The Preparation Process And Quality Assurance Of A New Oncology Product Gl-501

GL-501 is a novel,potent,orally selective histone deacetylase inhibitors(HDACI),pharmacologically classified as oncology drugs.GL-501 is an innovative drug.Our company has signed an agreement with Selix Pharmaceuticals to obtain the exclusive rights in China.GL-501 is now undergoing phase III clinical study.To satisfy the request of future industrial production,we have optimized our licensed-in preparation process without changing synthesis route,excipients and key process parameters.Firstly,we have optimized the experimental process,the reaction time of step one and two intermediates has reduced form both twelve hours to fifteen minutes and four hours separately.The docoloration time of refined step has reduced form twelve hours to eight hours.These have much simplifiedexperimental operation and reduced time under the condition of guaranteeing the quality of product.Then we have completed three scale-up batches production.All the experimental optimization study and enlarge production results reveal the product quality is controllable,the limit of impurited were below 0.1%.Stress test reveal that the product could behygroscopic and should be stored sealed.Meanwhile,we have transfered the formulation process and studied the particle size of active pharmaceutical ingredient,which may influence the dissolution of the final product,and the feasibility of different resourced excipients were verified in the compatibility test.Result showed that micro-powder of raw material is necessary in the production processbecause it could obviously improve the dissolution of the final product.GL-501 could be slightly degraded when mixed with carboxymethyl starch sodium in high temperature environment.To avoid the possible risk,alkaline stabilizer potassium carbonate should be added in GL-501 tablet core prescription.We have also transferred the quality specification and methods and tested three batches enlarged products.The dissolution curve was the same in three dissolution mediums,the dissolubility has reached more than 85%in ten minutes.Three months acceleration and long-term stability showed no significant change occurred in Critical Quality Attribute,the product quality is stable.This study successfully completed pre-clinical technology transfer and provides a basis for the registration in China.