Application of Tablet in Tablet technique to design and characterize immediate and modified release tablets of Timolol maleate

Abstract

Hypertension is one of the major causes of mortality in the world. The non-selective -β-blocker which includes Timolol maleate (TM) is usually used in hypertension, at a given dose of 10–40 mg. The present research aims to design a tablet-in-tablet (TIT) formulation as a single-unit dosage form to achieve modified and rapid drug release. Wet granulation was used to create the inner core modified release tablet utilising the release modifying agent's Sodium alginate (SA) and Hydroxypropyl methylcellulose (HPMC K4M). The impact of independent factors, SA and HPMC K4M, in different percentages of w/w, which affect the in vitro drug release and swelling index, was investigated using a 32 complete factorial design. The TM outer instant-release shell, which was made using croscarmellose sodium and Microcrystalline cellulose (MCC) in three distinct sizes, was press-coated onto the optimised inner core tablet. The core and outer shell tablets are within acceptable ranges for several physicochemical properties. No indication of interactions between drugs, polymers, and excipients was found in the Fourier transform infrared (FTIR) and Differential scanning calorimetry (DSC) investigations. The inner core tablet's formulation F6 achieves a 96.38% in vitro drug release at 24 h and a swelling index of 52.7%. The TIT-2 was, however, considered as the final tablet-in-tablet formulation because contains fewer excipients and shorter disintegration time than TIT-3.

Keywords

• Tablet-in-tablet
• Modified release
• PXRD
• DSC
• Core tablet
• Outer shell