Optimization and Development of a Core-in-Cup Tablet for Modulated Release of Theophylline in Simulated Gastrointestinal Fluids

Abstract

A triple-layer core-in-cup tablet that can release theophylline in simulated gastrointestinal (GI) fluids at three distinct rates has been developed. The first layer is an immediate-release layer; the second layer is a sustained-release layer; and the last layer is a boost layer, which was designed to coincide with a higher nocturnal dose of theophylline. The study consisted of two stages. The first stage optimized the sustained-release layer of the tablet to release theophylline over a period of 12 hr. Results from this stage indicated that 30% w/w acacia gum was the best polymer and concentration to use when compressed to a hardness of 50 N/m². The second stage of the study involved the investigation of the final triple-layer core-in-cup tablet to release theophylline at three different rates in simulated GI fluids. The triple-layer modulated core-in-cup tablet successfully released drug in simulated fluids at an initial rate of 40 mg/min, followed by a rate of 0.4085 mg/min, in simulated gastric fluid TS, 0.1860 mg/min in simulated intestinal fluid TS, and finally by a boosted rate of 0.6952 mg/min.

Key Words:

• Dissolution
• Modulated release
• Nocturnal asthma
• Tableting