The Development Of Tamoxifen Gel Plaster

In recent years,the prevalence of breast cancer has been increasing.Breast cancer has become one of the major malignant tumors that are harmful to women's physical and mental health.The current clinical treatment includes surgery,radiotherapy,chemotherapy,endocrine therapy,interventional therapy and so on.Among those treatment,endocrine therapy plays an important role in the treatment of advanced breast cancer.Tamoxifen is the first generation of selective estrogen receptor modulators,showing estrogenic and antiestrogenic activities through combination with estrogen receptor.It is the first-line endocrine drug which is the most effective and the longest time treating estrogendependent advanced breast cancer.As one of the preferred drugs which is used of postoperative endocrine adjuvant treatment,Tamoxifen apply to estrogen receptor and progesterone receptorpositive postmenopausal women patients with breast cancer.At present,the main route of administration of tamoxifen is oral,mainly for tablets,granules,capsules..Tamoxifen is almost insoluble in water,so the above oral forms have bad dissolutions in gastrointestinaltract.It leads to low bioavailability and drug first pass effect,large oral blood concentration fluctuations.Long-term use it can lead to venous thrombosis and increase the risk of endometrial cancer.In order to reduce the side effects of tamoxifen and increase the clinical efficacy,it is considered that the administration method is changed from oral to transdermal drug delivery.The transdermal preparation can avoid the first pass effect of oral administration,the fluctuation of blood drug concentration,and reduce drug toxicity,adverse effect,the number of administration,and is convenient to delivery.Gel plaster(formerly Babu paste or gel paste)refers to raw material drug and appropriate hydrophilic matrix emplastrum which after blending evenly coated on the backing material made of plaster,beingthe representative of skin preparation.The gel plaster has good biocompatibility,no sensitization and irritation,convenient use,no pollution to clothes,can be repeatedly exposed,drug-polymer interactions,transdermal absorption,low production cost,etc.In particular,the application of gel patch in the breast part,drugs can constantly by percutaneous diffusion,osmosis,direct access to breast cancer lesion in the breast tissue.It can increase tamoxifen concentration significantly,and improve the therapeutic effect of breast cancer.This topic selects tamoxifen as a model drug,preparing tamoxifen gel plaster.This paper established a method of the determination of tamoxifen in vitro study of tamoxifen gel in vitro skin plaster permeability,the preparation process and the prescription of tamoxifen gel plaster.The main study about the article can be summarized as follows:1 Establishment of a method for the determination of tamoxifen in vitroObjective: To establish a method for the determination of tamoxifen in vitro.Methods: PLATISILTM ODS column(150 x 4.6 mm,5 m);the mobile phase was methanol: 1%(three triethylamine acetic acid to adjust p H to 8.5)for 89:11(V/V);the volume flow rate of 1 m L /min;the detection wavelength of 238 nm;column temperature of 25 DEG C;the injection volume was 10 m L.Results: the peak area and mass concentration of tamoxifen standard solution to do linear regression,the regression equation is:C=0.0531 A-0.0048(r=0.9998),tamoxifen good relationship in 0.081~ 2.424 ? g · ml-1range and peak area of linear.The average recovery rate of low,medium and high concentrations was 99.6%,RSD was 0.98%.The same sample solution was determined at 0,2,4,8,12,24 h,respectively,and the peak area of RSD was about1.06%.Conclusion: the chromatographic conditions for HPLC determination,and the precision,recovery,specificity and a series of experimental methodology,the method is accurate,feasible,conform to the Chinese Pharmacopoeia,can be used for detection of tamoxifen in vitro.2 Study on permeability of tamoxifen in vitro pig skin gel plasterObjective: To study the permeability test method of gel plaster pigskin tamoxifen in vitro.Methods: using the modified Franz diffusion cell and excised porcine ear skin in vitro transdermal test on tamoxifen permeation rate and screening indexes of infiltration and multiple effects of Azone,oleic acid,propylene glycol,lauryl alcohol enhancers and its associated with in vitro effects of enhancers on transdermal permeation.Results:different penetration enhancers has the function of promoting transdermal enhancers,one with 2% azone transdermal effect best,its penetration rate increased 14.69 times compared with the control group,the joint enhancers in propylene glycol(20%)azone+(2%)penetration ability is the strongest,compared with the control group increased 18.65 times.Conclusion: propylene glycol(20%)and(2%)the combined use of Azone as the penetration enhancer for tamoxifen gel plaster.3 Study on tamoxifenObjective: To investigate the physical and chemical properties of tamoxifen and lay the theoretical foundation for the optimization of the prescription.Methods: Based on the solubility in different solvents on the determination of tamoxifen,preferably solubilizer and determine the optimal proportion;determine the proportion of optimal ratio of glycerol and water and aqueous and compatibilization system.Results: the preliminary determination of Twain-80: according to the leaf oil2:1 as the solubilization system,and determine the ratio of water and glycerol to 2:1,water system and the ratio of solvent to 20:1.Conclusion: the proportion of compatibility,the ratio of oil to water,the ratio of water phase to the capacity of expansion were determined before the study,which laid a theoretical foundation for the further optimization of prescription.4 The development of tamoxifen gel plasterObjective: to optimize the prescription of tamoxifen gel plaster.Methods: adopt the method of optimization of single factors and central composite design and response surface,with initial viscosity,paste appearance,be pasted and residues of a number of indicators as the response value of matrix PVA,Carbomer,the dosage of NP-800 was optimized to determine the optimal prescription of the matrix.Results: the optimum matrix formulation for optimal Tiegao tamoxifen gel carbomer 2.03 g,PVA2.46 g,NP-800 7.93 g.Conclusion: the gel paste was prepared according to the optimal matrix prescription with proper adhesion,good comfort,the indicators are in line with external preparation standard.