Development Of Letrozole Tablet And Its Quality Standards

As the research and development of a reference listed drug (RLD) requires a lot of time and money and takes great risks,new drug research and development projects are currently decreasing around the world year by year.Pharmaceutical enterprises are focusing on the generic drugs in succession,which is of feature short period, low risk and handsome profit.To ensure the accuracy and reliability of analytical and testing results, it is necessary to validate the accuracy, rationality and feasibility of analysis methods.The method validation is the foundation of the establishment of quality standard. Analysis methods are firstly validated in this paper,including methodological validations of the dissolution, related substances and contents.According to the nature of the letrozole, this paper was designed to take the formulation screening through selecting excipients screened by excipient compatibility testing and those with good compatibility after referring to the RLD formulation and considering the usage of excipients in our country. In this paper, the lactose and the microcrystalline cellulose PH101were selected as fillers, starch as both filler and adhesive, sodium starch glycolate (CMS-Na) as disintegrant, magnesium stearate as lubricant, and colloidal silicon dioxide as glidant.Single factor test was adopted to screen out the ratios of fillers, types and contents of adhesives, glidant content and disintegrant content respectively. Particle fluidity, appearance of tablet, hardness, friabibity, disintegration time and dissolution curve were taken as indicators. Formula12was determined, namely, a letrozole tablet contains2.5mg letrozole,59mg lactose,17.5mg microcrystalline cellulose PH101,17.5mg starch,4mg sodium starch glycolate,1mg colloidal silicon dioxide and1mg magnesium stearate.Single factor test was adopted to optimize the preparation technology, including addition amount of adhesive, tablet hardness, coating weight and particle size. The production process of the letrozole tablet was developed, from laboratory scale to industrial scale. The production process includes following major steps:mixing, preparing the damp mass, granulating, drying, milling, general mixing, tabletting, coating and packaging. Process steps which may have impact on the preparation quality during the preparing process are also investigated in this paper.