Development of a Solid Supersaturatable Self-Emulsifying Drug Delivery System of Docetaxel with Improved Dissolution and Bioavailability

Abstract

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...

Current Status of Supersaturable Self-Emulsifying Drug Delivery Systems

“…However, the hygroscopic natures of such solidification excipients should be taken into consideration during formulation design because they may result in particle agglomeration. Chen et al reported that the solid su-SEDDS prepared by spray drying with lactose provides an effective approach for improving the dissolution and BA of docetaxel with a low level of emulsifying excipients and provides a reference for good stabilization and the safety of SEDDSs [113].…”

Various Challenges and Opportunities in Oral Delivery of Anticancer Drugs

“…Example: a) Recently, solid supersaturate SEDDS of docetaxel via spray drying technique have been prepared and it was found to have about 8.77-fold and 1.45-fold higher oral bioavailability as compared to free drug and conventional SEDDS [46]. b) Self-emulsifying drug delivery system was developed of tamoxifen which showed about 3.8-fold and 9-fold enhancement in oral bioavailability as compared to clinically used tamoxifen citrate and tamoxifen free base, respectively [14].…”

“…It has been generally found that the drug release is often retarded due to high lipophilic nature of the overall system, but considering the urge to increase the drug release rate; polymer lipid hybrid nanoparticles were developed. These are based on the same principle of SLNs, and incorporation of the ionic polymers helps in improving the encapsulation of water-soluble ionic drugs such as doxorubicin hydrochloride [46].…”

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“…in salicylic acid and docetaxel 8,44 SEDDS formulation, HPMC is used as precipitation inhibitor. A fivefold increase in bioavailability has been observed with PNU-91325 when HPMC in place of propylene glycol, is used as precipitation inhibitor 45 .…”