Self-emulsifying drug delivery systems (SEDDS) are defined as isotropic mixtures of oils, surfactants, and co-solvents. The systems can form fine oil in water (o/w) emulsions (SEDDS) with a droplet size between 100 and 1000 nm or in microemulsions (SMEDDS) with a droplet size of less than 100 nm when meeting with aqueous media. SEDDS/ SMEDDSs may offer a new strategy for enhancing the oral bioavailability of poorly water soluble and lipophilic drugs. [1][2][3][4] However, recent studies suggest that there are some shortcomings in the stability and safety of SEDDS/ SMEDDSs. First of all, SEDDS/SMEDDSs are normally in liquid or semi-solid form and are encapsulated in soft gelatin capsules with high manufacturing costs. 5) Some of the alcohol or other cosolvents in the SEDDSs possibly move into the shells of the capsule, which results in the precipitation of the drug.1,6) Therefore, a new SEDDS called the solid selfemulsifying drug delivery system (S-SEDDS) was prepared by incorporating a liquid self-emulsifying formulation into a solid dosage form.5-8) S-SEDDSs have the advantages of higher stability, longer storage time, lower irritation of gastrointestinal tract and lower production costs compared with conventional SEDDS. Secondly, plenty of surfactants and cosolvents are added into the formulations of SEDDS/SMEDDSs to prevent precipitation of the drug when diluted by gastrointestinal (GI) fluids. However, more surfactants may cause gastrointestinal side effects 9,10) ; therefore, a new thermodynamically stable formulation called the supersaturatable self-emulsifying drug delivery system (sSEDDS) was designed to contain a reduced amount of surfactant and watersoluble polymers as a supersaturated promoter to prevent precipitation of the drug by generating and maintaining a supersaturated state in vivo. In comparison with conventional SEDDSs, sSEDDS formulations can result in enhanced stability and lower side effects. 10)This study combines the advantages of S-SEDDSs with those of sSEDDSs by incorporating a supersaturatable liquid self-emulsifying formulation into a solid dosage form. This can possibly overcome the disadvantages of liquid SEDDSs and the high surfactant levels in conventional SEDDS formulations described above. Although increasing studies have focused on the area of S-SEDDSs or sSEDDSs, related reports are limited. There has been no previous work that was carried out to investigate the combination of SEDDS and S-SEDDS technology with sSEDDSs. Docetaxel (DTX) is an antineoplastic agent belonging to the second generation of the taxoid family. It was identified in 1986 as an alternative to paclitaxel. It has become one of the most important chemotherapeutic agents and is widely used against ovarian carcinoma, advanced breast cancer, lung cancer, and head/neck cancer.11-13) Docetaxel is practically insoluble in water and is often dissolved in polysorbate 80 (Tween 80). However, due to the high content of Tween 80, acute hypersensitivity reactions have been found in the majority of patients treated in t...

An emulsified solid dispersion of docetaxel was prepared and characterized in vitro. In contrast to conventional solid dispersions, emulsifying pharmaceutical excipients and hydroxypropyl methylcellulose (HPMC) as a supersaturation promoter were introduced into the PEG6000-based solid dispersion to further improve its solubilizing capability. The solubility, dissolution in vitro and stability of the prepared emulsified solid dispersions were studied taking into consideration of the effects of different emulsifying excipients, preparation methods and the media. Results of the emulsified solid dispersion of docetaxel showed that the solubility and dissolution at 2 h were 34.2- and 12.7-fold higher than the crude powder. The type of emulsifying excipient used had a significant influence on the dissolution of the emulsified solid dispersion. The dissolution of the emulsified solid dispersion prepared by the solvent-melting method or the solvent method was higher than the melting method. There were no apparent differences among the dissolution media utilized. The status of the drug in the emulsified solid dispersion was observed in an amorphous or a molecular dispersion state by differential thermal analysis and powder Xray diffraction. In conclusion, the incorporation of emulsifying pharmaceutical excipients and HPMC with polymers into a solid dispersion could be a new and useful tool to greatly increase the solubility and dissolution of poorly water-soluble drugs.

Topiramate (TPM) was an antiepileptic agent commonly used in clinical. Studies showed that an oral preparation of TPM with extended-release manner could bring some benefits for epileptics. In this paper, controlled release push-pull osmotic pump (PPOP) tablets of sparingly water-soluble TPM were successfully prepared. This bi-layer tablet core mainly consisted of sodium chloride as osmotic promoting agent and polyethylene oxide as suspending and pushing agents. The influences of osmotic agents, pushing agents and the compositions of coating membrane on TPM release profiles were evaluated. An optimal formulation of TPM-PPOP was obtained through single-factor experiments. In vitro release tests showed that the optimum formulation could release TPM at an approximate zero-order rate up to 8 h. Pharmacokinetic behaviors of TPM-PPOP tablets were evaluated and compared with the immediate release capsules after an oral single dose in beagle dogs. Pharmacokinetics results demonstrated that the TPM-PPOP tablet was able to provide a prolonged release of TPM with longer tmax and mean residence time. Lower fluctuations of drug plasma levels could also be achieved with TPM-PPOP tablets. These results suggested that sparely water-soluble drugs as TPM can be designed to PPOP for efficacy and safety use.