Study On Preparation Technology And Quality Standard Of Doxepin Hydrochloride Tablets

Doxepin hydrochloride tablet(specification:3 mg)is a common tablet developed by Somaxon Pharmaceutical Co.,Ltd.with the trade name of silenor.It is used to treat adult insomnia.There is no imitation or import in China.The purpose of this paper is to study the prescription and preparation process of doxepin hydrochloride tablets(specification:3 mg),study the quality and stability of the products,determine the rationality of the prescription and the feasibility of the preparation process.It provides a basis for the industrial production of this product.This paper is fully investigated the original research products,designed the prescription components of the original research products,adjusted the dosage of excipients in the prescription,and the prescription was determined through the experimental discussion of influencing factors.The prescription composition(1000tablets)is:Doxepin hydrochloride 3.39 g,microcrystalline cellulose ph102 81.21 g,magnesium stearate 0.90 g,silica 4.50 g.According to the analysis of physical and chemical properties and functions of auxiliary materials,this paper is determined to use the mixed powder direct pressing process:first,half of the screened API and microcrystalline cellulose ph102 are mixed,after mixing evenly,add the remaining half of API and microcrystalline cellulose ph102 in sequence and mix evenly.The mixture and surplus accessories are set up in a three dimensional motion mixer.The speed is 6 rpm and the powder is mixing 25 min.Determine the intermediate content to confirm the theoretical tablet weight.Rotary tablet press uses the 6 mm shallow concave stamping to press the tablet.The tablet pressing speed is controlled between 10-35 rpm,the hardness shall be controlled between 35～60 N.In this paper,three batches of pilot test are carried out with the pilot test equipment with the same principle as the production workshop,15000 pieces per batch,and the process conditions are determined suitable for the pilot test equipment.The quality of the pilot product is studied.The quality standard is:the product is white to almost white,the dissolution result is more than 75%of the marked amount,the content uniformity is A+2.2S<15,and the doxepin hydrochloride(C19H21NO)is calculated as 90.0%～110.0%of the marked amount.There is no significant difference between the original product and the pilot product according to the above quality standards.The influencing factors and stability experiments were carried out on the pilot test samples.The influencing factors were investigated under the conditions of light,high temperature and high humidity.Under the conditions of high temperature and light,the properties,content and dissolution of the product did not change except that the impurity level increased slightly.The stability test investigated the accelerated test(temperature 40 ℃±2 ℃,relative humidity 75%±5%),long-term test(temperature 25 ℃±2 ℃,relative humidity 60%±10%)and long-term test(temperature 30 ℃±2 ℃,relative humidity 65%±5%).Under the 6-month accelerated test and long-term test conditions,except for the slight increase of impurity level,the properties,content and dissolution did not change significantly.The results show that the main inspection indexes of the pilot product are within the qualified range.The quality standard can better control the product quality.The research results of this paper show that the formulation design of doxepin hydrochloride tablets is reasonable,the preparation process is feasible,and the product stability is good,which meets the standard of the original product,and provides a solid theoretical and experimental basis for the industrial production of doxepin hydrochloride tablets(3 mg).There are 8 figures,67 tables and 53 references in this paper...