Abstract

FORMULATION APPROACHES TO PULSATILE-RELEASE CHRONOTHERAPEUTICAL DRUG DELIVERY SYSTEM WITH MONTELUKAST SODIUM

Popova T., Petkova V. and Dimitrov M.

ABSTRACT

Since the occurrence of asthma attacks is not random during the day (asthma bronchoconstriction incidents are 50-100 time more common between midnight and early morning hours with peak of bronchoconstriction at 4.00 am), synchronizing drug release to the body’s circadian rhythms (chronotherapy) in the treatment of asthma has been the desired goal of many drug delivery companies for at least two decades. This can be accomplished by creation of chronopharmaceutical system which can release the drug rapidly immediately after well-defined lag-time – pulsatile release drug delivery system. Desired time-controlled release rate can be achieved in many ways, but press-coating technology is one of the most promising techniques. That’s why for the purpose of the present study – formulation a chronopharmaceutical system with montelukast sodium (MS) for treatment of nocturnal asthma, eight different formulations press-coated tablets, containing immediate release tablet core and outer shell, capable of obtaining sufficient lag-time, were prepared and evaluated. Increasing in particle size of ethylcellulose (EC), decreasing in amount of outer shell and inclusion of hydrophilic polymer sodium alginate leads to shorter lag-time. Sufficient lag-time (above two hours) provides formulations with smaller particle size of EC, higher amount of outer shell and lower concentration of sodium alginate. These formulations exhibit the desired chronotherapeutical release profile – taken before bedtime they deliver montelukast between midnight and early morning hours when asthma incidents are with higher frequency.

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