Solid Self-emulsifying Drug Delivery System Research Articles

Solid Self-Nanoemulsifying Drug Delivery Systems of Furosemide: In Vivo Proof of Concept for Enhanced Predictable Therapeutic Response.

Liquid self-nano emulsifying drug delivery systems (SNEDDS) of furosemide (FSM) have been explored as a potential solution for enhancing solubility and permeability but are associated with rapid emulsification, spontaneous drug release, and poor in vivo correlation. To overcome the shortcoming, this study aimed to develop liquid and solid self-emulsifying drug delivery systems for FSM, compare formulation dynamics, continue in vivo therapeutic efficacy, and investigate the advantages of solidification. For this purpose, liquid SNEDDS (L-SEDDS-FSM) were formed using oleic acid as an oil, chremophore EL, Tween 80, Tween 20 as a surfactant, and PEG 400 as a co-surfactant containing 53 mg/mL FSM. At the same time, solid SNEDDS (S-SEDDS-FSM) was developed by adsorbing liquid SNEDDS onto microcrystalline cellulose in a 1:1 ratio. Both formulations were evaluated for size, zeta potential, lipase degradation, and drug release. Moreover, in vivo diuretic studies regarding urine volume were carried out in mice to investigate the therapeutic responses of liquid and solid SNEDDS formulations. After dilution, L-SEDDS-FSM showed a mean droplet size of 115 ± 4.5 nm, while S-SEDDS-FSM depicted 116 ± 2.6 nm and zeta potentials of -5.4 ± 0.55 and -6.22 ± 1.2, respectively. S-SEDDS-FSM showed 1.8-fold reduced degradation by lipase enzymes in comparison to L-SEDDS-FSM. S-SEDDS-FSM demonstrated a sustained drug release pattern, releasing 63% of the drug over 180 min, in contrast to L-SEDDS-FSM, exhibiting 90% spontaneous drug release within 30 min. L-SEDDS-FSM exhibited a rapid upsurge in urine output (1550 ± 56 μL) compared to S-SEDDS-FSM, showing gradual urine output (969 ± 29 μL) till the 4th h of the study, providing sustained urine output yet a predictable therapeutic response. The solidification of SNEDDS effectively addresses challenges associated with spontaneous drug release and precipitation observed in liquid SNEDDS, highlighting the potential benefits of solid SNEDDS in improving the therapeutic response of furosemide.

Novel solid self-emulsifying drug delivery system to enhance oral bioavailability of cabazitaxel

In this study, a novel cabazitaxel solid self-emulsifying drug delivery system (CTX S-SEDDS) was developed by solvent evaporation and liquid–solid compression technology, which overcame the limitations of the traditional SEDDS and improved the oral bioavailability. From the results of solubility, pseudo-ternary phase diagram, and single-factor analysis, Tween 80 (surfactant), Tricaprylin (oil), and Glyceryl monooleate (oil) with the ratio of 30:55:15 showed optimized particle size (140.87 nm), short emulsification and high cabazitaxel (CTX) loading capacity (50 mg·g−1). Based on the liquid–solid compression mathematical model, Syloid XDP3050 was determined as carrier material and Syloid 244FP as coating material. The prepared CTX S-SEDDS showed excellent flowability, tabletability, and reconstitution property. In vivo pharmacokinetics in rats demonstrated the absolute bioavailability of CTX S-SEDDS (17.27 %) was significantly enhanced compared with CTX solution (1.69 %), which was close to that of CTX-SEDSS (20.48 %). Lymphatic absorption was verified by in vitro imaging to be an important absorption route for self-emulsifying preparations. These results suggested that CTX S-SEDDS could enhance oral bioavailability of poorly water-soluble drug cabazitaxel while avoiding SEDDS limitations and harnessing the dual advantages of solid and liquid preparations.

Development of superior chitosan–EDTA microparticles as an adsorbent base for solidifying the self-emulsifying drug delivery systems

BackgroundThe present study focused on developing a superior adsorbent carrier (microparticles) to solidify the self-emulsifying drug delivery system. The two approaches, solvent evaporation and spray drying, were explored to synthesize the microparticles using chitosan (CH) and EDTA disodium. The 32 full factorial design was applied to optimize the microparticle process produced by both methods.ResultsThe various characterization evaluations of the microparticles revealed amide linkages between the CH and EDTA disodium, and XRD results showed that microparticles were amorphous. The SE-CHEM (C2) and SD-CHEM (Y1) optimized microparticles were free-flowing and had percentage yield (%), 96 ± 1.2 and 58 ± 1.1, zeta potential (mV), 9 ± 0.44 and 4 ± 0.13, and particle size (μm), 3 ± 0.57 and 2 ± 0.4, respectively. SEM images showed uneven surfaces with wide void spaces and flaky texture for optimized microparticles Y1 and C2, respectively. The SE-CHEM (C2) had an oil adsorption capacity (OAC %) of 46 ± 0.54 and 60 ± 0.77, and oil desorption capacity (ODC %), 38 ± 0.65 and 56 ± 0.86, for Labrafac and Cremophor RH 40, respectively. The SD-CHEM (Y1) had an oil adsorption capacity (OAC %) of 59 ± 0.71 and 68 ± 0.39, and oil desorption capacity (ODC %), 54 ± 0.11 and 65 ± 0.74, for Labrafac and Cremophor RH 40, respectively. In the surface free energy components analysis, the SE-CHEM (C2) had an enhanced dispersive component [γLW (mJ/m2)] of 32 ± 0.68 and 37 ± 0.47 for Labrafac and Cremophor RH 40, respectively. The SD-CHEM (Y1) had an enhanced dispersive component [γLW (mJ/m2)] of 48 ± 0.7 and 52 ± 0.41 for Labrafac and Cremophor RH 40, respectively. The SE-CHEM (C2) had enhanced dynamic advancing contact angles [θa (°)] of 75 ± 0.19 and 78 ± 0.75 for Labrafac and Cremophor RH 40, respectively. The SD-CHEM (Y1) had enhanced dynamic advancing contact angles [θa (°)] of 74 ± 0.6 and 80 ± 0.21 for Labrafac and Cremophor RH 40, respectively.ConclusionAll the findings indicate that the microparticles have superior characteristics to serve as the adsorbent base for solid self-emulsifying drug delivery systems.

Formulation and statistical optimization of clozapine solid self emulsification system for improving the dissolution properties

Clozapine is an atypical antipsychotic drug that exhibits low bioavailability (>27%) due to poor solubility and higher hepatic metabolism. The present investigation was aimed to prepare a solid self-emulsifying drug delivery system (S-SEDDS) of clozapine to improve its dissolution properties. Various long-chained natural dietary oils, surfactants, and cosurfactants were screened to evaluate their drug solubilization ability and emulsification efficiency which was measured in terms of % transmittance of the formed system. A ternary phase diagram was generated to identify compositions that were able to form emulsions with the required globule size. The simplex lattice design was used to understand the effect of change in the composition of excipients on important product characteristics. The regression analysis suggested a significant effect of the change in the proportion of composition on selected response variables. The Liquid-SEDDS (L-SEDDS) were mixed with solid carriers (aerosil-200 and MCC) to form S-SEDDS. The results of Differential Scanning Calorimetry (DSC) and Powder X-Ray Diffraction (PXRD) studies indicated the complete transformation of the crystalline drug into the amorphous or molecular level dispersed state for the S-SEDDS prepared using aerosil-200 as a carrier. The results of in-vitro dissolution studies proved significant improvement in the dissolution of the drug from the S-SEDDS compared to the pure drug.

Development, Characterization and In-vitro Evaluation of Solid Self-Emulsifying Drug Delivery Systems (S-SEDDS) Containing Valsartan

Hipertansiyon, kardiyovasküler hastalık için ana risk faktörüdür. Valsartan, anjiyotensin II'nin anjiyotensin Tip 1 reseptörü üzerindeki etkisini spesifik olarak bloke ederek yaygın olarak kullanılan, etkili ve iyi tolere edilen antihipertansif ajandır. Ancak gastrointestinal sistemin üst kısmından emilir ve buranın asidik ortamı nedeniyle bu bölgede az çözünür ve oral biyoyararlanımı sadece %25'tir. Bu çalışmanın amacı, Valsartan'ın (VST) ticari formülasyonuna alternatif olarak yeni bir dozaj formu geliştirmektir. Bu amaçla, VST’ın çözünürlüğünü artırmak ve pH'tan bağımsız bir çözünürlüğe sahip olan katı kendiliğinden emülsifiye olabilen ilaç taşıyıcı sistem (S-SEDDS) formülasyonu geliştirmek hedeflenmiştir. VST'ın en yüksek çözünürlük gösterdiği SEDDS bileşenlerini belirlemek için çözünürlük çalışmaları yapılmıştır. Çözünürlük çalışmalarına göre; yağ fazı olarak izopropil miristat (3.5 mg/mL), yüzey etkin maddeler olarak Capyrol 90 (19.8 mg/mL) ve Tween 20 (32.5 mg/mL), yardımcı yüzey etkin madde olarak ise Transcutol HP (168.9 mg/mL) kullanılmıştır. Çözünürlük çalışmaları ile belirlenen yardımcı maddeler ile üçgen faz diyagramları çizilmiştir. VST içeren SEDDS formülasyonları Avicel pH101 ve Hidroksipropil metil selüloz’a (HPMC) ayrı ayrı yaş granülasyon tekniği ile adsorbe edilmiş ve karakterizasyon çalışmaları yapılmıştır. Geliştirilen VST-SEDDS, VST-SEDDS-Avicel ve VST-SEDDS-HPMC formülasyonları pH 1.2 ortamında ticari ürüne göre VST salınımı arttırmıştır. Ayrıca VST-SEDDS-Avicel formülasyonunun açlık, tokluk durumlarından ve pH değişiminden etkilenmediği gözlenmiştir. Bu nedenle VST-SEDDS-Avicel formülasyonunun, pH'tan bağımsız çözünürlüğü arttırdığı ve antihipertansif tedavi için potansiyel bir formülasyon adayı olabileceği söylenebilmektedir.

Twin Screw Melt Granulation: A Single Step Approach for Developing Self-Emulsifying Drug Delivery System for Lipophilic Drugs.

The current research aims to improve the solubility of the poorly soluble drug, i.e., ibuprofen, by developing self-emulsifying drug delivery systems (SEDDS) utilizing a twin screw melt granulation (TSMG) approach. Gelucire® 44/14, Gelucire® 48/16, and Transcutol® HP were screened as suitable excipients for developing the SEDDS formulations. Initially, liquid SEDDS (L-SEDDS) were developed with oil concentrations between 20-50% w/w and surfactant to co-surfactant ratios of 2:1, 4:1, 6:1. The stable formulations of L-SEDDS were transformed into solid SEDDS (S-SEDDS) using a suitable adsorbent carrier and compressed into tablets (T-SEDDS). The S-SEDDS has improved flow, drug release profiles, and permeability compared to pure drugs. The existence of the drug in an amorphous state was confirmed by differential scanning calorimetry (DSC) and powder X-ray diffraction analysis (PXRD). The formulations with 20% w/w and 30% w/w of oil concentration and a 4:1 ratio of surfactant to co-surfactant have resulted in a stable homogeneous emulsion with a globule size of 14.67 ± 0.23 nm and 18.54 ± 0.55 nm. The compressed tablets were found stable after six months of storage at accelerated and long-term conditions. This shows the suitability of the TSMG approach as a single-step continuous manufacturing process for developing S-SEDDS formulations.

Fabrication and Evaluation of Colloidal Silica Containing Powders for Solid Self-emulsifying Drug Delivery System of Poorly Water Soluble Rivaroxaban

Fabrication and Evaluation of Colloidal Silica Containing Powders for Solid Self-emulsifying Drug Delivery System of Poorly Water Soluble Rivaroxaban

Formulation and processing of solid self-emulsifying drug delivery systems (HME S-SEDDS): A single-step manufacturing process via hot-melt extrusion technology through response surface methodology

The objective of the current study is the formulation development and manufacturing of solid self-emulsifying drug delivery systems (HME S-SEDDS) via a single-step continuous hot-melt extrusion (HME) process. For this study, poorly soluble fenofibrate was selected as a model drug. From the results of pre-formulation studies, Compritol® HD5 ATO, Gelucire® 48/16, and Capmul® GMO-50 were selected as oil, surfactant and co-surfactant respectively for manufacturing of HME S-SEDDS. Neusilin® US2 was selected as a solid carrier. The design of experiments (response surface methodology) was employed to prepare formulations via a continuous HME process. The formulations were evaluated for emulsifying properties, crystallinity, stability, flow properties and drug release characteristics. The prepared HME S-SEDDS showed excellent flow properties, and the resultant emulsions were stable. The globule size of the optimized formulation was 269.6 nm. The DSC and XRD studies revealed the amorphous nature of the formulation and FTIR studies showed no significant interaction between fenofibrate and excipients. The drug release studies showed significant (p < 0.05) improvement in solubility compared to the pure drug (DE15 = 45.04 for the optimized formulation), as >90% of drug release was observed within 15 min. The stability studies for the optimized formulation were conducted for 3 months at 40 °C/75% RH.

Concurrent oral delivery of non-oncology drugs through solid self-emulsifying system for repurposing in hepatocellular carcinoma

Objective Present study aimed to identify a safe and effective non-oncology drug cocktail as an alternative to toxic chemotherapeutics for hepatocellular carcinoma treatment. The assessment of cytotoxicity of cocktail (as co-adjuvant) in combination with chemotherapeutic docetaxel (DTX) is also aimed. Further, we aimed to develop an oral solid self-emulsifying drug delivery system (S-SEDDS) for the simultaneous delivery of identified drugs. Significance The identified non-oncology drug cocktail could overcome the shortage of anticancer therapeutics and help to reduce cancer-related mortality. Moreover, the developed S-SEDDS could be an ideal system for concurrent oral delivery of non-oncology drug combinations. Methods The non-oncology drugs (alone and in combinations) were screened in vitro for anticancer effect (against HepG2 cells) using (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide; MTT) dye assay, and cell cycle arresting and apoptotic behaviors using the fluorescence-activated cell sorting (FACS) technique. The S-SEDDS is composed of drugs such as Ketoconazole (KCZ), Disulfiram (DSR), Tadalafil (TLF), and excipients like span-80, tween-80, soybean oil, Leciva S-95, Poloxamer F108 (PF-108), and Neusilin® US2 (adsorbent carrier) was developed and characterized. Results The cocktail composed of KCZ, DSR, and TLF has showed substantial cytotoxicity (at the lowest concentration of 3.3 picomoles), HepG2 cell arrest at G0/G1 and S phases, and substantial cell death via apoptosis. The Docetaxel (DTX) inclusion into this cocktail has further resulted in increased cytotoxicity, cell arrest at the G2/M phase, and cell necrosis. The optimized blank liquid SEDDS that remains transparent without phase separation for more than 6 months is used for the preparation of drug-loaded liquid SEDDS (DL-SEDDS). The optimized DL-SEDDS with low viscosity, good dispersibility, considerable drug retention upon dilution, and smaller particle size is further converted into drug-loaded solid SEDDS (DS-SEDDS). The final DS-SEDDS demonstrated acceptable flowability and compression characteristics, significant drug retention (more than 93%), particle size in nano range (less than 500 nm) and nearly spherical morphology following dilutions. The DS-SEDDS showed substantially increased cytotoxicity and Caco-2 cell permeability than plain drugs. Furthermore, DS-SEDDS containing only non-oncology drugs caused lower in vivo toxicity (only 6% body weight loss) than DS-SEDDS containing non-oncology drugs with DTX (about 10% weight loss). Conclusion The current study revealed a non-oncology drug combination effective against hepatocellular carcinoma. Further, it is concluded that the developed S-SEDDS containing non-oncology drug combination alone and in combination with DTX could be a promising alternative to toxic chemotherapeutics for the effective oral treatment of hepatic cancer.

Improvement of dissolution profile of eplerenone with solidified self-emulsifying drug delivery systems (S-SEDDS)

Context Eplerenone is a member of antihypertensives used individually or in combination with other medicines. Eplerenone exhibits poor solubility and is considered a class II drug. Objective Increasing the solubility of eplerenone by using both liquid and solid self-emulsifying drug delivery systems as an alternative to its marketed tablet product. Methods Solubility studies of eplerenone were done with different oils, surfactants, and co-surfactants to determine which one has the highest solubility for eplerenone and determine the preference in the formulations of liquid self-emulsifying drug delivery system. The solidification process was carried out with the adsorption to solid carrier method. Optimal ratios of components were specified with the pseudo-ternary phase diagram technique. Self-emulsifying drug delivery system formulations were characterized in terms of chemical interaction, droplet size/distribution, crystallization behaviors, and rheological evaluation. In vitro drug release studies were conducted and compared to pure drugs and marketed products. Results The solubility screening results showed high solubility of EPL in triacetin (11.99 mg/mL) as oil, Kolliphor®EL (≈ 2.65 mg/mL), and Tween80 (≈ 1.91 mg/mL) as surfactant and polyethylene glycol 200 (PEG200) (≈ 8.50 mg/mL), dimethyl sulfoxide (≈ 7.57 mg/mL), TranscutolP (≈ 6.03 mg/mL) as co-surfactant, respectively. Rheology studies revealed that liquid self-emulsifying drug delivery formulations exhibited non-Newtonian pseudoplastic flow. Conclusion Solid self-emulsifying drug delivery systems prepared with Aerosil and Neusilin have shown tremendous improvement in terms of eplerenone dissolution by releasing the entire dose with boosted effect within 5 and 30 min respectively compared to the marketed product and pure eplerenone (p < 0.05).

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.

Formulation and Evaluation of Castor Oil Containing Self-emulsifying Pellets by Using Design of Experiment

Abstract: Background/Objectives: The objective of the study was to examine the feasibility of extrusion/ spheronization techniques for formulation of castor oil loaded self-emulsifying pellets. The study was also aimed at optimization of the self-emulsifying pellet system with design of experiments. Materials and Methods: Various surfactants and co-surfactants were tested for their ability to emulsify castor oil. The proportion of components (castor oil, surfactant and co-surfactant) in self-emulsifying pellets was optimized using a D-optimal mixture design. During optimization, the effect of composition of oil(X1), surfactant(X2) and cosurfactant(X3) blend on responses like dispersion time (Y1), resultant globule size (Y2) and polydispersity index (Y3) was studied. The developed self-emulsifying mixture was further loaded on pellet formulation using extrusion spheronization technique. Results: The application of D-optimal mixture design resulted in 16 batches, out of which the optimized batch consists of castor oil (30.92%), Cremophore EL (58.56%) and PEG 400(10.51%) having dispersion time of 53 sec, globule size of 242 nm and polydispersity index of 0.243 with desirability value of 1. All the formulation components affected the performance of pellets significantly. Free flowing pellets were obtained with 30% of oil loading. Conclusion: The self-emulsifying pellets of castor oil were successfully optimized with mixture design. The developed system containing castor oil can be used for orally for conditions like arthritis or can also serve as a carrier system for any drug or herbal active. Keywords: Solid self-emulsifying drug delivery system, Castor oil, Self-emulsifying pellets, Extrusion spheronization, Dispersion time.

Liquid and Solid Self-Emulsifying Drug Delivery Systems to Improve Dissolution of Carvedilol

Liquid and Solid Self-Emulsifying Drug Delivery Systems to Improve Dissolution of Carvedilol

Development of a Solid Self-emulsifying Drug Delivery System of Boswellia serrata

Development of a Solid Self-emulsifying Drug Delivery System of Boswellia serrata

Fabrication and Evaluation of Solid Self Emulsifying Drug Delivery System of Dolutegravir sodium by using Adsorption to Solid Carrier Techniques

The objective of this work was to design and characterize liquid and solid self-emulsifying drug delivery systems (SEDDS) for poorly soluble Dolutegravir Sodium. To optimize the composition of liquid Dolutegravir Sodium-SEDDS, solubility tests, pseudoternary phase diagrams, emulsification studies and other in vitro examinations (thermodynamic stability, droplet size and zeta potential analysis) were performed. The central composite design was employed to optimize the formulation variables, Capmul MCM (oil), Tween 80 (surfactant) and Propylene glycol (co-surfactant). Liquid self-emulsifying drug delivery system was appraised for determination of self emulsifying time, globule size and drug release. TEM study confirmed the uniform oil globules of the optimized liquid formulation. The optimized liquid formulation was formulated into free-flowing powder (S-SEDDS) by adsorption on the materials like Aerosil 200, Neusilin US2 and compressed into tablets. The solid state characterization of S-SEDDS powder was performed by using DSC, PXRD and SEM to investigate the physical nature of the drug. Further, the accelerated stability studies for 6 months revealed that S-SEDDS of Dolutegravir Sodium was found to be stable without any significant change in physico-chemical properties. S-SEDDS of Dolutegravir Sodium with improved dissolution profile was successfully prepared by using Neusilin US2 as an adsorbent carrier as compared to marketed sample.

Lipid-based solubilization technology via hot melt extrusion: promises and challenges

Introduction Self-emulsifying drug delivery systems (SEDDS) are a promising strategy to improve the oral bioavailability of poorly water-soluble drugs (PWSD). The excipients of SEDDS enable permeation through the mucus and gastro-intestinal barrier, inhibiting efflux transporters (e.g. P-glycoprotein) of drugs. Poor drug loading capacity and formulation instability are the main setbacks of traditional SEDDS. The use of polymeric precipitation inhibitors was shown to create supersaturable SEDDS with increased drug payload, and their solidification can help to overcome the instability challenge. As an alternative to several existing SEDDS solidification technologies, hot melt extrusion (HME) holds the potential for lean and continuous manufacturing of supersaturable solid-SEDDS. Despite being ubiquitously applied in solid lipid and polymeric processing, HME has not yet been widely considered for the preparation of SEDDS. Areas covered The review begins with the rationale why SEDDS as the preferred lipid-based delivery systems (LBDS) is suitable for the oral delivery of PWSD and discusses the common barriers to oral administration. The potential of LBDS to surmount them is discussed. SEDDS as the flagship of LBDS for PWSD is proposed with a special emphasis on solid-SEDDS. Finally, the opportunities and challenges of HME from the lipid-based excipient (LBE) processing and product performance standpoint are highlighted. Expert opinion HME can be a continuous, solvent-free, cost-effective, and scalable technology for manufacturing solid supersaturable SEDDS. Several critical formulations and process parameters in successfully preparing SEDDS via HME are identified.

Formulation of oily tocotrienols as a solid self-emulsifying dosage form for improved oral bioavailability in human subjects

Self-emulsifying drug delivery systems (SEDDS) have been shown to enhance the water-solubility and oral bioavailability of poorly water-soluble compound. Solid SEDDS (s-SEDDS) address the stability and compatibility issues associated with conventional liquid SEDDS, but have limitations including the use high amounts of surfactants and complex processes resulting in low final drug loading and poor powder flow. The aim of the present study was to formulate a solid dosage form containing 100 mg tocotrienols using the optimized s-SEDDS powder we developed with tocotrienol-rich fraction (TRF) as the model liquid active substance via a simple adsorption method. The s-SEDDS granules formulated via wet-granulation with PVP K30 showed excellent flow properties, retained good emulsification efficiency, with submicron emulsion droplet size and dissolution profile of 75–100%. The oral bioavailability evaluated in human subjects showed that of the s-SEDDS capsules was comparable absorption to that of the commercial liquid self-emulsifying product Tocovid Suprabio™, which demonstrated enhanced tocotrienols’ bioavailability by 3-fold compared to that of an oily non self-emulsifying preparation. In conclusion, the bioavailability of tocotrienols from the s-SEDDS was encouraging and can be a promising alternative and a convenient solid dosage form that can significantly enhance the oral bioavailability of the tocotrienols.

Formulation and In Vivo Evaluation of a Solid Self-Emulsifying Drug Delivery System Using Oily Liquid Tocotrienols as Model Active Substance.

Self-emulsifying drug delivery systems (SEDDS) can improve the oral bioavailability of poorly water-soluble drugs. Solid self-emulsifying drug delivery systems (s-SEDDS) offer several advantages including improved drug stability, ease of administration, and production. Most compounds employed in developing s-SEDDS are solid in nature, with a high amount of surfactants added. The aim of this study was to develop an s-SEDDS using a tocotrienol-rich fraction (TRF) as the model liquid active substance via a simple adsorption method. The solid formulation was developed using magnesium aluminosilicate as the carrier with 70% TRF and 30% surfactants (poloxamer and Labrasol®). The formulation showed good self-emulsification efficiency with stable emulsion formed, excellent powder flowability, and small emulsion droplet size of 210–277 nm. The s-SEDDS with combined surfactants (poloxamer and Labrasol®) showed a faster absorption rate compared to preparations with only a single surfactant and enhanced oral bioavailability (3.4–3.8 times higher) compared to the non-self-emulsifying oily preparation when administered at a fasted state in rats. In conclusion, an s-SEDDS containing a high amount of TRF was successfully developed. It may serve as a useful alternative to a liquid product with enhanced oral bioavailability and the added advantage of being a solid dosage form.

Effects of Formulation and Manufacturing Process on Drug Release from Solid Self-emulsifying Drug Delivery Systems Prepared by High Shear Mixing.

This study sought to investigate the influence of formulation and process factors of the high shear mixing (HSM) on the properties of solid self-emulsifying drug delivery systems (S-SEDDS) containing the model drug carvedilol (CAR). Firstly, liquid SEDDS (L-SEDDS) were prepared by mixing castor oil with different proportions of surfactant (Solutol or Kolliphor RH40) and cosolvent (Transcutol or PEG400). A miscible L-SEDDS with high drug solubility (124.3mg/g) was selected and gave rise to 10% (m/m) CAR loaded-emulsion with reduced particle size. Then, a factorial experimental design involving five component's concentration and two process factors was used to study the solidification of the selected L-SEDDS by HSM. CAR content, diffractometric profile, and in vitro dissolution were determined. Morphological and flow analyses were also performed. Porous and spherical particles with mean sizes ranging from 160 to 210µm were obtained. Particle size was not affected by any formulation factor studied. Powder flowability, in turn, was influenced by L-SEDDS and crospovidone concentration. CAR in vitro dissolution from S-SEDDS was significantly increased compared to the drug as supplied and was equal (pH 1.2) or lower (pH 6.8) than that determined for L-SEDDS. Colloidal silicon dioxide decreased drug dissolution, whereas an increase in water-soluble diluent lactose and L-SEDDS concentration increased CAR dissolution. The proper selection of liquid and solid constituents proved to be crucial to developing an S-SEDDS by HSM. Indeed, the results obtained here using experimental design contribute to the production of S-SEDDS using an industrially viable process.

Characterization and Optimization of Oral Solid Supersaturable Self-emulsifying Drug Delivery System of Cilostazol

Objective: This study aimed to prepare tablets containing solid supersaturable self-emulsifying drug delivery system (S-SEDD) of cilostazol for oral use. Method: To improve drug dissolution and so bioavailability for cilostazol (calss II drug) as well as reducing the amount of additives (except for drug =50 mg), liquid S-SEDD of cilostazol were prepared. In this study the liquid supersaturable formula was converted into a solid supersaturable self-emulsifying form using different amounts of two different types of the adsorbents (avicel 101 and aerosil 200). Accordingly; six-formulas (SS1-SS6) were prepared and evaluated applying pre-compression evaluation and the best formula was SS3 formula having an amorphous homogenous free-flowing property and used to prepare tablets using direct compression method. Consequently; six tablet formulas (T1-T6) containing different types and amounts of additives were prepared and evaluated applying post-compression parameters and in-vitro drug release. Result: The best tablet formula was T2 formula which showed high dissolution profile under sink and non-sink condition in comparison to conventional marketed tablet indicating that it kept its supersaturable self-emulsification in-vitro with faster drug release which may lead to improve drug absorption and bioavailability with a fast onset of action. Conclusion: This work succeeded in converting the prepared cilostazol liquid S-SEDD to solid SEDD which is compressed into an immediate release tablets that disintegrate and spontaneously emulsified to form supersaturable system in the GIT which improved drug solubility, release and consequently may enhance its absorption and bioavailability leading to reducing dose size and drug/excipient size effects.