Abstract

COMPARISON OF SINGLE- AND MULTI-STAGE EXTRUSION VERSUS PRESS-COATING TECHNIQUE IN FORMULATION OF MODIFIED-RELEASE TABLETS WITH THEOPHYLLINE

Popova T., Petkova V*. and Dimitrov M.

ABSTRACT

Theophylline has been used in the treatment of respiratory diseases such as asthma and COPD for more than 80 years. It is still a common reported drug, especially for patients with a pronounced clinical picture due to its easy application and low price. The bronchodilating action of theophylline makes the drug useful in the chronic treatment of bronchial asthma, but its narrow therapeutic concentration range and variable pharmacokinetics make dosing management of the drug difficult, which requires utilization of modified release drug dosage forms. One approach to increase the effectiveness of pharmacotherapy is to administer medications while they are most effective and/or tolerable. The principles of chronotherapy can be applied by designing and characterizing drug delivery systems that synchronize drug release with the rhythm of disease activity. Time-controlled release rate can be achieved in many ways, but press-coating technology and multiple-unit pellet systems (MUPS) are one of the most promising techniques. For the purpose of the present study – development of chronopharmaceutical system for treatment of nocturnal asthma, nine formulations tablets prepared from pellets via single- (E1-1-E3-1), two- (E1-2-E3-2) and three-stage (E1-3-E3-3) extrusion and nine formulations single- (T1-1-T3-1), two- (T1-2-T3-2) and three-layered (T1-3-T3-3) press-coated tablets using different polymer blends were prepared, characterized and compared. Formulations with HPMC release slower than formulations with CMC Na and increasing viscosity grade of HPMC, leads to decreasing in release rate. Moreover, fastest is the release rate from single-extruded pellets and slowest – from three-stage extruded pellets. Comparing method of preparation – press-coating technique gives faster release of API than multi-stage extrusion. Among all formulations, formulations E1-3, E2-3, E3-3 and T2-3 exhibit the desired chronotherapeutical release profile – taken before bedtime they deliver API between midnight and early morning hours when asthma incidents are with higher frequency.

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