Analysis Of 7’-Epi-Docetaxel In DTX-loaded Albumin Nanoparticles Using A Freeze-Drying Approach

Since freeze-drying protein drugs maintain their biological activities and will have their original properties after being rehydrated,the freeze-drying method is widely applicable in the field of protein drugs.Thus the freeze-drying method can contribute to reserving the protein drugs for a long period because of the loss of water in the sublimation stage.But for some specific protein drugs,we have to select proper relevant parameters to obtain the optimal freeze drying curve during the freeze-drying process.Meanwhile,we usually add the lyoprotectants to maintain the stability of the protein drugs in the samples generated by the free-drying method.Docetaxel(DTX),an analogue of Paclitaxel,can suppress the growth of cancer cells through the inhibition of microtubule depolymerization.At present,Docetaxel Injection and Docefrez Lyoph are the main dosage forms acquired the approval for marketing from the FDA.Because of the strong poor aqueous solubility,Docetaxel uses the surfactant polysorbate80 and ethyl alcohol as the intermediary,which has been reported in the contribution to acute hypersensitivity reactions and peripheral neuropathy.As a new dosage form,DTX-loaded albumin nanoparticles have been successfully fabricated by the American BioScience Company.The breast cancer treatment stages of clinical phase I and first-line prostate cancer treatment stages of clinical phase II have been completed.As the main related substance of Docetaxel,the 7’-Epi-Docetaxel has not been reported its toxicity of pharmacology by relevant papers and the United States pharmacopoeia sets an upper bound of 2%for it in the samples of Docetaxel Injection and Docefrez Lyoph.In order to constrain the generation of 7’-Epi-Docetaxel which is the main related substance in DTX-loaded Albumin Nanoparticles,this paper conducts four experiments as the following:Firstly,we research the relationship between the increase of 7’-Epi-Docetaxel and the residual solvents called ethyl alcohol via the stability testing of DTX-loaded Albumin Nanoparticles;Secondly,we filter the parameters during the freeze-drying process and we choose proper parameters to obtain the optimal freeze drying curve based on the rehydrated condition and the amount of ethyl alcohol;Thirdly,we analyze the relationship between the residual water after the free-drying process and 7’-Epi-Docetaxel;Lastly,we select the DTX-loaded Albumin Nanoparticles lyoprotectants and obtain the best lyoprotectants that can constrain the increase of the 7’-Epi-Docetaxel.By these four experiments,we can conclude that as the main relevant substance in DTX-loaded Albumin Nanoparticles,the 7’-Epi-Docetaxel can constrain by decreasing the amount of residual solvents called ethyl alcohol and adding the best lyoprotectants during the freeze-drying process.At the same time,we can conclude the increased amount of 7’-Epi-Docetaxel is irrelevant to the residual water in the samples.