SMEDDS Formulation Research Articles

Lipid-based systems with precipitation inhibitors as formulation approach to improve the drug bioavailability and/or lower its dose: a review.

Lipid-based systems, such as self-microemulsifying systems (SMEDDS) are attracting strong attention as a formulation approach to improve the bioavailability of poorly water-soluble drugs. By applying the "spring and parachute" strategy in designing supersaturable SMEDDS, it is possible to maintain the drug in the supersaturated state long enough to allow absorption of the complete dose, thus improving the drug's bio-availability. As such an approach allows the incorporation of larger amounts of the drug in equal or even lower volumes of SMEDDS, it also enables the production of smaller final dosage forms as well as decreased gastrointestinal irritation, being of particular importance when formulating dosage forms for children or the elderly. In this review, the technological approaches used to prolong the drug supersaturation are discussed regarding the type and concentration of polymers used in liquid and solid SMEDDS formulation. The addition of hypromellose derivatives, vinyl polymers, polyethylene glycol, polyoxyethylene, or polymetacrylate copolymers proved to be effective in inhibiting drug precipitation. Regarding the available literature, hypromellose has been the most commonly used polymeric precipitation inhibitor, added in a concentration of 5 % (m/m). However, the inhibiting ability is mainly governed not only by the physicochemical properties of the polymer but also by the API, therefore the choice of optimal precipitation inhibitor is recommended to be evaluated on an individual basis.

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.

Design, Optimization and Characterization of Self-Nanoemulsifying Drug Delivery Systems of Bilastine

Self-nanoemulsifying drug delivery systems are innovative methods that have the potential to resolve a variety of drug formulation issues, including solubility, stability and bioavailability. Bilastine is a potent and highly selective H1-antihistamine. The aim of this study is to develop bilastine as an oral self-nanoemulsion to enhance its permeability from prepared formulas and possibility of lymphatic transport. Based on the solubility investigations of bilastine in some oils, surfactants and cosurfactants, fifteen formulae of liquid SNEDDS were created utilizing oleic acid, tween 60 and transcutol as oil, surfactant and co-surfactant respectively. Pseudoternary phase diagrams were used to evaluate the component phase behavior and the area of the nanoemulsion. The prepared formulas were evaluated for particle size, polydispersity index, zetapotential, self-emulsification time, drug content, and robustness to dilution. When compared to the pure drug powder, the produced SMEDDS formulations showed enhanced drug release. This study's findings showed that a formula 8 with a 20% oleic acid, 40% tween 60, and 40% transcutol composition exhibited lower particle size and higher zetapotential with acceptable drug content compared to other formulas and better in-vitro drug release characteristics than pure bilastine powder. All of these criteria favor the development of self-nano emulsifying drug delivery systems as a potential approach to enhance the bioavailability of drugs like bilastine that are poorly soluble. Keywords: Bilastine, SNEDDS

Comparative Evaluation of Antidiabetic Activity of Ethanolic Leaf Extract of Clematis Gouriana and Their SMEDDS Formulation in Streptozotocin Induced Diabetic Rats

Comparative Evaluation of Antidiabetic Activity of Ethanolic Leaf Extract of Clematis Gouriana and Their SMEDDS Formulation in Streptozotocin Induced Diabetic Rats

Comparative Evaluation of Antidiabetic Activity of Ethanolic Leaf Extract of Clematis Gouriana and Their SMEDDS Formulation in Streptozotocin Induced Diabetic Rats

Comparative Evaluation of Antidiabetic Activity of Ethanolic Leaf Extract of Clematis Gouriana and Their SMEDDS Formulation in Streptozotocin Induced Diabetic Rats

Abstract 706: Efficacy evaluation of BR-9001, a SMEDDS formulation of 3,3’-diindolylmethane, as an inhibitor of preneoplastic and neoplastic lesion development in the prostate of Hi-Myc mice

Abstract Self-Microemulsifying Drug Delivery Systems (SMEDDS) can greatly increase the bioavailability of agents with limited solubility. Studies were performed to characterize the efficacy of BR-9001, a SMEDDS formulation of 3,3’-diindolylmethane (DIM), in preventing preneoplastic and neoplastic prostate lesion development in Hi-Myc mice. Beginning at age 8 weeks, groups of 105 male Hi-Myc mice received twice daily oral (gavage) administration of BR-9001 (BioResponse LLC, Boulder, CO) at DIM-equivalent doses of 0 (vehicle control), 200, or 400 mg/kg/dose. At ages 4 months, 5.5 months, and 7 months, cohorts of 35 mice/group were euthanized and necropsied; at each time point, tissues were collected from 25 mice/group for pathology; 5 mice/group for analysis of DIM levels in the plasma and prostate; and 5 mice/group for biomarker analysis. Prostate lesion development in pathology cohorts was determined by microscopic evaluation of step sections through the entire accessory sex gland block. Plasma and prostate levels of DIM were quantitated by LC-MS/MS; biomarkers were analyzed by RT-PCR. Administration of BR-9001 produced dose-related levels of DIM in the plasma and prostate at all time points. However, BR-9001 provided at most limited protection against prostate lesion development. Most lesions were identified in the lateral prostate (LP), where statistically significant reductions in incidences of murine prostatic intraepithelial neoplasias (mPIN) were seen in 4-month-old mice receiving the high dose of BR-9001 and in 5.5-month-old and 7-month-old mice receiving the low dose of BR-9001. Reductions in mPIN incidence in groups receiving BR-9001 were due to lower incidences of small mPIN lesions; incidences of large mPIN were significantly increased at 5.5 months in both groups receiving BR-9001. BR-9001 had no statistically significant effect on % occupancy of the LP by mPIN, the incidence of microinvasive mPIN in the LP, or cancer incidence in the LP. In the anterior prostate (AP), incidences of atypical hyperplasia were similar in all groups. However, at all necropsy time points, mice receiving the high dose of BR-9001 demonstrated significant increases in the incidences of moderate to marked AP atypia; these increases were accompanied by decreases in the incidence of mice with slight to moderate AP atypia. None of 22 potential molecular biomarkers were found to be clearly linked to development and progression of prostate lesions in Hi-Myc mice. Despite the presence of measurable concentrations of DIM in the plasma and prostate in mice in both treated groups at all time points, BR-9001 demonstrated equivocal efficacy in preventing the development of preneoplastic and neoplastic lesions in the Hi-Myc mouse model of prostate cancer. [Supported by NCI HHSN261201500042I/HHSN26100003.] Citation Format: Genoveva Murillo, Gina Qualter, Xinjian Peng, Miguel Muzzio, Elizabeth R. Glaze, Altaf Mohammed, Maarten C. Bosland, David L. McCormick. Efficacy evaluation of BR-9001, a SMEDDS formulation of 3,3’-diindolylmethane, as an inhibitor of preneoplastic and neoplastic lesion development in the prostate of Hi-Myc mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 706.

Natural bio functional lipids containing solid self-microemulsifying drug delivery system of Canagliflozin for synergistic prevention of type 2 diabetes mellitus

Type 2 Diabetes Mellitus (T2DM) is one of the prevalent metabolic disorders and is the leading cause of death across the globe. In the present invention, we reported significant synergistic anti-diabetic efficacy of novel SGLT II inhibitor, Canagliflozin (CFZ) with natural phytoconstituent, Trigonelline (TGL) in fenugreek oil using a self-microemulsifying based formulation. The optimized liquid SMEDD formulation (NADF) containing fenugreek oil (18.11% w/w), vitamin E TPGS (53.40% w/w) and linalool (10.12% w/w) were optimized by Design of Experiments and produces nanoparticulate stable microemulsion in vitro. Conversion to solid SMEDDS (NADF-SD) was facilitated by adsorption onto natural biosorbent coffee husk. The optimized solid formulation containing CFZ was in amorphous state with enhanced surface area, negligible chemical incompatibility and uniform drug content. Scanning electron microscopy validated the powdered SMEDDS′ spherical form. The release behavior of CFZ in NADF-SD in diverse biorelevant environments is enhanced by in vitro dissolution. Furthermore, neither pure CFZ nor the marketed product had any food impact. The permeability of the jejunum intestinal segment in rats was remarkable, as validated by confocal microscopy. In comparison to a pure drug and a commercial product, these trials show a 3.99 and 2.56 fold increase in Cmax and a 2.23 and 1.56 fold increase in AUC0-24h, respectively. Through biochemical levels, urine glucose excretion investigations, and SGLT II expression in rats, pharmacodynamic examination of improved NADF-SD demonstrates enhanced anti-diabetic effectiveness of CFZ. In a nutshell, this natural lipid-based micro particulate system is well-suited for this drug's anti-diabetic activity and synergy with CFZ.

Evaluation on a supersaturatable self-microemulsifying (s-smdds) formulation of biphenyl dimethyl dicarboxylate (BDD) in Vitro and in Vivo

To enhance the dissolution and oral bioavailability of poorly water-soluble biphenyl dimethyl dicarboxylate (BDD), the supersaturatable self-microemulsifying drug delivery system (S-SMEDDS) was developed by adding a water-soluble polymer PVP to prevent precipitation of the drug and maintain a supersaturate state in vivo. Ternary phase diagrams were drawn to evaluate the microemulsification domain. The formulations were characterized by testing the physical stability of the drug, particle size and zeta potential. The pharmacokinetic study in beagle dogs was performed for the S-SMEDDS, SMEDDS formulation and the market drop pills. The optimized S-SMEDDS formulation consist of 35% (w/w) Cremphor EL35, 33% (w/w) Transcutol HP, 30% (w/w) MCT and 2% (w/w) PVPK30 of each excipient showed minimum mean droplet size (37.71 ± 0.87nm) and optimal drug release profile and better physical stability in water compared with the PVP absent SMEDDS. The in vivo studies showed that S-SMEDDS had significantly increased the Cmax and area under the plasma concentration-time curve (AUC) (P < 0.01). The S-SMEDDS formulation should be an effective oral dosage form for improving oral bioavailability of water-insoluble BDD.

A 3D-Printed Polymer-Lipid-Hybrid Tablet towards the Development of Bespoke SMEDDS Formulations.

3D printing is a rapidly growing area of interest within pharmaceutical science thanks to its versatility in creating different dose form geometries and drug doses to enable the personalisation of medicines. Research in this area has been dominated by polymer-based materials; however, for poorly water-soluble lipophilic drugs, lipid formulations present advantages in improving bioavailability. This study progresses the area of 3D-printed solid lipid formulations by providing a 3D-printed dissolvable polymer scaffold to compartmentalise solid lipid formulations within a single dosage form. This allows the versatility of different drugs in different lipid formulations, loaded into different compartments to generate wide versatility in drug release, and specific control over release geometry to tune release rates. Application to a range of drug molecules was demonstrated by incorporating the model lipophilic drugs; halofantrine, lumefantrine and clofazimine into the multicompartmental scaffolded tablets. Fenofibrate was used as the model drug in the single compartment scaffolded tablets for comparison with previous studies. The formulation-laden scaffolds were characterised using X-ray CT and dispersion of the formulation was studied using nephelometry, while release of a range of poorly water-soluble drugs into different gastrointestinal media was studied using HPLC. The studies show that dispersion and drug release are predictably dependent on the exposed surface area-to-volume ratio (SA:V) and independent of the drug. At the extremes of SA:V studied here, within 20 min of dissolution time, formulations with an SA:V of 0.8 had dispersed to between 90 and 110%, and completely released the drug, where as an SA:V of 0 yielded 0% dispersion and drug release. Therefore, this study presents opportunities to develop new dose forms with advantages in a polypharmacy context.

Preparation and evaluation of oral self-microemulsifying drug delivery system of Chlorophyll

Objective This study was aimed at improving the water solubility and oral bioavailability of Chl by self-microemulsifying drug delivery system (Chl-SMEDDS). Methods Compatibility experiments, pseudo-ternary phase diagram and central composite design were used to optimize the formulation. The selected systems were further evaluated for physical characteristics, including particle size, zeta potential, and appearance. The stability, in vitro dispersion test, and in vivo intestinal perfusion experiments were used to evaluate the SMEDDS. Results The optimal composition of Chl-SMEDDS included: Labrafil M 1944 CS (35%), kolliphor RH 40 (46%), Transcutol HP (19%) and 60 mg/g Chl. The appearance of water emulsified Chl-SMEDDS was green and transparent. The particle size, ζ-potential, and transmission electron microscopy studies showed that spherical globules of Chl-SMEDDS with a size of about 22.82 ± 1.29 nm and a negative surface charge of −24.21 ± 3.45 mV were obtained. Chl-SMEDDS could remain stable at 25 °C and 4 °C for at least 6 months. The dispersion test showed that Chl-SMEDDS dispersed spontaneously to form microemulsion after disintegration of capsule shell and 90% drug dispersed in just 30 min in pH 1.2 HCl without any drug precipitation during the test period. In vivo intestinal perfusion experiment revealed that the main absorption site for Chl-SMEDDS was duodenum. Conclusions This study indicates that SMEDDS formulation could be an effective strategy for the oral administration of Chl.

PH-Independent Dissolution and Enhanced Oral Bioavailability of Aripiprazole-Loaded Solid Self-microemulsifying Drug Delivery System.

The present study pursued the systematic development of a stable solid self-emulsifying drug delivery system (SMEDDS) of an atypical antipsychotic drug, aripiprazole (APZ), which exhibits poor aqueous solubility and undergoes extensive p-glycoprotein efflux and hepatic metabolism. Liquid SMEDDS excipients were selected on the basis of solubility studies, and the optimum ratio of surfactant/co-surfactant was determined using pseudo-ternary phase diagrams. The prepared formulations were subjected to in vitro characterization studies to facilitate the selection of optimum liquid SMEDD formulation containing 30% Labrafil® M 1944 CS, 46.7% Cremophor® EL and 23.3% PEG 400 which were further subjected to solidification using maltodextrin as a hydrophilic carrier. The optimized solid SMEDDS was extensively evaluated for stability under accelerated conditions, dissolution at various pH and pharmacokinetic profile. Solid-state attributes of the optimized solid SMEDDS indicated a marked reduction in crystallinity of APZ and uniform adsorption of liquid SMEDDS. Stability study of the solid SMEDDS demonstrated that the developed formulation retained its stability during the accelerated storage conditions. Both the optimized liquid and solid SMEDDS exhibited enhanced dissolution rate which was furthermore independent of the pH of the dissolution medium. Oral bioavailability studies in Sprague-Dawley rats confirmed quicker and greater extent of absorption with solid SMEDDS as evident from the significant reduction in Tmax in case of solid SMEDDS (0.83 ± 0.12h) as compared with commercial tablet (3.33 ± 0.94h). The results of the present investigation indicated the development of a stable solid SMEDDS formulation of APZ with enhanced dissolution and absorption attributes.

Development of an Orally Bioavailable Isoliquiritigenin Self-Nanoemulsifying Drug Delivery System to Effectively Treat Ovalbumin-Induced Asthma.

PurposeIsoliquiritigenin (ILQ), an important component of Anti-Asthma Herbal Medicine Intervention (ASHMI), had shown potent anti-asthma effect in vitro in our previous study. However, poor solubility and low bioavailability hindered in vivo application to treat asthma. This study was to develop a novel ILQ loaded self-nanoemulsifying drug delivery system (ILQ-SMEDDS) with enhanced bioavailability.MethodsThe optimized SMEDDS formulation was composed of ethyl oleate (oil phase), Tween 80 (surfactant) and PEG400 (co-surfactant) at a mass ratio of 3:6:1. The physiochemical properties of ILQ-SMEDDS, including drug content, globule size, zeta potential, scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, were characterized. And the in vitro release profile, in situ intestinal absorption, in vivo pharmacokinetic parameters and the anti-asthma effect of ILQ suspension and ILQ-SMEDDS were evaluated.ResultsThe ILQ-SMEDDS had an average globule size of 20.63 ± 1.95 nm with a polydispersity index (PDI) of 0.11 ± 0.03, and its zeta potential was −12.64 ± 2.12 mV. The cumulative release rate of ILQ from ILQ-SMEDDS to the simulated gastrointestinal tract was significantly higher than that of free ILQ suspension. And area under curve with ILQ-SMEDDS was found to be 3.95 times higher than that of ILQ suspension indicating improved bioavailability by SMEDDS. Although ILQ-SMEDDS showed a slight less effective inhibitory effect on eotaxin-1 in human lung fibroblast (HFL-1) cells than free ILQ, in an ovalbumin-induced asthma model, ILQ-SMEDDS exhibited more efficacy than ILQ suspension in improving asthma-associated inflammation, including eosinophil production, ovalbumin-specific immunoglobulin E (OVA-sIgE), interleukin 4 (IL 4), interleukin 5 (IL 5) and interferon-γ (IFN-γ). Even the low dose of ILQ-SMEDDS group (10 mg/kg) showed better anti-asthma effect than that of the ILQ suspension group (20 mg/kg).ConclusionCompared with ILQ suspension, ILQ-SMEDDS showed significantly improved bioavailability and anti-asthma effect, revealing its potential as a favorable pharmaceutical agent for treating asthma.

Polymeric Precipitation Inhibitor Assisted Supersaturable SMEDDS of Efavirenz Based on Experimental Observations and Molecular Mechanics.

Supersaturable SMEDDS, a versatile dosage form, was investigated for improving the biopharmaceutical attributes and eradicating the food effect of poorly water soluble drug efavirenz. The present research pursues the development of efavirenz loaded Supersaturable Self- Microemulsifying Drug Delivery System (SS SMEDDS) for improving biopharmaceutical performance. Preformulation studies were carried out to determine the optimized range of lipid excipients to develop stable supersaturated SMEDDS (ST SMEDDS). The SS SMEDD formulation was prepared by adding hydroxypropyl methylcellulose as a polymeric precipitation inhibitor. The developed SS SMEDDS were evaluated for supersaturation behavior by performing in vitro supersaturation studies and molecular simulations by in silico docking. Dissolution was performed in biorelevant media to simulate fed/fasted conditions in gastrointestinal regions. Absorption behavior was determined through in vivo pharmacokinetics approach. The optimized ST SMEDDS formulation containing Maisine® CC, Tween 80 and Transcutol-P exhibited thermodynamic stability with quick rate of emulsification. The optimized SS SMEDDS containing suitable polymeric precipitation inhibitor exhibited enhanced efavirenz concentration in in vitro supersaturation test. The theoretical simulations by molecular docking revealed strong intermolecular interactions with a docking score of -3.004 KJ/mol. The dissolution performance of marketed product in biorelevant dissolution media inferred the existence of food effect in the dissolution of efavirenz. However, in SS SMEDDS, no significant differences in drug release behavior under different fasted/fed conditions signify that the food effect was neutralized. In vivo pharmacokinetics revealed a significant increase in the absorption profile of efavirenz from SS SMEDDS than that of ST SMEDDS and marketed product. The designed delivery system indicated promising results in developing an effectual EFV formulation for HIV treatment.

Polymeric Precipitation Inhibitor–Based Solid Supersaturable SMEDD Formulation of Canagliflozin: Improved Bioavailability and Anti-diabetic Activity

The current investigation explores the enhanced biopharmaceutical attributes of solid supersaturable self-microemulsifying drug delivery system (Solid SS SMEDDS) for poorly water soluble drug canagliflozin (CFZ). Solid SS SMEDD formulation was prepared by spray drying using Neusilin US2 as an adsorbent. The developed SS SMEDDS were characterized for physicochemical and solid state characterizations. Theoretical molecular simulations were performed by in silico docking. BET measurements were done for evaluating surface area topography. In vitro dissolution, ex vivo permeation, and pharmacokinetics studies were performed to determine release rate, permeability, and absorption behavior, respectively. Anti-diabetic studies and histopathology were done as per standard protocols. The solid SS SMEDD formulation containing 320 mg Lauroglycol FCC, 1200 mg Tween 80, 480 mg Transcutol-P, and 2.24% w/v Poloxamer 188 as polymer-based precipitation inhibitor (PPI) was optimized. The solid state attributes of CFZ in solid SS SMEDDS revealed its molecularly dispersed state. The prepared formulation demonstrated uniform flow properties, nanoparticulate size distribution, and acceptable drug content. Theoretical simulations revealed strong intermolecular hydrogen bonding with a docking score of − 5.184 kJ/mol. In vitro dissolution studies depicted enhanced release of CFZ from solid SS SMEDDS in various dissolution media. Remarkable improvement in ex vivo permeability was observed across the jejunum segment of rat intestine. These studies revealed enhanced absorption of CFZ in rats following oral administration of solid SS SMEDDS, as compared with that of pure drug and marketed product. Pharmacological evaluation of optimized solid SS SMEDDS also revealed enhanced anti-diabetic activity, as evident from urinary glucose excretion studies and SGLT II protein expression in rat kidneys. Accelerated stability study confirmed the stability of the formulation up to 6 months storage period. The designed delivery system indicated promising results in developing an effective formulation of CFZ for diabetes mellitus.

Enhancement of Solubility and Dissolution Rate of Poorly Soluble Drug Nifedipine by Solid Sedds

Nifedipine is a dihydropyridine calci channel blocking agent belongs to biopharmaceutical classification system (BCS) class-II mainly applied in the treatment of hypertension and angina-pectoris. The objective of this work is to improve the solubility and dissolution rate of nifedipine by formulating into a solid-self micro emulsifying drug delivery system (solid smedds). Methods: Oil, Surfactant, and cosurfactant were selected by solubility screening study. For the determination of the best emulsion region, a pseudo ternary diagram was prepared. Based on solubility castor oil, tween 80 and polyethylene glycol (PEG) 400 was selected in which SCOSmix (a mixture of surfactant and cosurfactant) was 1:1. Thermodynamic stability study was performed for the determination of stable smedds formulation. These formulations were evaluated for self emulsification time, drug content analysis, robustness to dilution test, particle size analysis, and in vitro diffusion study. The optimized formulation was selected for formulating into solid-smedds by using aerosil 200 at a different ratio. SCF9L (0.65:1) was selected due to its good flow property. Then it was evaluated for particle size analysis, drug content study, differential scanning calorimetry (DSC), X-Ray Diffraction study (XRD), fourier transform infrared spectroscopy (FTIR) Scanning Electron Microscopy study (SEM) analysis, and in vitro dissolution study. Results: DSC and XRD result shows that the drug within the formulation was in the amorphous state. From the SEM analysis, the texture of powder showed a uniform granular structure, and there was no incompatibility between drugs. Excipients was observed from ftir study. From the in vitro dissolution study, it improved the dissolution rate of nifedipine, which was 98.68% of drug release, where pure drug release only 6.75%.

Enhanced oral bioavailability and anti-diabetic activity of canagliflozin through a spray dried lipid based oral delivery: a novel paradigm.

Canagliflozin (CFZ), a novel SGLT II antagonist, exhibits erratic absorption after oral administration. The current study entails development and evaluation of spray dried lipid based formulation (solid SMEDDS) for enhancing oral bioavailability and anti-diabetic activity of CFZ. Solid SMEDDS developed through spray drying containing Neusilin US2 as an adsorbent. The formed solid SMEDDS were characterized for physicochemical and solid state attributes. Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) were used to confirm the spherical morphology. In vitro dissolution, ex vivo permeability and in vivo pharmacokinetic studies were conducted to determine the release rate, permeation rate and absorption profile of CFZ, respectively. Pharmacodynamic studies were done as per standard protocols. The optimized solid SMEDDS exhibited acceptable practical yield and flow properties and is vouched with enhanced amorphization, nanoparticulate distribution and acceptable drug content. The spherical morphology of solid SMEDDS and reconstituted SMEDDS were confirmed in SEM and TEM, respectively. In vitro dissolution studies revealed multi-fold release behavior in CFZ in various dissolution media, whereas, remarkable permeability was observed in jejunum segment of rat intestine. Pharmacokinetic studies of CFZ in solid SMEDDS demonstrated 2.53 and 1.43 fold enhancement in Cmax and 2.73 and 1.98 fold in AUC 0-24h, as compared to pure API and marketed formulation, respectively. Pharmacological evaluation of solid SMEDDS revealed enhanced anti-diabetic activity of CFZ through predominant SGLT II inhibition in rats, as evident from evaluation of biochemical levels, urinary glucose excretion studies and SGLT II expression analysis. The current work describes significant improvement biopharmaceutical properties of CFZ in solid SMEDD formulation. Graphical abstract Graphical Abstract: Enhanced oral bioavailability and anti-diabetic activity of canagliflozin through a spray dried lipid based oral delivery: a novel paradigm.

Design and Evaluation of Telmisartan SMEDDS for Enhancing Solubility and Dissolution Rate

Telmisartan belongs to a BCS class II drug i.e. low solubility and high permeability. It is an angiotensin II type-I receptor blocker essentially used for the treatment and curing of hypertension. The critical problem facing with telmisartan as it shows low solubility in biological fluids which results into less bioavailability after oral administration. The aim of the present work is to enhance the solubility, dissolution rate of telmisartan by formulating an optimal SMEDDS formulation. SMEDDS were prepared by admixing method using Peceol and Captex 200 as oil phases. Labrafil M2125 as surfactant and Transcutol and plurololeique as co-surfactants. Later they obtained liquid SMEDDS were converted in to free flowing powder using adsorbent like Aerosil 200. All the SMEDDS formulations were found to be stable and they were further evaluated for physical parameters such as phase separation, particle size and drug content. The formulation CT1 with oil to co-surfactant ratio 1:1 respectively showed highest rate of dissolution than the other ratios. The drug, excipients and optimized formulation were subjected to characterization studies such as FTIR and DSC studies shown that there were no interactions between drug and excipients used.

Preparation of self micro emulsifying drug delivery system(smedds) of poorly soluble drug eprosartan mesylate and its in vitro evaluation

Eprosartan Mesylate (EM), an angiotensin II receptor blocker used in the treatment of high blood pressure. But poor solubility and bioavailability (13%) of eprosartan mesylate is a major challenging factor for improving its drug release rate. The main objective of the present work to develop and characterize self micro emulsifying drug delivery system of eprosartan mesylate by using compatible oil, surfactant and co-surfactant. For the selection of oil, surfactant and cosurfactant, solubility screening studies has been carried out. The nine formulations are prepared using peppermint oil, tween 80 and PEG 400. A pseudo ternary phase diagram was prepared to determine the self emulsion region. Four optimized formulations were prepared at 1:1 ratio(a mixture of surfactant and cosurfactant). These four formulations were evaluated for self-emulsification time, droplet size measurement, drug content analysis robustness to dilution test, viscosity analysis, f.t.i.r. The study and in-vitro diffusion studies. The ratio of scosmix (a mixture of surfactant and cosurfactant) of optimized formulation (pf5) was varied to pfa1 (2:1), pf2 (3:1), pfa3 (1:2) and compared with pure drug. The formulation having pfa1 (2:1) shown drug release of 93.13 % in 330 minutes where as pure drug showed a drug release of 54.51% in 330 minutes. So the prepared SMEDDS formulations were efficient and better than the pure drug, and it followed Korsmeyer pappes due to highest r2 value followed by Hixon crowel. It was concluded that incorporation of eprosartan mesylate in selfmicroemulsifying system is a great potential for improving the solubility and dissolution rate of eprosartan mesylate.

Solidification of carvedilol loaded SMEDDS by swirling fluidized bed pellet coating

Self-(micro)emulsifying drug delivery systems (S(M)EDDS) have emerged as effective vehicles for enhancing bioavailability of poorly water soluble drugs, however solidification of the systems represents a major challenge. Objective of this study was development of carvedilol loaded liquid SMEDDS and transformation into solid pellets employing fluid-bed coating technologies. Carvedilol-loaded formulation of SMEDDS was comprised of Capmul® MCM EP, castor oil, Kolliphor® RH40 and PEG 400. The obtained liquid SMEDDS mixed with fillers and polymers was layered onto MCC pellets. Coating process was conducted in the modified, swirl-flow based fluid bed coating device, which was proved superior over the conventional Wurster fluid bed, with lower agglomeration rate. Use of polymer was essential for entrapping SMEDDS in the coating layer(s). Self-microemulsifying properties as well as fast drug release as one of main SMEDDS advantages were preserved in the solid products. Addition of lactose into the coating dispersion and applying intermediate and surface film coating to the pellets enabled higher drug loading and prevented sticking of the pellets during handling and storage. Present study indicates that the (swirling) fluid-bed pellet coating technology is a promising strategy for preparation of solid SMEDDS-coated pellets with adequate drug loading capacity and enhanced release of poorly water soluble drug.

Design and development of a self-microemulsifying drug delivery system of olmesartan medoxomil for enhanced bioavailability

Olmesartan medoxomil (OM) is a hydrophobic antihypertensive drug with low bioavailability (26%) and is known to have adverse effects such as celiac disease and enteropathy. The purpose of this study was to develop SMEDDS to increase bioavailability and decrease potential side effects of OM. Hydrophilic lipophilic balance was calculated by testing solubility of OM in different oils, surfactants, and cosurfactants to obtain the most suitable combination of SMEDDS. Pseudoternary phase diagram was used to select the better oil/water formulation of SMEDDS. After a test for 3-month stability, dissolution tests and parallel artificial membrane permeability assay (PAMPA) were conducted to investigate drug solubility and permeability. Biodistribution of fluorescent marked SMEDDS was observed by using in vivo imaging system. The pharmacodynamics of the drug were determined by measuring blood pressure from tails of rats. At the end of the experiment, intestines were examined for adverse effects of OM. Compared with tablet formulation according to the dissolution study, SMEDDS formulation showed 1.67 times improvement in solubility of OM. PAMPA studies suggested a much faster permeability rate for OM SMEDDS compared to the suspension form. Labeled SMEDDS gave 3.96 times stronger fluorescent emission than control dye administered mice in in vivo imaging system (IVIS®) studies, indicating an increased bioavailability. Treating effect of SMEDDS was 3.1 times more efficient compared to suspension in hypertensive rats. It caused neither celiac-like enteropathy nor diarrhea, during 21-day noninvasive blood pressure system (NIBP) assay. Our results suggest that SMEEDS formulation improves dissolution and oral bioavailability of OM while reducing its adverse effects.