Core and cup tablet of Salbutamol sulphate for chronotherapeutic delivery was prepared to increase the effectiveness of drug by using optimization technique.The formulation contains three components a core tablet, impermeable layer and soluble hydrophilic polymer layer. The core tablet contains salbutamol sulphate drug and other excipients, impermeable layer is made up of Ethyl cellulose (EC), and the polymer layer is made of HPMC 15cps and HPMC 50cps. In this work the key ingredients like HPMC 15cps and HPMC 50cps were optimized by using 32 Factorial designing in this various proportions of HPMC 15cps and HPMC 50cps (polymers) were used in different levels in the preparation of core in cup tablet.