Oral formulations for highly lipophilic drugs: Impact of surface decoration on the efficacy of self-emulsifying drug delivery systems.

AIM: To evaluate the impact of the surface decoration of cannabidiol (CBD) loaded self-emulsifying drug delivery systems (SEDDS) on the efficacy of the formulations to cross the various barriers faced by orally administered drugs. METHODS: Polyethylene glycol (PEG)-free polyglycerol (PG)-based SEDDS, mixed zwitterionic phosphatidyl choline (PC)/PEG-containing SEDDS and PEG-based SEDDS were compared regarding stability against lipid degrading enzymes, surface properties, permeation across porcine mucus, cellular uptake and cytocompatibility. RESULTS: SEDDS with a size of about 200 nm with narrow size distributions were developed and loaded with 20-21 % of CBD. For PG containing PEG-free SEDDS increased degradation by lipid degrading enzymes was observed compared to PEG-containing formulations. The surface hydrophobicity of placebo SEDDS increased in the order of PG-based to mixed PC/PEG-based to PEG-based SEDDS. The influence of this surface hydrophobicity was also observed on the ability of the SEDDS to cross the mucus gel layer where highest mucus permeation was achieved for most hydrophobic PEG-based SEDDS. Highest cellular internalization was observed for PEG-based Lumogen Yellow (LY) loaded SEDDS with 92 % in Caco-2 cells compared to only 30 % for mixed PC/PEG-based SEDDS and 1 % for PG-based SEDDS, leading to a 100-fold improvement in cellular uptake for SEDDS having highest surface hydrophobicity. For cytocompatibility all developed placebo SEDDS showed similar results with a cell survival of above 75 % for concentrations below 0.05 % on Caco-2 cells. CONCLUSION: Higher surface hydrophobicity of SEDDS to orally deliver lipophilic drugs as CBD seems to be a promising approach to increase the intracellular drug concentration by an enhanced permeation through the mucus layer and cellular internalization.

Formulation Development and Evaluation of Cannabidiol Hot-Melt Extruded Solid Self-Emulsifying Drug Delivery System for Oral Applications.

Cannabidiol (CBD) is a highly lipophilic compound with poor oral bioavailability, due to poor aqueous solubility and extensive pre-systemic metabolism. The aim of this study was to explore the potential of employing Hot Melt Extrusion (HME) technology for the continuous production of Self Emulsifying Drug Delivery Systems (SEDDS) to improve the solubility and in vitro dissolution performance of CBD. Accordingly, different placebos were processed through HME in order to obtain a lead CBD loaded solid SEDDS. Two SEDDS were prepared with sesame oil, Poloxamer 188, Gelucire®59/14, PEO N80 and Soluplus®. Moreover, Vitamin E was added as an antioxidant. The SEDDS formulations demonstrated emulsification times of 9.19 and 9.30 min for F1 and F2 respectively. The formed emulsions showed smaller droplet size ranging from 150-400 nm that could improve lymphatic uptake of CBD and reduce first pass metabolism. Both formulations showed significantly faster in vitro dissolution rate (90% for F1 and 83% for F2) compared to 14% for the pure CBD within the first hour, giving an enhanced release profile. The formulations were tested for stability over a 60-day time period at 4°C, 25°C, and 40°C. Formulation F1 was stable over the 60-day time-period at 4°C. Therefore, the continuous HME technology could replace conventional methods for processing SEDDS and improve the oral delivery of CBD for better therapeutic outcomes.

Harnessing therapeutic deep eutectic solvents in self-emulsifying systems to improve CBD delivery.

In this study, Cannabidiol crystals (CBD) were used as a BCS class II model drug to generate a novel therapeutic deep eutectic solvent (THEDES) with easy preparation using caprylic acid (CA). The hydrogen bonding interaction was confirmed by different techniques such as FT-IR and NMR, resulting in a hydrophobic system suitable for liquid formulations. The CBD-based THEDES, combined with a specific mixture of surfactants and co-surfactants, successfully formed a self-emulsifying drug delivery system (SEDDS) that generated uniform nano-sized droplets once dispersed in water. Hence, the THEDES showed compatibility with the self-emulsifying approach, offering an alternative method to load drugs at their therapeutic dosage. Physical stability concerns regarding the unconventional oily phase were addressed through stress tests using multiple and dynamic light scattering, demonstrating the robustness of the system. In addition, the formulated SEDDS proved effective in protecting CBD from the harsh acidic gastric environment for up to 2 h at pH 1.2. Furthermore, in vitro studies have confirmed the safety of the formulation and the ability of CBD to permeate Caco-2 cells when formulated. This investigation highlights the potential incorporation of THEDES in lipid-based formulations like SEDDS, expanding the avenues for innovative oral drug delivery approaches.

Self Emulsifying Delivery System of Cissus quadrangularis: Evidence of Enhanced Efficacy and Promising Pharmacokinetic Profile in the Management of Osteoporosis.

Treatment therapies used to manage osteoporosis are associated with severe side effects. So worldwide herbs are widely studied to develop alternative safe & effective treatments. Cissus quadrangularis (CQ) has a significant role in bone health and fracture healing. It is documented that its extracts increase osteoblastic differentiation & mineralization. Currently, Cissus quadrangularis is available in the form of tablets in the market for oral delivery. But these conventional forms are associated with poor bioavailability. There is a need for a novel drug delivery system with improving oral bioavailability. Therefore, a Cissus quadrangularis-loaded self-emulsifying drug delivery system (CQ-SEDDS) was developed which disperses rapidly in the gastrointestinal fluids, yielding nano-emulsions containing a solubilized drug. This solubilized form of the drug can be easily absorbed through lymphatic pathways and bypass the hepatic first-pass effect. The emulsification efficiency, zeta potential, globule size, in-vitro dissolution, ex-vivo, in-vivo and bone marker studies were performed to assess the absorption and permeation potential of CQ incorporated in SEDDS. CQ-SEDDS with excipients Tween 80, Cremophor RH40, Transcutol HP & α-Tocopherol acetate had shown about 76% enhancement in the bioavailability of active constituents of CQ. This study provided the pre-clinical data of CQ-SEDDS using osteoporotic rat model studies.

Solid self-emulsifying casein carrier for the improvement on the oral bioavailability of simvastatin.

Simvastatin (SV) is a statin drug that can effectively control cholesterol and prevent cardiovascular diseases. However, SV is water-insoluble, and poor oral bioavailability (<5 %). Solid self-emulsifying carrier system is more stable than liquid emulsions, facilitating to improve the solubility and bioavailability of poorly soluble drugs. In the present study, a solid self-emulsifying carrier stabilized by casein (Cas-SSE) was successfully used to load SV to improve its solubility in water, by formulation selection and emulsification process optimization. Compared with oral tablets, the release of SV from Cas-SSE was significantly enhanced in artificial intestinal fluid. Furthermore, everted gut sac experiments indicated some water-soluble dispersing agents such as hydroxyethyl starch (HES), were not conducive to drug absorption. Pharmacokinetic studies suggested Cas-SSE without dispersing agent has much higher relative bioavailability (184.1 % of SV and 284.5 % of simvastatin acid) than SV tablet. The present work suggests Cas-SSE is a promising drug delivery platform with good biocompatibility for improving oral bioavailability of poorly water-soluble drugs.

Solubility of Poorly Soluble Drugs in Phosphatidylcholine-Based Drug Delivery Systems: Comparison of the Loading Capacity in the Bulk Formulation and Its Dispersed State.

The aim of this study was to determine the drug loading capacity of phosphatidylcholine-based formulations for four poorly water-soluble drug substances (clofazimine, fenofibrate, artemether, cannabidiol). Two self-dispersing lipid formulations were investigated, which consisted of soybean phospholipids, medium-chain triglycerides and ethanol with a different phospholipid-oil ratio. The direct loading of the bulk formulation was conducted with dual centrifugation, which proved to be a suitable method for screening experiments with the highly viscous formulations. To estimate possible precipitation after dispersion in the gastrointestinal fluids, the solubility of the drugs was investigated in the dispersed formulations. For this purpose, nanodispersions were prepared from the bulk formulations via high pressure homogenization and subsequently subjected to passive loading. A newly developed HPLC method with Charged Aerosol Detection allowed a simultaneous evaluation of the content of soybean lecithin and medium-chain triglycerides in the nanodispersions. When comparing the two phosphatidylcholine-based formulations, a high content of oil was advantageous with regard to a high loading capacity. Drug substances with melting points below 150 °C exhibited a high solubility in the phospholipid-based formulations. A surprisingly high solubility was observed for artemether and cannabidiol with up to 13.0% and 33.3% drug loaded to the formulations, respectively. In the dispersions, a similar solubility as in the bulk formulations was obtained for fenofibrate and cannabidiol. Clofazimine yielded a higher loading result in the nanodispersions than in the bulk formulation.

Zeta potential changing self-nanoemulsifying drug delivery systems: A newfangled approach for enhancing oral bioavailability of poorly soluble drugs.

The mucus is a defensive barrier for different drug-loaded systems. To overcome this obstacle, the crucial factor is the surface charge. Due to mucus negative charge behavior; it was revealed that negatively charged formulations can move across mucus, whereas positively charged nanoformulations could not diffuse via mucus due to interactions. However, cellular intake of negatively charged nanoformulations to the epithelium by endocytosis is less prominent as compared to positively charged carriers. Self-emulsifying drug delivery systems (SEDDS) improve the drug permeability of drugs, especially which have poor oral drug solubility. Moreover, SEDDS have the ability to reduce the degradation of drugs in the GI tract. Currently, drug carrier systems that can shift zeta potential from negative to positive were developed. The benefits of inducing zeta potential changing approach are that negatively charged nanoformulations permeate quickly across the mucus and surface charges reversed to positive at epithelium surface to increase cellular uptake. Among various systems of drug delivery, zeta potential changing SEDDS seem to signify a promising approach as they can promptly diffuse over mucus due to their smaller size and shape distortion ability. Due to such findings, mucus permeation and drug diffusion may improve by the mixture of the zeta potential changing approach and SEDDS.

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 lipid-based SEDDS using digestion products of long-chain triglyceride for high drug solubility: Formulation and dispersion testing.

A self-emulsifying drug delivery system (SEDDS) containing long chain lipid digestion products (LDP) and surfactants was developed to increase solubility of two model weakly basic drugs, cinnarizine and ritonavir, in the formulation. A 1:1.2 w/w mixture of glyceryl monooleate (Capmul GMO-50; Abitec) and oleic acid was used as the digestion product, and a 1:1 w/w mixture of Tween 80 and Cremophor EL was the surfactant used. The ratio between LDP and surfactant was 1:1 w/w. Since the commercially available Capmul GMO-50 is not pure monoglyceride and contained di-and-triglycerides, the digestion product used would provide 1:2 stoichiometric molar ratio of monoglyceride and fatty acid after complete digestion in gastrointestinal fluid. Both cinnarizine and ritonavir had much higher solubility in oleic acid (536 and 72 mg/g, respectively) than that in glyceryl monooleate and glyceryl trioleate. Therefore, by incorporating oleic acid in place of glyceryl trioleate in the formulation, the solubility of cinnarizine and ritonavir could be increased by 5-fold and 3.5-fold, respectively, as compared to a formulation without the fatty acid. The formulation dispersed readily in aqueous media, and adding 3 mM sodium taurocholate, which is generally present in GI fluid, remarkably improved the dispersibility of SEDDS and reduced particle size of dispersions. Thus, the use of digestion products of long-chain triglycerides as components of SEDDS can enhance the drug loading of weakly basic compounds and increase dispersibility in GI fluids.

Overcoming Solubility Challenges: Self-emulsifying Systems for Enhancing the Delivery of Poorly Water-Soluble Antiviral Drugs.

The primary goal of drug formulation is to improve a drug's bioavailability in the body. However, poorly water-soluble drugs present challenging issues related to their solubility and bioavailability factors. Emerging technologies, such as lipid-based drug delivery systems, including micro- or nanoemulsifying drug delivery systems, have become increasingly relevant to address the above challenges. This review presents a thorough overview of self-emulsifying drug delivery systems (SEDDS). It covers the properties, principles, self-emulsification mechanism, formulation strategies, and characterization methods of SEDDS. This review also addresses the delivery of antiviral agents through SEDDS. Moreover, it summarizes the marketed formulations of SEDDS consisting of antiviral agents. This review offers a comprehensive and valuable resource for future perspectives on SEDDS and their potential applications in antiviral drug delivery.

Diseño y caracterización de un sistema de entrega de fármacos autoemulsificable (SEDDS) de estradiol por diagramas de fases pseudoternarios y pruebas fisicoquímicas

Introducción: el estradiol es una hormona esteroide sexual femenina usada ampliamente como terapia hormonal que presenta una baja biodisponibilidad, debido a su baja solubilidad acuosa y a su alta hidrofobicidad, perteneciendo a la clase II del sistema de clasificación de biofarmacéutica. Objetivos: diseñar y caracterizar un sistema de entrega de fármacos autoemulsificable (SEDDS) para el fármaco estradiol por pruebas fisicoquímicas con el fin de obtener la relación óptima que permitiera mejorar su solubilidad acuosa, velocidad de disolución y potencialmente su biodisponibilidad. Método: estudios de solubilidad en diferentes solventes, diagramas de fases pseudoternarios constituidos por aceites, tensioactivos, cotensioactivos y agua permitieron reconocer las diferentes regiones de formación de SEDDS e identificar los porcentajes de excipientes que conducen a la formación de soluciones isotrópicas; las formulaciones resultantes fueron caracterizadas en tiempo de autoemulsificación, robustez a la dilución, punto de nube y perfil de disolución en capsula dura. Resultados: las formulaciones que contenían Capmul MCM®, Kolliphor® RH40 y Transcutol®, tuvieron un tiempo de autoemulsificación de aproximadamente 1 min; fueron estables en tres distintos pH (1,2; 4,5 y 7,2), en diferentes volúmenes de dilución, exhibiendo una apariencia transparente, ligeramente azulada, sin precipitados, o separación de fases, puntos de nube mayores en comparación de las formulaciones que contenían Gelucire® 44/14. Conclusiones: las estrategias de caracterización empleadas en el desarrollo de esta investigación demostraron ser eficientes para la selección adecuada de excipientes y su proporción óptima para el diseño eficaz de un sistema de entrega de fármaco autoemulsificable (SEDDS).

SUMMARY Introduction: Estradiol is a female sex steroid hormone widely used as hormonal therapy that has low bioavailability, due to its low aqueous solubility and high hydro-phobicity, belonging to class II of the Biopharmaceutical Classification System. Aim: To design and characterize a self-emulsifying drug delivery system (SEDDS) for the drug estradiol by physicochemical tests to obtain the most optimal ratio that would improve its aqueous solubility, dissolution rate, and potentially its bioavailability. Method: Solubility studies in different solvents; pseudo ternary phase diagrams made up of oils, surfactants, co-surfactants, and water, allowed to recognize the different regions of SEDDS formation and identify the percentages of excipients that lead to the formation of isotropic solutions; The resulting formulations were characterized in autoemulsification time, robustness to dilution, cloud point and dissolution profile in a hard capsule. Results: The formulations containing Capmul MCM®, Kolliphor® RH40, and Transcutol®, had an autoemulsification time of approximately 1 minute; were stable at three different pHs (1.2, 4.5 and 7.2), at different dilution volumes, exhibiting a transparent, slightly bluish appearance, without precipitates, or phase separation, higher cloud points compared to the formulations containing Gelucire® 44/14. Conclusions: The characterization strategies used in the development of this research proved to be efficient for the adequate selection of excipients and their optimal ratio for the effective design of a self-emulsifying drug delivery system (SEDDS).

Introdução: o estradiol é um hormônio esteroide sexual feminino amplamente utilizado como terapia hormonal que apresenta baixa biodisponibilidade devido à sua baixa solubilidade aquosa e alta hidrofobicidade, pertencente à classe II do sistema de classificação biofarmacêutica. Objetivos: projetar e caracterizar um sistema de liberação de drogas autoemulsificante (SEDDS) para o fármaco estradiol por meio de testes físico-químicos a fim de obter a proporção ideal que melhore sua solubilidade aquosa, taxa de dissolução e potencialmente sua biodisponibilidade. Método: estudos de solubilidade em diferentes solventes, diagramas de fases pseudoternários compostos por óleos, tensoativos, cotensoativos e água permitiram reconhecer as diferentes regiões de formação de SEDDS e identificar as porcentagens de excipientes que levam à formação de soluções isotrópicas; as formulações resultantes foram caracterizadas quanto ao tempo de autoemulsificação, robustez à diluição, ponto de turvação e perfil de dissolução da cápsula dura. Resultados: as formulações contendo Capmul MCM®, Kolliphor® RH40 e Transcutol®, tiveram um tempo de autoemulsificação de aproximadamente 1 min; foram estáveis em três diferentes pH's (1,2; 4,5 e 7,2), em diferentes volumes de diluição, apresentando aspecto transparente, levemente azulado, sem precipitados ou separação de fases, pontos de turvação mais elevados em relação às formulações contendo Gelucire® 44/14. Conclusões: as estratégias de caracterização utilizadas no desenvolvimento desta pesquisa mostraram-se eficientes para a seleção adequada de excipientes e sua proporção ideal para o desenho eficaz de um sistema de liberação de fármacos autoemulsificante (SEDDS).

Integrated

The drug formulation design of self-emulsifying drug delivery systems (SEDDS) often requires numerous experiments, which are time- and money-consuming. This research aimed to rationally design the SEDDS formulation by the integrated computational and experimental approaches. 4495 SEDDS formulation datasets were collected to predict the pseudo-ternary phase diagram by the machine learning methods. Random forest (RF) showed the best prediction performance with 91.3% for accuracy, 92.0% for sensitivity and 90.7% for specificity in 5-fold cross-validation. The pseudo-ternary phase diagrams of meloxicam SEDDS were experimentally developed to validate the RF prediction model and achieved an excellent prediction accuracy (89.51%). The central composite design (CCD) was used to screen the best ratio of oil-surfactant-cosurfactant. Finally, molecular dynamic (MD) simulation was used to investigate the molecular interaction between excipients and drugs, which revealed the diffusion behavior in water and the role of cosurfactants. In conclusion, this research combined machine learning, central composite design, molecular modeling and experimental approaches for rational SEDDS formulation design. The integrated computer methodology can decrease traditional drug formulation design works and bring new ideas for future drug formulation design.

Diseño y desarrollo de un sistema de entrega de fármaco autoemulsificable líquido de ibuprofeno incorporado por el método de adsorción por portador en una forma farmacéutica sólida (comprimidos) / Design and development of a liquids self emulsyfing drug delivery system of ibuprofen incorporated by the method adsorption by carriers in solids dosage forms

RESUMEN El ibuprofeno es uno de los fármacos más utilizados e indicado para terapias antiinflamatorias, dolor, entre otras patologías. Sin embargo, este fármaco presenta una baja y errática biodisponibilidad, debido a la pobre solubilidad acuosa intrínseca del mismo, por lo cual esta categorizado como clase II en el sistema de clasificación biofarmacéutica. El objetivo de este trabajo fue desarrollar, diseñar y evaluar un sistema de entrega de fármaco autoemulsificable (SEDDS) para mejorar la solubilidad y velocidad de disolución de ibuprofeno. Aceites, cosolventes, tensioactivos y portadores porosos fueron evaluados por su capacidad de mejorar la solubilidad del ibuprofeno, habilidad de autoemulsificación, robustez en diferentes pH y capacidad de adsorción. El aceite de coco, Tween 80 y propilenglicol lograron un aumento significativo de la solubilidad acuosa del ibuprofeno en un tiempo de autoemulsificación menor a 2 minutos. Neusilin US2® fue seleccionado como portador, dando como resultado un pequeño granulo de excelente fluidez, que permitió obtener comprimidos que cumplieron satisfactoriamente las pruebas de control de acuerdo con las especificaciones establecidas. Los SEDDS líquidos y sólidos son una alternativa de formulación ventajosa y prometedora para mejorar la solubilidad de fármacos pobremente solubles de acuerdo al sistema de clasificación biofarmacéutica, a través de sus propiedades de solubilización.

SUMMARY Ibuprofen is one of the most used drugs and it's indicated for anti-inflammatory therapies and pain, among other pathologies. However, this drug has a low and erratic bioavailability, due to its poor aqueous intrinsic solubility, which is categorized as class II in the Biopharmaceutical Classification System. The objective of this work was to develop, design and evaluate a self-emulsifying drug delivery system (SEDDS) to improve the solubility and dissolution rate of ibuprofen. Oils, co-solvents, surfactants and carriers were evaluated for their ability to improve the solubility of ibuprofen, self-emulsification ability, robustness at different pH levels and adsorption capacity. Coconut oil, Tween 80 and propylene glycol achieved a significant increase in the aqueous solubility of ibuprofen in a self-emulsification time of less than 2 minutes. Neusilin US2® was selected as carrier, resulting in a small granule of excellent fluidity, which allowed to obtain tablets that satisfactorily fulfilled the control tests according to the established specifications. The liquid and solid SEDDS are an advantageous and promising formulation alternative to improve the solubility of poorly soluble drugs according to the biopharmaceutical classification system, through their solubilization properties.

Formulation optimization, in situ intestinal absorption and permeability of psoralen and isopsoralen / 中草药·英文版

Objective: To optimize a self-emulsifying drug delivery system (SEDDS) formulation for psoralen and isopsoralen (PSO and IPSO) isolated from Psoraleae Fructus. Methods: A D-optimal design was used to investigate the influence of oil percentage, surfactant percentage and cosurfactant percentage on several properties of SEDDS including particle size, polydispersity, equilibrium solubility, in situ intestine absorption rate and intestinal permeability. Furthermore, the desirability function approach was applied to obtain the optimal formulation for the system. Results: The oil percentage, surfactant percentage and cosurfactant percentage were optimized to be 53.6%, 35.7% and 10.7%, respectively, which means the model is available. Conclusions: The D-optimal design is valuable to optimize the SEDDS formulation and understand formulation compositions’ functions on SEDDS properties.

Development of self-emulsifying drug delivery system for oxymatrine phospholipid complex / 中草药

Objective To prepare oxymatrine (OMT) phospholipid complex (PC) self-emulsifying drug delivery system (OMT-PC- SEDDS), and evaluate its quality and release in vitro. Methods The emulsifiers, co-emulsifiers and ratio of emulsifier to co-emulsifier (Km) were selected through the pseudo-ternary phase diagram method, using emulsified area as selection index, investigation of oil phase by solubility was determined to optimize the prescription. The appearance, average particle diameter, self-emulsification time, in vitro release characteristics, and stability of OMT-PC-SEDDS were evaluated. Results The optimum prescription of OMT-PC-SEDDS was emulsifier Kolliphor HS 15 and co-emulsifier ethanol mass ratio of 2:1, the mass ratio of medium chain triglyceride (MCT) to the total mass of Kolliphor HS 15 and ethanol was 2:8. The appearance of OMTPC-SEDDS was translucent clear liquid with good stability. OMT-PC-SEDDS diluted with water to form milky and pale blue emulsion. The emulsion was observed to be spherical by transmission electron microscopy and distributed evenly with average particle size of (355.00 ± 19.50) nm and Zeta potential of (-12.80 ± 0.66) mV. In pH 6.8 phosphate buffer, the in vitro release, the in vitro release of OMT, OMT-PC, and OMT-PC-SEDDS respectively reached 93.84%, 88.39%, and 88.61% at 4 h. Conclusion The prepared OMT-PC-SEDDS by optimum formulation of this study has a good particle size and good stability.

Preparation and quality evaluation of self-emulsifying drug delivery system of total saponins of Sanguisorba officinalis / 中草药

Objective: To optimize the formulation of the self-emulsifying drug delivery system of total saponins of Sanguisorba officinalis and evaluate its characteristics. Methods: The formulation and its proportion of the self-emulsifying drug delivery system of total saponins of S. officinalis were optimized based on the solubility tests, formula compatibility, microemulsion area in the ternary phase diagram and D-optimal mixing experiment design. The dosage of oil phase, surfactant and co-surfactant were investigated by drug loading, particle size, and polydispersity index. The appearance, particle size, polydispersity index, Zeta potential, and in vitro release of preparation were finally evaluated. Results: The ratio of oil phase, surfactant, and co-surfactant was 0.25: 0.45:0.30. The drug loading was 23.93 mg/g, the average particle size was (207.92 ± 2.13) nm and the zeta potential was (38.84 ± 0.18) mV. The release of SEDDS was superior to the bulk drug apparently. Conclusion: The self-emulsifying drug delivery system of total saponins of S. officinalis was established. The technology was feasible and the quality was stable.

Development of essential oil of Alpiniae zerumbet self-emulsifying drug release system / 中草药

Objective To optimize the formulation of essential oil of Alpiniae zerumbet self-emulsifying drug delivery system (EOFAZ-SEDDS) and evaluate its pharmacological properties. Methods The emulsifiers, co-emulsifiers and ratio of emulsifier to co-emulsifier (Km) were selected through the pseudo-ternary phase diagram method, using emulsified area as selection index, and determine the optimal prescription. The appearance, particle diameter, self-emulsification efficiency, and stability were evaluated. Results The optimal SEDDS was composed of volatile oil (60%), Kolliphor HS 15 (20%), and anhydrous ethanol (20%). The appearance of EOFAZ-SEDDS was translucent diluted-yellow solution. EOFAZ-SEDDS diluted with water to form milky and pale blue emulsion with a particle size of (171.67 ± 7.64) nm and Zeta potential of (-11.51 ± 1.22) mV. The emulsion was observed to be spherical by transmission electron microscopy and distributed evenly. The self-emulsifying time of EOFAZ-SEDDS in hydrochloric acid (0.1 mol/L) was short. With the increase of the volume of medium, the self-emulsifying time was prolonged. The precipitation and delamination of EOFAZ-SEDDS were not observed within 24 h after self-emulsifying, and no stratification was observed after 30 min centrifugation. Conclusion The EOFAZ-SEDDS prepared by optimum formulationthe of this study has a good particle size and good stability.

Intestinal absorption characteristic of tanshinone components SEDDS using one-way intestinal perfusion in situ / 中草药

Objective: To explore the intestinal absorption characteristics of tanshinone components self emulsifying drug delivery system (SEDDS). Methods: In situ single-pass perfusion method was used to investigate the absorption characteristics of cryptonshinone, tanshinone I, and tanshinone IIA in rats. The absorption parameters (Ka, Papp) of cryptotanshinone, tanshinone I, and tanshinone IIA were used as indicators to study their optimum absorption site among duodenum, jejunum, ileum, and colon. The effects of verapamil hydrochloride (P-glycoprotein inhibitor, P-gp inhibitor), probenecid (multi-drug resistant protein MRP2), and 2, 4-dinitrophenol (energy inhibitor) on the absorption of cryptonshinone, tanshinone I, and tanshinone IIA were also studied, as well as the effects of their different concentration. Results: Cryptonshinone, tanshinone I, and tanshinone IIA could be absorbed at all four intestinal segments, and the optimum absorption site was the upper segment of small intestine. The absorption of cryptotanshinone and tanshinone I were concentration-dependent at experimental concentration levels (1.05-4.19 mg/L and 1.22-5.56 mg/L), while tanshinone IIA was not affected obviously by its concentrations (2.43-11.12 mg/L). Verapamil hydrochloride had no significant influence on the absorption of cryptotanshinone or tanshinone I, while the absorption of tanshinone IIA was improved remarkably. Probenecid increased the absorption of cryptonshinone and tanshinone I apparently, while had no obvious effect on that of tanshinone IIA. 2,4-Dinitrophenol could decrease the absorption of cryptonshinone, tanshinone I, and tanshinone IIA apparently. Conclusion: Cryptonshinone and tanshinone I are supposed to be the substrate of MRP2 instead of P-gp. Tanshinone IIA is supposed to be the substrate of P-gp, instead of MRP2. The energy participated in the absorption of cryptonshinone, tanshinone I, and tanshinone IIA. Active absorption maybe also involved in the absorption of cryptonshinone, tanshinone I, and tanshinone IIA.

Determination of Total Ginkgo Flavonoid in Self-emulsifying Drug Delivery System by HPLC / 中国药师

Objective:To develop an HPLC method for determining the total ginkgo flavonoid in self-emulsifying drug delivery sys-tem. Methods:Effective chromatographic separation was achieved using a phenomenex C18 column (250 mm × 4. 6 mm, 5 μm) with a mobile phase composed of methanol and water (0.4% phosphoric acid) with the ratio of 50 ∶50 (v/v). The mobile phase was pumped using an isocratic HPLC system at a flow rate of 1. 0 ml·min-1 , the detection wavelength was 360 nm and the column temper-ature was 30 ℃. Results:The three components in the total ginkgo flavonoid were well separated by the proposed method. The linear relationship between the peak area and the concentration was promising within the range of 2. 0-40. 0 μg·ml-1 for quercetin, 3. 0-60. 0 μg·ml-1 for kaempferide and 2. 0-40. 0 μg·ml-1 for isorhamnetin. The mean recovery of quercetin, kaempferide and isorham-netin was 98. 4%, 99. 7% and 100. 5% with RSD of 0. 92%,0. 62% and 1. 24% (n=9), respectively. Conclusion:The method is specific and stable in the determination of total ginkgo flavonoid in self-emulsifying drug delivery system.

Preparation and Characteristics of Self-Emulsifying Drug Delivery System of Total Ginkgo Flavonoid / 中国药师

Objective:To prepare total ginkgo flavonoid self-emulsifying drug delivery system(TGF-SMDDS)and estimate its char-acteristics in vitro. Methods:The formula of TGF-SMDDS was optimized based on the solubility tests,formula compatibility and microe-mulsion area in the pseudo ternary phase diagram. The appearance,morphology,particle size,zeta potential and in vitro dissolution of TGF-SMDDS were investigated. Results:The formula was composed of oleoyl macrogolglycerides as the oil phase,Tween-80 as the sur-factant and XCF as the co-surfactant. The ratio of oil phase,surfactant and co-surfactant was 10 ∶ 6 ∶ 4. The drug loading was 10. 0 mg· g -1 . After mixed with water,TGF-SMDDS was formed a clear and transparent microemulsion with homogeneous small spheres as seen un-der a transmission electron microscope. The particle size and zeta potential of TGF-SMDDS was(87. 4 ±26. 7)nm and( -13. 1 ±1. 5) mV,respectively. The accumulative dissolution of TGF-SMDDS in pH1. 2 hydrochloric acid solution was(96. 1 ±4. 8)% in 45 min. Con-clusion:The TGF-SMDDS can significantly enhance the dissolution of TGF in vitro,which may be a potential effective preparation for TGF.