Research And Development For Donepezil Hydrochloride Orally Disintegrating Tablets

In April 2012, the United States Food and Drug Administration (US FDA) released Quality by Design (QbD) for Abbreviated New Drug Applications (ANDAs):An Example for Immediate-Release Dosage Forms and An Example for Modified Release Dosage Forms. Those two documents focus on how to apply QbD as a good practice in research and development, introducing the importance of project design in the product quality of a generic drug, discussing its concept and composition in detail, as well as the implementation tools and research methodology. This document can be considered as a scientific guideline, with both skeletal and elaborate information, for research and development, registration and application review of generic formulations for pharmaceutical industry.Donepezil HCL (Donepezil hydrochloride) orally disintegrating tablet is one of the fast release formulations. Therefore, it is suitable for formulation development utilizing the QbD approach, as well as can be considered as a model for the development of conventional fast release formulations.The orally disintegrating tablet is advantageous over conventional one, as it does not require patients to drink water for swallowing the tablet. These tablets can be either dissolved or disintegrated in the presence of patient's saliva. In addition, patients can dissolve/disintegrate the tablets in water prior to taking the medication, suitable for elderly, children and patients with difficulty in swallowing or limited access to drinkable water. Donepezil hydrochloride is for the treatment of Alzheimer's disease, therefore the product development as orally disintegrating tablets.The current research focused on developing the donepezil hydrochloride orally disintegrating tablets according to the published guideline with the excipients and equipment. A series of work were performed, including project design, excipient screening, component compatibility study, formulation development, optimization, production of exhibition and registration batches, etc.Therefore, the formulation was successfully developed, complying with the US pharmacopeia (i.e. USP35-NF30).In addition, Comparing with wet granulation process, the formulation was developed by direct compression process commonly used in the pharmaceutical industry. Such a simple process facilitates the in-process control, ideal for scale-up for industrial production.