Formulation optimization for high drug loading colonic drug delivery carrier

High drug loading (DL) carrier is an effective way to cure the cancerous cells. High drug loading is also one of the key issues in the drug delivery research, especially the colonic drug delivery system by oral administration. The times of drug intake could be remarkably reduced if high drug loading carriers are administered. At the same time, the related formulation materials could be effectively utilized. One major obstacle with the preparation of this system is the difficulty to encapsulate the hydrophilic drug into hydrophobic encapsulation polymer. A design of high drug loading delivery system with biodegradable, biocompatible materials and optimization of the fabrication process is a potential solution to solve the problem. So in this research, 5-Fluorouracil (5-FU) loaded Poly (lactide-co-glycolide) (PLGA) nanoparticles were prepared by double emulsion and solvent evaporation method. Several fabrication parameters including theoretical drug loading, volume ratio of outer water phase to the first emulsion, pH value of outer aqueous phase and emulsifier PVA concentration were optimized to get a high drug loading nanoparticles. The result shows that with the increase of theoretical drug loading, the actual drug loading increased gradually. When adjusted the pH value of outer aqueous phase to the isoelectric point (8.02) of 5-Fluorouracil, the drug loading exhibited a higher one compared to other pH value solution. Relative higher volume ratio of outer water phase to the first emulsion was also beneficial for the enhancement of drug loading. But the nanoparticles size increased simultaneously due to the lower shearing force. When increased the PVA concentration, the drug loading showed an increase first and following a drop.

Microchannel emulsification study on formulation and stability characterization of monodisperse oil-in-water emulsions encapsulating quercetin

The study used microchannel emulsification (MCE) to encapsulate quercetin in food grade oil-in-water (O/W) emulsions. A silicon microchannel plate (Model WMS 1-2) comprised of 10,300 discrete 10 × 104 μm microslots was connected to a circular microhole with an inner diameter of 10 μm. 1% (w/w) Tween 20 was used as optimized emulsifier in Milli-Q water, while 0.4 mg ml-1 quercetin in different oils served as a dispersed phase. The MCE was carried by injecting the dispersed phase at 2 ml h-1. Successful emulsification was conducted below the critical dispersed phase flux, with a Sauter mean diameter of 29 μm and relative span factor below 0.25. The O/W emulsions remained stable in terms of droplet coalescence at 4 and 25 °C for 30 days. The encapsulation efficiency of quercetin in the O/W emulsions was 80% at 4 °C and 70% at 25 °C during the evaluated storage period.

Preparation of monodisperse aqueous microspheres containing high concentration of L-ascorbic acid by microchannel emulsification

Monodisperse aqueous microspheres containing high concentrations of l-ascorbic acid with different concentrations of sodium alginate (Na-ALG) and magnesium sulfate (MgSO4) were prepared by using microchannel emulsification (MCE). The continuous phase was water-saturated decane containing a 5% (w/w) hydrophobic emulsifier. The flow rate of the continuous phase was maintained at 10 mL h(-1), whereas the pressure applied to the disperse phase was varied between 3 and 25 kPa. The disperse phase optimized for successfully generating aqueous microspheres included 2% (w/w) Na-ALG and 1% (w/w) MgSO4. At a higher MgSO4 concentration, the generated microspheres resulted in coalescence and subsequent bursting. At a lower MgSO4 concentration, unstable and polydisperse microspheres were obtained. The aqueous microspheres generated from the MCs under optimized conditions had a mean particle diameter (dav) of 14-16 µm and a coefficient of variation (CV) of less than 8% at the disperse phase pressures of 5-15 kPa.

Formulation of monodisperse water-in-oil emulsions encapsulating calcium ascorbate and ascorbic acid 2-glucoside by microchannel emulsification

The aim of this study was to investigate the effects of the emulsifying conditions and emulsifier type on production of water-in-oil (W/O) emulsions encapsulating ascorbic acid derivatives by microchannel (MC) emulsification. The ascorbic acid derivatives added in a dispersed aqueous phase are calcium ascorbate (AA-Ca) and ascorbic acid 2-glucoside (AA-2G). The continuous phase used was decane, soybean oil or their mixture, containing 5% (w/w) tetraglycerin monolaurate condensed ricinoleic acid ester or sorbitan trioleate. A hydrophobized silicon MC array plate (model: MS407) with a channel depth of 7μm was used for MC emulsification. The use of MC emulsification enabled successful encapsulation of AA-Ca and AA-2G in monodisperse W/O emulsion droplets with coefficients of variation (CV) less than 7%. Their average droplet diameter (dav) increased with increasing the continuous-phase viscosity that is similar or higher than the dispersed-phase viscosity. The dav and CV of the resultant monodisperse W/O emulsions were unaffected by the dispersed-phase flow rate below critical values of 1.2-1.6mLh-1 when using decane as the continuous-phase medium.

Monodisperse W/O/W emulsions encapsulating L-ascorbic acid: Insights on their formulation using microchannel emulsification and stability studies

Stabilizing l-ascorbic acid is a challenge for food industries. The present study aimed to formulate monodisperse food-grade water-in-oil-in-water (W/O/W) emulsions containing a high concentration of l-ascorbic acid in an inner aqueous phase using homogenization and subsequent microchannel emulsification (MCE). The microchannel (MC) array plate used here was a silicon asymmetric straight-through MC array that consists of numerous 10. μm. ×. 100. μm microslots with a 30. μm depth, each connected to a 10. μm-diameter circular MC with a 70. μm depth. Water-in-oil (W/O) emulsions contained a soybean oil solution with 4-8% (w/w) tetraglycerin condensed ricinoleic acid ester as a continuous phase and an aqueous solution with 10-30% (w/v) l-ascorbic acid, 1% (w/w) magnesium sulfate, and 1% (w/v) gelatin as an inner aqueous phase. The W/O emulsion droplets formulated using a rotor-starter homogenizer had average droplet diameters of 2.6-2.9. μm and coefficients of variation (CVs) of 13-17%. MCE was performed using a dispersed W/O emulsion phase and a 5. mM phosphate buffer containing 1% (w/w) decaglycerol monolaurate and 10-30% (w/v) D(+)-glucose as an outer aqueous phase. Monodisperse W/O/W emulsions containing W/O droplets with average diameters of 26.0-31.5. μm and CVs below 10% were successfully formulated via an asymmetric straight-through MC array at a low hydrophobic emulsifier concentration, regardless of l-ascorbic acid concentration. The W/O droplets dispersed in these monodisperse W/O/W emulsions were physically stable in variation of average diameter and CV for more than 10d of storage at 4. °C. The monodisperse W/O/W emulsions also exhibited l-ascorbic acid retention exceeding 80% during storage.

Preparation and characterization of water-in-oil-in-water emulsions containing a high concentration of L-ascorbic acid

This study sought to encapsulate a high concentration of L-ascorbic acid, up to 30% (w/v), in the inner aqueous phase of water-in-oil-water (W/O/W) emulsions with soybean oil as the oil phase. Two-step homogenization was conducted to prepare W/O/W emulsions stabilized by a hydrophobic emulsifier and 30% (v/v) of W/O droplets stabilized by a hydrophilic emulsifier. First-step homogenization prepared W/O emulsions with an average aqueous droplet diameter of 2.0 to 3.0 μm. Second-step homogenization prepared W/O/W emulsions with an average W/O droplet diameter of 14 to 18 μm and coefficients of variation (CVs) of 18% to 25%. The results indicated that stable W/O/W emulsions containing a high concentration of L-ascorbic acid were obtained by adding gelatin and magnesium sulfate in the inner aqueous phase and glucose in both aqueous phases. L-Ascorbic acid retention in the W/O/W emulsions was 40% on day 30 and followed first-order kinetics.

Preparation and characterization of water-in-oil emulsions loaded with high concentration of l-ascorbic acid

The present study was conducted to encapsulate higher concentration of l-ascorbic acid up to (30 g 100 mL-1) in the dispersed phase of water-in-oil (W/O) emulsions. Their continuous phase contained refined soybean oil or Moringa oleifera oil and a food-grade hydrophobic emulsifier. The volume fraction of the dispersed phase was fixed as to 30%. W/O emulsions with l-ascorbic acid retention greater than 95% were prepared using rotor-stator homogenizer at 7000 rpm for 5 min. The prepared W/O emulsions under this operating conditions had average droplet diameter of 2.0-3.0 μm and coefficients of variation of 13%-22%. All the W/O emulsions were stable for more than 30 days at 4 °C or 25 °C with slight increase in average droplet diameter and without phase separation. Their l-ascorbic acid retentions were 50 g 100 g-1 at 4 °C and 30 g 100 g-1 at 25 °C after 30 days of storage. l-ascorbic acid retention ratio of the prepared W/O emulsions followed first-order kinetics with a good fit.