RESUMEN
AIM: The present study endeavours to develop a solid self-microemulsifying nutraceutical drug delivery system for hesperidin (HES) using quality by design (QbD) to improve its biopharmaceutical attributes. METHODS: A 32 full factorial design was employed to study the influence of factors on selected responses. Risk assessment was performed by portraying Ishikawa fishbone diagram and failure mode effect analysis (FMEA). The in vivo antidiabetic study was carried on induced diabetic rats. RESULTS: The optimised liquid SMEDDS-HES (OF) formulation showed emulsification time (Y 1) = 102.5 ± 2.52 s, globule size (Y 2) = 225.2 ± 3.40 nm, polydispersity index (Y 3) = 0.294 ± 0.62, and zeta potential (Y 4) = -25.4 ± 1.74 mV, respectively. The solid SMEDDS-HES (SOF-7) formulation was characterised by FTIR, PXRD, DSC, and SEM. The shelf life of SOF-7 was found to be 32.88 months. The heamatological and histopathological data of diabetic rats showed prominent antidiabetic activity. CONCLUSIONS: The optimised formulation showed improved dissolution, desired stability, and promising antidiabetic activity.
Asunto(s)
Productos Biológicos/administración & dosificación , Suplementos Dietéticos , Emulsionantes/administración & dosificación , Hesperidina/administración & dosificación , Adsorción , Animales , Rastreo Diferencial de Calorimetría , Química Farmacéutica/métodos , Sistemas de Liberación de Medicamentos , Emulsiones , Excipientes , Hipoglucemiantes , Técnicas In Vitro , Masculino , Modelos Estadísticos , Páncreas/efectos de los fármacos , Páncreas/patología , Ratas , Ratas Wistar , Reproducibilidad de los Resultados , Medición de Riesgo , Solubilidad , Tensoactivos , Termodinámica , Difracción de Rayos XRESUMEN
The objective of our study was to determine the effects of abomasal infusion of an emulsifier on fatty acid (FA) digestibility and production responses of lactating dairy cows. Eight rumen-cannulated cows (109 ± 18 d in milk) were randomly assigned to a treatment sequence in replicated 4 × 4 Latin squares with 18-d periods including 7 d of washout and 11 d of infusion with sampling on the last 4 d. Treatments were abomasal infusions of water carrier only (CON) and 3 levels of increasing doses of Tween 80 (polysorbate 80, Tween 80, Sigma-Aldrich, St. Louis, MO) delivering 15 (D-15), 30 (D-30), and 45 (D-45) g/d. The Tween 80 was dissolved in water before infusions, which were delivered at 6-h intervals. Cows were fed the same diet, which contained (% dry matter) 31% neutral detergent fiber, 17% crude protein, 25% starch, and 4% FA (2% dry matter from a saturated fat supplement containing 33% C16:0 and 51% C18:0). Increasing emulsifier infusion dose quadratically increased digestibility of total FA (60.7, 65.3, 70.9, and 66.8%), 16-carbon FA (61.7, 63.9, 70.4, and 66.7%), and 18-carbon FA (59.8, 65.6, 71.1, and 66.6%, respectively). Increasing emulsifier infusion dose quadratically increased absorbed total FA (625, 670, 744, and 658 g/d), 16-carbon FA (151, 157, 197, and 157 g/d, quadratic), and 18-carbon FA (420, 460, 500, and 444 g/d). Increasing emulsifier infusion dose tended to quadratically decrease dry matter intake (29.0, 28.8, 29.6, and 27.6 kg/d). Increasing emulsifier infusion dose quadratically increased milk fat content (3.23, 3.35, 3.45, and 3.35%), milk fat yield (1.54, 1.61, 1.65, and 1.55 kg/d), ECM (45.7, 46.9, 47.5, and 45.3 kg/d), and plasma nonesterified fatty acid concentration (95.6, 98.4, 101.2, and 98.6 µEq/L). On a yield basis, we observed that de novo, mixed, and preformed FA responded quadratically to Tween 80 infusion due to FA yield increasing up to D-30. Treatments had no effect on milk yield (47.9, 48.3, 48.0, and 46.6 kg/d). In conclusion, short-term infusion of an exogenous emulsifier improved FA digestibility and milk fat yield responses when cows were fed a diet containing a saturated fat supplement. Most digestion and production measurements responded quadratically because the highest dose of exogenous emulsifier (45 g/d) decreased dry matter intake and performance.
Asunto(s)
Abomaso , Alimentación Animal/análisis , Bovinos , Emulsionantes/administración & dosificación , Ácidos Grasos/metabolismo , Animales , Dieta/veterinaria , Fibras de la Dieta/metabolismo , Suplementos Dietéticos , Digestión/efectos de los fármacos , Emulsionantes/metabolismo , Femenino , Lactancia , Leche/metabolismo , Rumen/metabolismo , Almidón/metabolismoRESUMEN
Pentoxifylline (PTX), an anti-hemorrhage drug used in the treatment of intermittent claudication, is extensively metabolized by the liver resulting in a reduction of the therapeutic levels within a short duration of time. Self-nano-emulsifying drug delivery system (SNEDDS) is well reported to enhance the bio-absorption of drugs by forming nano-sized globules upon contact with the biological fluids after oral administration. The present study aimed to formulate, characterize, and improve the oral bioavailability of PTX using SNEDDS. The formulated SNEDDS consisted of palm oil, Capmul® MCM, and Tween® 80 as oil, surfactant, and co-surfactant, respectively. The mixture design module under the umbrella of the design of experiments was used for the optimization of SNEDDS. The dynamic light-scattering technique was used to confirm the formation of nanoemulsion based on the globule size, in addition to the turbidity measurements. In vivo bioavailability studies were carried out on male Wistar rats. The pharmacokinetic parameters upon oral administration were calculated using the GastroPlus software. The optimized SNEDDS had a mean globule size of 165 nm with minimal turbidity in an aqueous medium. Bioavailability of PTX increased 1.5-folds (AUC = 1013.30 ng h/mL) as SNEDDS than the pure drug with an AUC of 673.10 ng h/mL. In conclusion, SNEDDS was seen to enhance the bioavailability of PTX and can be explored to effectively control the incidents of intermittent claudication.
Asunto(s)
Caprilatos/farmacocinética , Sistemas de Liberación de Medicamentos/métodos , Emulsionantes/farmacocinética , Glicéridos/farmacocinética , Nanopartículas/metabolismo , Aceite de Palma/farmacocinética , Pentoxifilina/farmacocinética , Administración Oral , Animales , Disponibilidad Biológica , Caprilatos/administración & dosificación , Liberación de Fármacos , Emulsionantes/administración & dosificación , Glicéridos/administración & dosificación , Masculino , Nanopartículas/administración & dosificación , Aceite de Palma/administración & dosificación , Tamaño de la Partícula , Pentoxifilina/administración & dosificación , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/farmacocinética , Ratas , Ratas WistarAsunto(s)
Quimioexfoliación , Aceite de Crotón/efectos adversos , Composición de Medicamentos , Erupciones por Medicamentos/etiología , Emulsionantes/administración & dosificación , Fenol/efectos adversos , Animales , Aceite de Crotón/administración & dosificación , Erupciones por Medicamentos/patología , Fenol/administración & dosificación , PorcinosRESUMEN
This work studies the effect of enzymatic glycerolysis on digestibility and bioaccessibility of ratfish liver oil (RLO) rich in alkylglycerols (AKGs), as well as the capability of the glycerolysis product (GP) to act as lipid-based delivery system (LBDS) for a supercritical rosemary extract. For comparison purposes, digestibility and bioaccessibility of two additional lipid systems i.e. original RLO and RLO with addition of GRAS monoolein (MO) as emulsifier agent (RLO + MO), have been evaluated. We have studied the efficiency of the GP and RLO + MO lipid systems as LBDS by combining them with a supercritical rosemary extract (RE), i.e. RE lipid-based formulations. In vitro digestibility and bioaccessibility of un-loaded lipid systems, RE lipid-based formulations and un-carried RE have been determined. The results show a higher digestibility and bioaccessibility of the GP as compared to those of original RLO and RLO + MO. Likewise, a substantial improvement of RE bioaccessibility has been observed when GP is used as lipid carrier of RE. The present work demonstrates that enzymatic glycerolysis is an efficient strategy to obtain highly bioaccessible and potentially bioactive alkylglycerol-based delivery systems, which can be used to increase the bioaccessibility of low water-soluble bioactive compounds.
Asunto(s)
Digestión/efectos de los fármacos , Extractos Vegetales/farmacología , Rosmarinus , Disponibilidad Biológica , Sistemas de Liberación de Medicamentos , Emulsionantes/administración & dosificación , Humanos , Técnicas In Vitro , Extractos Vegetales/administración & dosificaciónRESUMEN
The objective of this study was to investigate the effects of diets supplemented with sodium stearoyl-2-lactylate (SSL), polyglycerol fatty acid ester (PGFE), and combined emulsifiers (0.02% SSL and 0.08% PGFE) on growth performance, nutrient digestibility, and plasma lipid profiles in weaned piglets and to further evaluate the possible effects of feeding exogenous emulsifiers on digestive enzyme activities and liver bile acid (BA) metabolism. Twenty-eight barrows (age at 35 d, Duroc × Landrace × Yorkshire) with an initial BW of 10.13 ± 0.16 kg were randomly assigned to 4 dietary treatment groups (7 pigs/treatment). Dietary treatment groups included the following: 1) basal diet (Control, CTR); 2) basal diet with 0.1% SSL (SSL); 3) basal diet with 0.1% PGFE (PGFE); and 4) basal diet with 0.08% PGFE+0.02% SSL (PG-SL). SSL diet increased ADG and ADFI of piglets during day 0 to 17 (P < 0.05) compared with the CTR treatment. Piglets fed emulsifier diets experienced a significant improvement in the digestibility of nutrients (DM, CP, ether extract, energy, calcium, and phosphorus) during the first 17 d (P < 0.05). The level of low-density lipoprotein cholesterol (LDL-C) was lower in the PGFE and PG-SL treatment groups than in the CTR treatment group (P < 0.05). Feeding emulsifier diets increased the lipase activity of the pancreas when compared with the CTR diet (P < 0.05). Moreover, the emulsifier diets significantly increased the mRNA expression of FXR (P < 0.05) and decreased the mRNA expression of CYP27A1 (P < 0.05) in the liver. In conclusion, the addition of emulsifiers improved nutrient digestibility and increased the mRNA expression of FXR BA receptors while inhibiting the mRNA expression of BA biosynthesis by CYP27A1 in weanling piglets.
Asunto(s)
Alimentación Animal/análisis , Suplementos Dietéticos/análisis , Ácidos Grasos/administración & dosificación , Estearatos/administración & dosificación , Porcinos/fisiología , Animales , Ácidos y Sales Biliares/metabolismo , Dieta/veterinaria , Digestión , Emulsionantes/administración & dosificación , Femenino , Masculino , Nutrientes , Distribución Aleatoria , Porcinos/crecimiento & desarrollo , DesteteRESUMEN
As constituents of cellular membranes, lecithins feature high biocompatibility and great emulsifying properties due to their amphiphilicity. Additionally, there are expectations that these naturally occurring emulsifying agents can replace other skin damaging emulsifiers like sodium dodecyl sulfate or sodium laureth sulfate. However, cytotoxicity data of lecithin-based formulations on primary human skin cells are scarce. Thus, we developed nanoemulsions with different kinds of surfactants (amphoteric, anionic and non-ionic), studied the skin permeation of a model drug from this formulations employing Franz-type diffusion cells and monitored their cytotoxicity potential on primary human keratinocytes and fibroblasts using a cell proliferation assay. The skin diffusion studies demonstrated that the amphoteric lecithin-based emulsifiers were superior to non-ionic surfactants in terms of skin permeation, but inferior to anionic emulsifiers. Further, we found that the nanoemulsions containing the amphoteric lecithins as emulsifying agents lead to significantly higher viability rates of both epidermal keratinocytes and dermal fibroblasts than the investigated anionic and non-ionic surfactants. This renders them a promising alternative to conventional emulsifiers used in daily products.
Asunto(s)
Emulsionantes/administración & dosificación , Fibroblastos/efectos de los fármacos , Queratinocitos/efectos de los fármacos , Lecitinas/administración & dosificación , Nanopartículas/administración & dosificación , Piel/metabolismo , Adulto , Anciano , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Emulsiones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Piel/citología , Absorción Cutánea , Porcinos , Adulto JovenRESUMEN
A 2-factor test design was used to investigate the effect of an emulsifier (Aldo®, Lonza, America) (200 g/t) in the diet of Cherry Valley meat ducks to replace some of 2 different oils (animal fat and vegetable oil) on meat production performance, slaughter traits, and fat metabolism. The 900 healthy 18-day-old ducks were grouped into 6 treatments, each with 5 replicates and 30 meat ducks per replicate. The 2 fat sources were established as a positive control group, a negative control group (positive control group-some oil (equivalent to metabolic energy of 50 kcal/ton)), and an emulsifier group (negative control group + 200 g/ton Aldo). The results showed that addition of different fat sources in feed had no significant effect on growth performance, carcass properties, and fat metabolism of 18- to 42-day-old meat ducks (P > 0.05). Reducing the amount of oil used in the feed lowered the growth performance, carcass properties, and affected fat metabolism of meat ducks. However, in feeds with 2 fat sources, some oils were replaced by adding Aldo without affecting growth performance and carcass properties of meat ducks, and improved their fat metabolism, reduced triglycerides (TG) in serum, and increased activity of lipoprotein and hepatic lipases in liver and of pancreatic lipase. Thus, addition of Aldo to a low fat diet could improve growth performance, carcass quality, and lipid metabolism, and promote digestion and absorption of fat for meat ducks.
Asunto(s)
Grasas de la Dieta/metabolismo , Patos/fisiología , Emulsionantes/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Carne/análisis , Alimentación Animal/análisis , Animales , Dieta/veterinaria , Grasas de la Dieta/administración & dosificación , Grasas de la Dieta/clasificación , Suplementos Dietéticos/análisis , Patos/crecimiento & desarrollo , Emulsionantes/administración & dosificación , Femenino , Masculino , Distribución AleatoriaRESUMEN
The present report demonstrates a quality by design approach to understand and optimize self-nanoemulsifying orodispersible films (SNEODF) of captopril for hypertension. A central composite experimental design was used to study the formulation parameters effects (primary emulsion, aqueous phase, and surfactant) on the film properties (globule size, film burst, adhesion, Young's moduli, disintegration time, tensile strength and dissolution). Principle component analysis (PCA) and principle component regression (PCR) were employed to identify and quantify the effects of formulation variables and physico-mechanical properties of the film on the drug permeability. PCA classified three distinct groups of film formulations based on their composition and properties. PCR quantified the impact of main variables, their interactions, and square effects on the drug permeability. The main effect of the aqueous phase exhibited a negative impact, while that of flux and tensile strength showed a positive impact on the permeability. Interactions of primary emulsions with disintegration time and tensile strength displayed a synergistic impact. Interactions of aqueous phase with flux, Young's moduli, and tensile strength, as well as between Young's moduli and tensile strength showed a significant positive effect on the permeability. A negative correlation of square effects of primary emulsion and flux, and a positive square effect of Young's moduli confirmed their non-linear influence on the drug permeability across porcine buccal mucosa. This research work demonstrates application of design of experiment and multivariate methods to achieve targeted product quality of captopril (SNEODF) having improved permeability and pH independent release profile.
Asunto(s)
Captopril/farmacocinética , Sistemas de Liberación de Medicamentos/métodos , Emulsionantes/farmacocinética , Mucosa Bucal/efectos de los fármacos , Absorción por la Mucosa Oral/efectos de los fármacos , Administración Oral , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/farmacocinética , Animales , Captopril/administración & dosificación , Evaluación Preclínica de Medicamentos/métodos , Emulsionantes/administración & dosificación , Mucosa Bucal/metabolismo , Análisis Multivariante , Absorción por la Mucosa Oral/fisiología , PorcinosRESUMEN
Poor aqueous solubility and low bioavailability are limiting factors in the oral delivery of lipophilic drugs. In a formulation approach to overcome these limitations, rice bran (RB) oil was evaluated as drug carrier in the development of self-nanoemulsifying drug delivery systems (SNEDDS). The performance of RB in formulations incorporating Kolliphor RH40 or Kolliphor EL as surfactants and Transcutol HP as cosolvent was compared to a common oil vehicle, corn oil (CO). Serial dilutions of the preconcentrates were performed in various media [distilled water and simulated intestinal fluids mimicking fasted state (FaSSIF) and fed state (FeSSIF)] and at different dilution ratios to simulate the in vivo droplets' behavior. The developed SNEDDS were assessed by means of phase separation, droplet size, polydispersity index, and ζ-potential. Complex ternary diagrams were constructed to identify compositions exhibiting monophasic behavior, droplet size < 100 nm, and polydispersity index (PDI) < 0.25. Multifactor analysis and response surface areas intended to determine the factors significantly affecting droplet size. The oil capacity to accommodate lipophilic drugs was assessed via fluorescence spectroscopy based on the solvatochromic behavior of Nile Red. Solubility studies were performed to prepare fenofibrate- and itraconazole-loaded SNEDDS and assess their droplet size, whereas dissolution experiments were conducted in simulated intestinal fluids. Caco-2 cell viability studies confirmed the safety of the SNEDDS formulations at 1:100 and 1:1000 dilutions after cell exposure in culture for 4 h. The obtained results showed similar performance between RB and CO supporting the potential of RB as oil vehicle for the effective oral delivery of lipophilic compounds.
Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Emulsionantes/química , Nanopartículas/química , Aceite de Salvado de Arroz/química , Disponibilidad Biológica , Células CACO-2 , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/química , Emulsionantes/administración & dosificación , Excipientes/administración & dosificación , Excipientes/química , Humanos , Nanopartículas/administración & dosificación , Tamaño de la Partícula , Aceite de Salvado de Arroz/administración & dosificación , Solubilidad , Tensoactivos/química , Agua/químicaRESUMEN
We prepared mineral oil-based emulsion adjuvants by employing simple self-emulsifying drug delivery system (SEDDS). Mineral oil emulsions (3%, 5%, and 7%) were prepared using deionized water and C-971P NF and C-940 grade carbomer solutions with concentrations 0.01% (w/v) and 0.02% (w/v). In total, 15 emulsions were prepared and mixed with a solution containing inactivated Mycoplasma hyopneumoniae (J101 strain) antigen and porcine circovirus type 2 antigen to prepare vaccines. Droplet sizes in the submicron range and zeta potential values between - 40 and 0 mV were maintained by most emulsion adjuvants for a period of 6 months. Emulsion adjuvants were regarded safe, and their M. hyopneumoniae-specific IgG, IgG1, and IgG2a titers were either better or comparable to those of aluminum gel.
Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Emulsionantes/toxicidad , Inmunoglobulina G/inmunología , Aceite Mineral/toxicidad , Mycoplasma hyopneumoniae/inmunología , Agua , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/toxicidad , Animales , Emulsionantes/administración & dosificación , Emulsiones/administración & dosificación , Emulsiones/toxicidad , Ratones , Ratones Endogámicos BALB C , Aceite Mineral/administración & dosificación , Mycoplasma hyopneumoniae/efectos de los fármacos , Porcinos , Agua/administración & dosificaciónRESUMEN
A self-nanoemulsifying drug delivery system (SNEDDS) was developed as a novel route to enhance the efficacy of docetaxel lipophilic drug. SNEDDS comprised ethyl oleate, Tween 80 and poly(ethylene glycol) 600, as oil, surfactant and co-surfactant, and formed stabilized monodispersed oil nanodroplets upon dilution in water. SNEDDS represented encapsulation efficiency and loading capacity of 21.4 and 52.7%, respectively. The docetaxel release profile from the drug-loaded SNEDDS was recorded, its effectiveness against MCF-7 cell line was investigated, and an IC50 value of 0.98 ± 0.05 µg mL-1 was attained. The drug-loaded SNEDDS was administrated in rats, and the pharmacokinetic parameters of maximum concentration of 22.2 ± 0.8 µg mL-1, time to attain this maximum concentration of 230 min, and area under the curve of 1.71 ± 0.18 µg min mL-1 were obtained. The developed SNEDDS formulation can be represented as an alternative to docetaxel administration.
Asunto(s)
Antineoplásicos/administración & dosificación , Supervivencia Celular/efectos de los fármacos , Docetaxel/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Emulsionantes/administración & dosificación , Animales , Antineoplásicos/farmacocinética , Supervivencia Celular/fisiología , Docetaxel/farmacocinética , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos/métodos , Emulsionantes/farmacocinética , Femenino , Humanos , Células MCF-7 , Ratas , Ratas Sprague-DawleyRESUMEN
Simvastatin (Sim) is a widely known drug in the treatment of hyperlipidemia, which has attracted so much attention in bone regeneration due to its potential osteoanabolic effect. However, repurposing of Sim in bone regeneration will require suitable delivery systems that can negate undesirable off-target/side effects. In this study, we have investigated a new lipid nanoparticle (NP) platform that was fabricated using a binary blend of emulsifying wax (Ewax) and glyceryl monooleate (GMO). Using the binary matrix materials, NPs loaded with Sim (0-500 µg/mL) were prepared and showed an average particle size of about 150 nm. NP size stability was dependent on Sim concentration loaded in NPs. The suitability of NPs prepared with the binary matrix materials in Sim delivery for potential application in bone regeneration was supported by biocompatibility in pre-osteoclastic and pre-osteoblastic cells. Additional data demonstrated that biofunctional Sim was released from NPs that facilitated differentiation of osteoblasts (cells that form bones) while inhibiting differentiation of osteoclasts (cells that resorb bones). The overall work demonstrated the preparation of NPs from Ewax/GMO blends and characterization to ascertain potential suitability in Sim delivery for bone regeneration. Additional studies on osteoblast and osteoclast functions are warranted to fully evaluate the efficacy of Sim-loaded Ewax/GMO NPs using in-vitro and in-vivo approaches.
Asunto(s)
Regeneración Ósea/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Emulsionantes/síntesis química , Glicéridos/síntesis química , Nanopartículas/química , Simvastatina/síntesis química , Animales , Regeneración Ósea/fisiología , Evaluación Preclínica de Medicamentos/métodos , Reposicionamiento de Medicamentos/métodos , Emulsionantes/administración & dosificación , Glicéridos/administración & dosificación , Ratones , Nanopartículas/administración & dosificación , Osteoblastos/efectos de los fármacos , Osteoblastos/fisiología , Células RAW 264.7 , Simvastatina/administración & dosificación , Ceras/síntesis química , Ceras/farmacologíaRESUMEN
BACKGROUND: The aim of the study was to develop an oral self-emulsifying drug delivery system (SEDDS) for exenatide and to evaluate its in vivo efficacy. METHODS: Exenatide was lipidised via hydrophobic ion pairing with sodium docusate (DOC) and incorporated in SEDDS consisting of 35% Cremophor EL, 25% Labrafil 1944, 30% Capmul-PG 8 and 10% propylene glycol. Exenatide/DOC was characterized in terms of lipophilicity evaluating the octanol/water phase distribution (logP). Exenatide/DOC SEDDS were characterized via droplet size analysis, drug release characteristics (log DSEDDS/release medium determination) and mucus permeation studies. Furthermore, the impact of orally administered exenatide/DOC SEDDS on blood glucose level was investigated in vivo on healthy male Sprague-Dawley rats. RESULTS: Hydrophobic ion pairing in a molar ratio of 1:4 (exenatide:DOC) increased the effective logP of exenatide from -1.1 to 2.1. SEDDS with a payload of 1% exenatide/DOC had a mean droplet size of 45.87⯱â¯2.9â¯nm and a Log DSEDDS/release medium of 1.9⯱â¯0.05. Permeation experiments revealed 2.7-fold improved mucus diffusion for exenatide/DOC SEDDS compared to exenatide in solution. Orally administered exenatide/DOC SEDDS showed a relative bioavailability (versus s.c.) of 14.62%⯱â¯3.07% and caused a significant (pâ¯<â¯.05) 20.6% decrease in AUC values of blood glucose levels. CONCLUSION: According to these results, hydrophobic ion pairing in combination with SEDDS represents a promising tool for oral peptide delivery.
Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Emulsionantes/metabolismo , Exenatida/metabolismo , Administración Oral , Animales , Células CACO-2 , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos/métodos , Emulsionantes/administración & dosificación , Exenatida/administración & dosificación , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/metabolismo , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
This study aimed to improve the mucus permeating properties of self-emulsifying drug delivery systems (SEDDS) by anchoring lipidized bromelain, papain and trypsin using palmitoyl chloride. SEDDS containing enzyme-palmitate conjugates were characterized regarding droplet size and zeta potential. Their mucus permeating properties were evaluated by Transwell diffusion and rotating tube method using fluorescein diacetate (FDA) as marker. Degree of substitution of modified enzymes was 35.3%, 47.8% and 38.5% for bromelain-palmitate, papain-palmitate and trypsin-palmitate, respectively. SEDDS as control and SEDDS containing enzyme-palmitate conjugates displayed a droplet size less than 50nm and 180-312nm as well as a zeta potential of -3 to -4 and -4 to -5mV, respectively. The highest percentage of permeation was achieved by introducing 5% papain-palmitate into SEDDS. It could enhance the mucus permeation of SEDDS in porcine intestinal mucus 4.6-fold and 2-fold as evaluated by Transwell diffusion and rotating tube method, respectively. It is concluded that mucus permeation of SEDDS can be strongly improved by incorporation of enzyme-palmitate conjugates.
Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Emulsionantes/administración & dosificación , Expectorantes/metabolismo , Moco/metabolismo , Animales , Bromelaínas/química , Bromelaínas/metabolismo , Emulsionantes/química , Emulsionantes/farmacocinética , Expectorantes/química , Mucosa Intestinal/metabolismo , Lípidos/química , Palmitatos/metabolismo , Papaína/química , Papaína/metabolismo , Tamaño de la Partícula , Permeabilidad , Porcinos , Tripsina/química , Tripsina/metabolismoRESUMEN
Energy is a major cost component in diets for poultry. We hypothesized that the supplementation of emulsifier blends in broiler diets may contribute to the efficient utilization of energy and in increasing fat digestibility, thereby improving performance. To test our hypothesis, an experiment was conducted to evaluate the effect of a blend of emulsifiers on growth performance, nutrient digestibility, serum lipid profiles, and meat quality of broilers. A total of 768 1-d-old Ross 308 male broiler chicks with an average initial body weight of 45.55 ± 0.34 g were used in a 35 days feeding trial. Broilers were sorted into 4 treatments, 12 replications per treatment, and 16 birds per pen. Dietary treatments consisted of corn-soybean meal based basal diet and the basal diet supplemented with 0.05%, 0.075%, and 0.10% emulsifier. As a result of this study, the inclusion of 0.05%, 0.075%, and 0.10% emulsifier blends (sodium stearoyl-2-lactylate (SSL) and Tween 20) in the basal diet linearly increased (P = 0.0001) body weight gain (BWG) and improved feed conversion ratio (FCR) (linear effect P = 0.0001) on d 7 to 21, d 21 to 35 as well as overall. Broilers fed with different levels of emulsifier blends also showed a linear increment (P < 0.05) in dry matter (DM) and fat digestibility. A trend of linear reduction (P = 0.051) in low density lipoprotein (LDL) in the serum of broilers fed emulsifier blend was observed. The lightness value of breast muscle color linearly increased (P = 0.001), the redness and yellowness values tended to increase (P = 0.072 and P = 0.094 respectively), and the water holding capacity (WHC) showed trends in reduction (P = 0.078) with an increase in the level of emulsifier blends. With regards to relative organ weight, spleen weight was linearly (P = 0.001) reduced with the increase in the supplemental levels of emulsifier blends. A positive correlation between emulsifier content in the diet and BWG, DM and fat digestibility, and breast muscle color indices, were also observed. In conclusion, emulsifier blend supplementation positively influenced growth performance and nutrient digestibility in broiler chickens.
Asunto(s)
Pollos/crecimiento & desarrollo , Emulsionantes/metabolismo , Lípidos/sangre , Carne/análisis , Polisorbatos/metabolismo , Estearatos/metabolismo , Alimentación Animal/análisis , Animales , Pollos/sangre , Pollos/fisiología , Dieta/veterinaria , Suplementos Dietéticos/análisis , Relación Dosis-Respuesta a Droga , Emulsionantes/administración & dosificación , Masculino , Polisorbatos/administración & dosificación , Distribución Aleatoria , Estearatos/administración & dosificaciónRESUMEN
This study aimed to compare the dissolution and the intestinal absorption of tacrolimus in self-microemulsifying drug delivery system (SMEDDS) and solid dispersion (SD). Poloxamer 188 SD was prepared by the combination of the solvent evaporation method and the freeze drying method. Hydroxypropyl methylcellulose (HPMC) SD was prepared by the solvent evaporation method combined with the vacuum drying method. The formation of SD was confirmed by SEM images which showed new solid phases. The SMEDDS was composed of oil (Labrafil M1944 CS 28%), surfactant (Cremophor EL 48%) and co-surfactant (Transcutol P 24%). The self microemulsion formed by the SMEDDS upon aqueous media had spherical droplets with a hydrodynamic size of 46.0±3.2nm. The dissolution of tacrolimus from SD and SMEDDS was performed in sink and non-sink conditions with various pH. As revealed by the DSC and FT-IR, the tacrolimus was molecularly or amorphously dispersed in the SMEDDS and SD. The in vivo intestinal absorption study in rats showed that both SMEDDS and SD improved the absorption of tacrolimus over the raw tacrolimus while the SMEDDS exhibited lower absorption rate constant (Ka) and apparent permeability coefficients (Papp) than the SD. The self-prepared SD with poloxamer 188 or HPMC had comparable intestinal absorption as compared with Prograf®. The tacrolimus-loaded SMEDDS and SD would be further compared by in vivo pharmacokinetic study.
Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Emulsionantes/administración & dosificación , Emulsionantes/síntesis química , Absorción Intestinal/efectos de los fármacos , Tacrolimus/administración & dosificación , Tacrolimus/síntesis química , Administración Oral , Animales , Química Farmacéutica/métodos , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/síntesis química , Portadores de Fármacos/metabolismo , Evaluación Preclínica de Medicamentos/métodos , Emulsionantes/metabolismo , Inmunosupresores/administración & dosificación , Inmunosupresores/síntesis química , Inmunosupresores/metabolismo , Absorción Intestinal/fisiología , Ratas , Tacrolimus/metabolismoRESUMEN
Saussurea lappa (SL) has been reported for its antioxidant and anti-ageing properties. Due to this reason it can be incorporated in a stable phytoformulations for cosmetic use. The objective of the study was to evaluate the anti-aging potential of cosmetic o/w emulsion containing the botanical extract of SL. An emulsion (o/w) was prepared using TEGO® Care 450 (Polyglceryl-3-Methyl Glucose Distearate) emulsifier and final emulsion was loaded with 4 % extract of SL in aqueous phase. This emulsion evaluated for its antioxidant and anti-ageing properties on healthy human subjects using a non-invasive technique called surface evaluation of living skin (SELS). The formulation containing SL extract showed significant (p<0.05) changes in Skin roughness (SEr) as -3.13%, -6.26%, -9.39%; Skin Scaliness (SEsc) as - 4.19%, -8.39%, -12.58%; Skin wrinkles (SEw) as -0.5%, -1.08%, -1.63%; and Skin smoothness (SEsm) as 3.28%, 6.57%, 9.85%, respectively, after 30, 60 and 90 days of continous use. Topical application of the cosmetic cream containing SL extract exerts have a significant anti-aging effects, perhaps due to the presence of Kaempferol, gallic acid, Caffeic acid and other essential phenolics.
Asunto(s)
Emulsionantes/administración & dosificación , Fitoquímicos/administración & dosificación , Extractos Vegetales/administración & dosificación , Saussurea/química , Envejecimiento de la Piel/efectos de los fármacos , Crema para la Piel/administración & dosificación , Piel/efectos de los fármacos , Estearatos/administración & dosificación , Administración Cutánea , Adulto , Emulsionantes/efectos adversos , Emulsiones , Humanos , Masculino , Pakistán , Fitoquímicos/efectos adversos , Extractos Vegetales/efectos adversos , Extractos Vegetales/aislamiento & purificación , Raíces de Plantas/química , Método Simple Ciego , Piel/patología , Crema para la Piel/efectos adversos , Estearatos/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Diarrhea often occurs during enteral nutrition. Recently, several reports showed that diarrhea improves by adding egg yolk lecithin, an emulsifier, in an enteral formula. Therefore, we evaluated if this combination could improve diarrhea outcomes. We retrospectively investigated the inhibitory effects on watery stools by replacing a polymeric fomula with that containing egg yolk lecithin. Then, we investigated the emulsion stability in vitro. Next, we examined the lipid absorption using different emulsifiers among bile duct-ligated rats and assessed whether egg yolk lecithin, medium-chain triglyceride, and dietary fiber can improve diarrhea outcomes in a rat model of short bowel syndrome. Stool consistency or frequency improved on the day after using the aforementioned combination in 13/14 patients. Average particle size of the egg yolk lecithin emulsifier did not change by adding artificial gastric juice, whereas that of soy lecithin and synthetic emulsifiers increased. Serum triglyceride concentrations were significantly higher in the egg yolk lecithin group compared with the soybean lecithin and synthetic emulsifier groups in bile duct-ligated rats. In rats with short bowels, the fecal consistency was a significant looser the dietary fiber (+) group than the egg yolk lecithin (+) groups from day 6 of test meal feedings. The fecal consistency was also a significant looser the egg yolk lecithin (-) group than the egg yolk lecithin (+) groups from day 4 of test meal feeding. The fecal consistency was no significant difference between the medium-chain triglycerides (-) and egg yolk lecithin (+) groups. Enteral formula emulsified with egg yolk lecithin promotes lipid absorption by preventing the destruction of emulsified substances by gastric acid. This enteral formula improved diarrhea and should reduce the burden on patients and healthcare workers.
Asunto(s)
Diarrea/etiología , Diarrea/prevención & control , Yema de Huevo , Emulsionantes/administración & dosificación , Nutrición Enteral/efectos adversos , Lecitinas/administración & dosificación , Anciano , Animales , Digestión , Modelos Animales de Enfermedad , Femenino , Ácido Gástrico , Humanos , Técnicas In Vitro , Masculino , Modelos Biológicos , Ratas Sprague-Dawley , Estudios Retrospectivos , Síndrome del Intestino Corto , Estómago/fisiología , Triglicéridos/sangreRESUMEN
ABSTRACT Two trials were aimed to evaluate beef tallow in diets with and without emulsifier on performance of pigs at growing-finishing phases. In the first trial, 15 barrows (22.03±0.62 kg) were distributed among three treatments: reference diet; test diet 1 (5% beef tallow) and test diet 2 (10% beef tallow). Beef tallow presented average value of 7130.97 kcal ME/kg. For the performance trail, 30 barrows (24.85±1.18 kg) were distributed among five treatments: T1 - diet with soybean oil and 3230 kcal ME /kg; T2 - diet with beef tallow and 3230 kcal ME/kg; T3 - diet with beef tallow and 3080 kcal ME/kg; T4 - diet with beef tallow, 3080 kcal/kg and 0.1% emulsifier; T5 - diet with beef tallow, 2930 kcal ME/kg and 0.1% emulsifier. Feed conversion was worse in animals fed diet with 3080 kcal ME/kg containing beef tallow and with 2930 kcal ME/kg with beef tallow and emulsifier. For economic availability, animals fed diet with beef tallow and 3230 kcal ME/kg and those fed diet with 3080 kcal ME/kg containing beef tallow and emulsifier, did not differ from animals fed diet with soybean oil, which enables the reduction up to 150 kcal ME/kg be compensated by emulsifier addition.