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Goserelin is a peptide drug that suppresses levels of testosterone and oestradiol [1]. The current formulation is presented in a sustained-release depot with several approved indications such as treatment of endometriosis, prostate cancer and breast cancer. The depots are placed subcutaneously with a large bore needle, hence there is a need for less invasive administration. An oral formulation in a drug delivery system such as Pheroid® would offer ease of administration to the patient, improved bioavailability as well as reduced manufacturing costs [2]. Therefore, the aim of this study was to determine the effect of entrapment of goserelin in Pheroid® on the pharmacokinetics (PK) of goserelin as well as the pharmacodynamic (PD) effects, in mice. Goserelin was entrapped in Pheroid® and characte- rized in terms of size, zeta potential and morphology. Male Balb/c mice, 6–8 weeks old were administered goserelin subcutaneously and goserelin entrapped in Pheroid® orally. At selected time points, mice were euthanised, blood collected and analysed for goserelin and testosterone levels by LCMS/MS to determine the PK and PD effects respectively. The size and zeta potential of Pheroid® remained in the expected ranges suggesting that entrapment of goserelin had no effect on Pheroid® vesicle size and stability. Confocal imaging showed satisfactory quality of the Pheroid® and goserelin did not have any effect on the Pheroid® structure. Entrapment of goserelin in Pheroid led to detectable levels of goserelin in plasma of the mice and a corresponding decrease in testosterone levels. The results suggest that Pheroid® may improve the oral bioavailability of goserelin and could be a potential strategy for an oral formulation which would be less invasive for patients

Goserelin is a type of hormone therapy used in addition to standard adjuvant therapy. Currently, goserelin is only available as a slow releasing subcutaneous implant but this is an invasive and generally not well- tolerated method of administration. By using a drug delivery system (DDS), peptides can be protected from the harsh environment of the gastrointestinal (GI) tract. Pheroid® technology is one such example of a drug delivery system. This delivery system is a patented, colloidal drug delivery system and is capable of targeting specific areas for treatment, transportation of genetic material to the cellular nucleus and the decrease of drug resistance, all this while improving the delivery of dynamic complexes [1,2]. The prospect of changing to a less invasive administration method will yield a great advantage. Goserelin was investigated in female Balb/c mice. Pheroid® technology was used as a drug delivery system (DDS) to compare the bioavailability of goserelin subcutaneous depot against a peroral formulation with goserelin pro-Pheroid® formulation. The mice were divided into three groups; group one received goserelin subcutaneously, group 2 received an oral dose of 4 mg/kg pro-Pheroid®-goserelin and group 3 being the control group which received only pro- Pheroid®. Vaginal cytology was evaluated to track the disruption of the oestrus cycle Vaginal cytology results indicated a disruption in the oestrus cycle in the subcutaneous groups and the pro- Pheroid®-goserelin oral group. No disruption in the cycle was observed for the pro-Pheroid® oral group. Entrapment in Pheroid® resulted in oral bioavailability of goserelin as indicated by the related effect on the oestrus cycle. No disruption of the cycle was observed in the pro-pheroid® oral group, thus, goserelin was successfully absorbed in the blood after the peroral administration with pro-Pheroid. In conclusion, Pheroid® technology seemed to protect goserelin from the harsh environment of the gastrointestinal tract and could thus be a helpful DDS

The purpose of this reported study was to develop and validate an LC-MS/MS method for the quantification of goserelin in a Pheroid (R) formulation simulated intestinal fluid. Biopharmaceuticals are formulated in drug delivery systems to improve their gastrointestinal stability. Goserelin, a peptide drug was formulated in Pheroid (R) delivery system and its gastrointestinal stability assessed using simulated intestinal fluid, which required an assay to determine the varying amounts of goserelin remaining after a specific time. Several extraction methods and solvents investigated to extract goserelin from complex matrix led to either poor recovery, peak shape or high background interference. A rapid gradient reversed-phase method coupled to tandem mass spectrometry detection was optimized for the separation and quantification of the extracted peptide. A simple, reproducible and good recovery extraction procedure for goserelin quantification was achieved through simultaneous acetonitrile protein precipitation and water-saturated n-butanol liquid-liquid extraction with water dilution. The method was found to be rapid, specific, precise and accurate, and successfully applied to determine goserelin remaining content in a simulated intestinal fluid, with potential use in other lipid-based formulation evaluated in simulated intestinal fluids. (C) 2019 Elsevier B.V. All rights reserved