The Development Of Tamoxifen Citrate Gel

Infantile hemangioma is the most common cancer developed in childhood with a incidence rate about as high as 3%. Proliferating hemangioma may have complications, such as ulcers, bleeding, infection, thrombocytopenia, heart failure and so on. Clinical treatments, including surgery, laser, freezing, radiation therapy, intratumoral injection, etc, have some side effects. With the development of molecular biology, the scholars found that the pathogenesis of hemangioma may be too closely related to the high estrogen. It is reported that Tamoxifen Citrate as estrogen receptor antagonist, has a certain therapeutic effect on vascular tumors. In the thesis Tamoxifen Citrate as a model drug, was developed for topical skin gel that provide a new clinical drug formulations for the treatment of infantile hemangioma.In this thesis, UV spectrophotometry and HPLC for the content determination of Tamoxifen Citrate gel were established, and HPLC for the content determination of in vitro percutaneous penetration test was established. The methodology was investigated separately, such as precision, stability, recovery, etc, the results were consistent with the relevant requirements of Chinese Pharmacopoeia.The method for in vitro percutaneous penetration test was established, and the penetration enhancer of Tamoxifen Citrate gel was selected out according to the test. In vitro percutaneous penetration test used drugs percutaneous diffuse tester, vertical Franze diffusion cell, dialysis membrane was acted as osmotic membrane,50% ethanol saline solution was acted as acceptable solution. Steady state permeability rate JS, delay time T, and permeability enhancement ratio ER was acted as the indicator, the three penetration enhancers propylene glycol (10%～25%), Azone (1%～5%) and oleic acid (1%～5%) were selected. The results showed that 15% propylene glycol can best promote percutaneous penetration with the steady-state permeability rate JS 72.389μg/cm2/h, delay time T 1.835h, permeability enhancement ratio ER 1.73. Therefore, 15% propylene glycol was finally chosen as the penetration enhancer.Based on the single factor investigation, cumulative permeation amount as an indicator, using the orthogonal design method optimize and determine the prescription and preparation process of Tamoxifen Citrate gel. And its quality was investigated, such as character, power of hydrogen, viscosity, content and in vitro release degree, etc. It is white, translucent, gelatinous, semi-solid material, uniform and exquisite appearance, better coating ductility, pH about 6.2, viscosity between 70～80Pa·S, content of Tamoxifen Citrate about 10mg / g, cumulative permeation amount in vitro between 300～400μg/cm2. Using impact factor tests (including the high temperature test, high humidity test and strong light exposure test), accelerated test and long-term test carried out stability studies. The results showed that high temperature and strong light had a greater influence on Tamoxifen Citrate gel, it is required to avoid high temperature and light for storage, high humidity had almost no effect on it; In the 6 months accelerated test and the 12 months long-term test, all the indexes of Tamoxifen Citrate gel found no significant change, and its quality is stable. Further long-term tests are still ongoing.Safety studies were conducted by using rabbit skin irritation test, which showed that Tamoxifen Citrate gel had no skin irritation on rabbit. Further safety studies should be evaluated by sensitivity tests.In this thesis, reasonable, feasible and stable prescription and preparation process of Tamoxifen Citrate gel was developed, and the quality of the obtained gel is stable with no skin irritation. It is required to avoid high temperature and light for storage. It provide a new clinical drug formulation for the treatment of infantile hemangioma.