Self-emulsifying Formulation Research Articles

Controlled release of a self-emulsifying formulation from a tablet dosage form: Stability assessment and optimization of some processing parameters

The objective of this study was to evaluate the effect of some processing parameters on the release of lipid formulation from a tablet dosage form. A 17-run, face-centered cubic design was employed to evaluate the effect of colloidal silicates ( X 1), magnesium stearate mixing time ( X 2), and compression force ( X 3) on flow, hardness, and dissolution of Coenzyme Q 10 (CoQ 10) lipid formulation from a tablet dosage form. The optimized formulation was subsequently subjected to a short-term accelerated stability study. All preparations had a flowability index values ranging from 77 to 90. The cumulative percent of CoQ 10 released within 8 h ( Y 5) ranged from 40.6% to 90% and was expressed by the following polynomial equation: Y 5 = 49.78 − 16.36 X 1 + 2.90 X 2 − 3.11 X 3 − 0.37 X 1 X 2 + 1.06 X 1 X 3 − 1.02 X 2 X 3 + 11.98 X 1 2 + 10.63 X 2 2 − 7.10 X 3 2 . When stored at 4 °C, dissolution rates were retained for up to 3 months. Storage at higher temperatures, however, accelerated lipid release and caused leakage, and loss of hardness. Processing parameters have a profound effect on the release of lipid formulations from their solid carriers. While optimized controlled release formulations could be attained, further considerations should be made to prepare “liquisolids” that are physically stable at higher storage temperatures.

Study of the preparation of sustained-release microspheres containing zedoary turmeric oil by the emulsion–solvent-diffusion method and evaluation of the self-emulsification and bioavailability of the oil

The purpose of this study was to design a sustained-release formulation of an oily drug. The sustained-release microspheres with self-emulsifying capability containing zedoary turmeric oil (ZTO) were prepared by the quasi-emulsion–solvent-diffusion method. The micromeritic properties, the efficiency of emulsification and the drug-release behavior of the resultant microspheres were investigated. The bioavailability of the microspheres was compared with conventional ZTO self-emulsifying formulations for oral administration using 12 healthy rabbits. An HPLC method was employed to determine the concentration of germacrone in plasma, which was used as an index of ZTO. Spherical and compacted microspheres with average diameters of 100–600 μm have been prepared, and their release behavior in distilled water containing 1.2% (w/v) of polysorbate-80 can be controlled by the ratio of polymer/Areosil200 in the microspheres. The resultant emulsions with mean droplet sizes of 200–500 nm are produced when the microspheres are immersed in phosphate buffer (pH 6.8) under gentle agitation. The stability and the droplet size of the resultant emulsions are also affected by the polymer/Areosil200 ratio in the formulation, while the amount of talc has a marked effect on the self-emulsifying rate. The plasma concentration–time profiles with improved sustained-release characteristics were achieved after oral administration of the microspheres with a bioavailability of 135.6% with respect to the conventional self-emulsifying formulation (a good strategy for improving the bioavailability of an oily drug). In conclusion, the sustained-release microspheres with self-emulsifying capability containing ZTO have an improved oral bioavailability. Our study offers an alternative method for designing sustained-release preparations of oily drugs.

A new self-emulsifying formulation of itraconazole with improved dissolution and oral absorption

To enhance the dissolution and oral absorption of poorly water-soluble itraconazole, self-emulsifying drug delivery system (SEDDS) composed of oil, surfactant and cosurfactant for oral administration of itraconazole was formulated, and its physicochemical properties and pharmacokinetic parameters of itraconazole were evaluated. Among the surfactants and oils studied, Transcutol®, Pluronic® L64 and tocopherol acetate were chosen that showed the maximal solubility to itraconazole. The solubility of itraconazole was further improved by the addition of hydrochloric acid. Droplet size of itraconazole emulsion was kept constant both in simulated gastric fluid without pepsin (pH 1.2) and simulated intestinal fluid (pH 6.8) throughout 120-min incubation period. Itraconazole in the SEDDS rapidly dissolved in every dissolution medium whereas the Sporanox® showed different dissolution patterns during the 120-min incubation according to the dissolution media. In fasted and fed normal diet group, AUC0→24 h and the mean maximum plasma level (Cmax) of itraconazole after oral administration of SEDDS in rats were comparable to those of itraconazole after oral dose of Sporanox®. However, in fed lipidic diet group, AUC and Cmax after oral administration of SEDDS in rats were 3.7- and 2.8-fold higher, respectively, compared with those of Sporanox®. These results demonstrate that the SEDDS of itraconazole composed of Transcutol®, Pluronic® L64 and tocopherol acetate greatly enhanced the bioavailability of itraconazole after the dose, particularly not influenced by food intake or not. Thus, this system may provide a useful dosage form for oral water-insoluble drug without food effect.

Bioavailability assessment of ketoprofen incorporated in gelled self-emulsifying formulation: A technical note

Based on the results of the present study, it is apparent that the gelled SEF containing KPF did not significantly alter its bioavailability as compared with that of an immediate release solid dosage form when administered to human volunteers by the oral route.

A novel formulation design about water-insoluble oily drug: preparation of zedoary turmeric oil microspheres with self-emulsifying ability and evaluation in rabbits

To enhance in vivo absorption of zedoary turmeric oil (ZTO) and develop new formulations of a water-insoluble oily drug, novel ZTO microspheres with self-emulsifying ability, called self-emulsifying microspheres here, were prepared in a liquid system by the quasi-emulsion solvent diffusion method. The microspheres containing hydroxypropyl methylcellulose acetate succinate (HPMCAS-LG), Talc and Aerosil 200 formed the stable surfactant-free emulsion when exposed to the pH 6.8 phosphate buffer, and were significantly different from the conventional self-emulsifying systems (SES), defined as isotropic mixtures of oil, surfactant and drug. Micromeritic properties, the efficiency of emulsification and the drug-release rate of the resultant microspheres were investigated. The bioavailability of the microspheres to the conventional self-emulsifying formulation for oral administration was evaluated in 12 healthy rabbits. A HPLC method was employed to determine the plasma concentration of Germacrone, an indexical component found in ZTO. The release rates of ZTO and Germacrone from the microspheres were enhanced significantly with increasing amounts of dispersing agents, and the efficiency of self-emulsification greatly depended on the HPMCAS-LG/Aerosil 200 ratio. The emulsion droplets released from the microspheres were much smaller than that of the conventional SES. The microsphere bioavailability ( F) to the conventional SES for oral administration was 157.7%. Our method greatly improved the bioavailability of the water-insoluble oily drug from the self-emulsifying microspheres over the conventional SES and it is useful for the oily drug to form solid preparations.

Influence of cryogenic grinding on properties of a self-emulsifying formulation

Recently, self-emulsifying drug delivery systems (SEDDS) have been developed as a method to deliver lipophilic drugs. Gelucire® 44/14 is an excipient, from the lauroyl macrogolglycerides family, producing a fine oil-in-water emulsion when introduced into an aqueous phase under gentle agitation as SEDDS, improving thereby solubility of poorly water-soluble drugs and their bioavailability. The aims of this study were to process Gelucire® 44/14 into a powder by cryogenic grinding to produce solid oral dosage forms and to investigate influence of this process on different properties of a formulation made of Gelucire® 44/14 and ketoprofen (90/10). Cryogenic grinding produced Gelucire® 44/14 in a powder form and this process did not change its physical properties, emulsification capacities and dissolution performances of the formulation tested. However, interactions took place between ketoprofen and Gelucire® 44/14 with a decrease of the melting peak and a reduction of the droplet size of the formed emulsion. The influence of drug–Gelucire® 44/14 interactions must be investigated case by case in any formulations.

Influence of cryogenic grinding on properties of a self-emulsifying formulation

Recently, self-emulsifying drug delivery systems (SEDDS) have been developed as a method to deliver lipophilic drugs. Gelucire ® 44/14 is an excipient, from the lauroyl macrogolglycerides family, producing a fine oil-in-water emulsion when introduced into an aqueous phase under gentle agitation as SEDDS, improving thereby solubility of poorly water-soluble drugs and their bioavailability. The aims of this study were to process Gelucire ® 44/14 into a powder by cryogenic grinding to produce solid oral dosage forms and to investigate influence of this process on different properties of a formulation made of Gelucire ® 44/14 and ketoprofen (90/10). Cryogenic grinding produced Gelucire ® 44/14 in a powder form and this process did not change its physical properties, emulsification capacities and dissolution performances of the formulation tested. However, interactions took place between ketoprofen and Gelucire ® 44/14 with a decrease of the melting peak and a reduction of the droplet size of the formed emulsion. The influence of drug–Gelucire ® 44/14 interactions must be investigated case by case in any formulations.

Comparative bioavailability of L-683,453, a 5α-reductase inhibitor, from a self-emulsifying drug delivery system in Beagle dogs

Bioavailabilities (BA) of the lipophilic compound, L-683,453, from several formulations were determined in fasted and fed purpose-bred Beagle dogs following oral administration and an i.v. reference dose. The compound is poorly soluble in water (∼0.001 mg/mL) and exhibited very low BA, 0.2%, from suspensions in methyl cellulose, in fasted dogs. Addition of sodium dodecyl sulfate (SDS) into suspensions increased BA significantly to 0.6% in fasted ( P = 0.05) and to 1.7% in fed animals ( P < 0.01). A more dramatic enhancement in BA, up to 13.7%, was achieved from a self-emulsifying formulation composed of mono- and di-glycerides of caprylic/capric acids (MDG) and surfactants. It was found that tolerability and efficacy of MDG-based formulations at 16 mg/kg depend not only on the dose but also on the dosing volume. A volume of 2 mL/kg caused emesis, while a volume of 1 mL/kg was well tolerated. In contrast to its effect on suspensions, food had no statistically significant effect on BA of self-emulsifying formulations at dosing volumes of 1 mL/kg and 0.25 mL/kg. However, peak plasma concentrations were achieved faster in fed than in fasted animals.