poorly soluble drugs. Furthermore, we wanted to investigate the influence of physiological dilution media and enzymatic digestion on the solubilization capacity of the formulation for the model drug Progesterone. Lipid mixtures composed of Solutol ® HS 15 and medium chain glycerides were optimized with respect to their self-emulsifying properties. The liquid SE lipid was mixed with microcrystalline cellulose and transformed into pellets by extrusion/spheronization. The pellets were characterized for size, shape, surface characteristics and friability. In vitro dissolution and digestion experiments were carried out using physiological dissolution media. The droplet diameter of the dispersed SE mixtures was largely affected by changing the oil to Solutol ® HS 15 ratio. Moreover, digestion of SE mixtures changed the solubilization capacity for Progesterone. Pellets with good properties (size, shape and friability) have been produced through the incorporation of a selected SE mixture into MCC. In conclusion, extrusion/spheronization is a suitable process to produce solid self-emulsifying pellets with up to 40% load of a liquid SE mixture. Digestion induces a change in lipid composition which affects the solubilization capacity of the lipid phase.

Studies on Preparation and Absolute Bioavailability of a Self-Emulsifying System Containing Puerarin

The purpose of the study was to develop an optimum formulation of self-emulsifying drug delivery systems (SEDDS) containing puerarin and to evaluate its absolute bioavailability. Using oleic acid as oil, Tween-80 as surfactant and propylene glycol as cosurfactant, a series of mixtures comprising oleic acid, propylene glycol and Tween 80 were prepared and their self-emulsifying properties were studied. Pseudo-ternary phase diagrams were constructed to identify the efficient self-emulsification region and particle sizes of the resultant emulsions were determined using a laser diffraction sizer. From these studies, an optimized formulation consisting of oil (17.5%), Tween-80 (34.5%) and cosurfactant (34.5%) was selected and its absolute bioavailability in beagle dogs after oral administration was about 24.8%. The data suggest the use of SEDDS to provide a potential way of puerarin administered orally.