Chronotherapeutic drug delivery Systems – an approach in the management of diseases based on circadian rhythm

Abstract

Chronotherapeutic systems are based completely on circadian needs and response of the body and the need of the drug to be in its maximum concentrations at a particular time of the day, the fact being supported by many of the ailments which produce the related symptoms at a particular time of the day. Here the approaches have been utilized to prepare a delivery system as per the rhythmic cycles of the human body. These rhythmic cycles run various body functions in human beings such as metabolic process, physiology of man, behavior, sleep patterns, hormone production. The people of diabetes mellitus are observed to have increased level of glucose in the blood, instantly after taking the food as compared to other timings during the day and night. The pulsatile response i.e. delivering the active pharmaceutical ingredient (API) after a lag time so as to follow a complete and rapid drug release pattern. These approaches are also known as period scheduled systems since the active pharmaceutical ingredient (API) which has been released is free of the surroundings [1-3]. These approaches are important for systems that have high first-pass effect and for the drugs which are best absorbed in the gastrointestinal tract, going in small intestine; in colon, and in the situations where night dose is required. Drug delivery system which is orally controlled are often used in practice as they are more convenient dosage form. In this approach the release of the drug takes place within the absorption site for prolonged time state. Being having a response of passive process towards extraneous variations, the circadian cycles are controlled by endogenous biological clocks. For example, in animals, a pacemaker is the suprachiasmatic nuclei (SCN) that observes various non-therapeutic processes lightening therapy, sleepiness and rhythmic therapy) and therapeutic processes of various diseases influences the circadian rhythms internally [4-6]. The patterns of circadian have been well observed. The final observation of different studies related top epidemiology depicts a danger of various conditions during the cycle of 1 day. Now treating various diseases with immediate action of drug is not possible if the disease is having symptoms which are prevalent in the night time or during day time, so an approach that is modified process of releasing the drug. To optimize an approach with regard to efficiency, patient compliance chronotherapeutic formulations have been practiced upon which are considered to be potential in delivering the drug with therapeutic levels. Chronotherapeutic diseases include asthma, diabetes, hypertension, glaucoma, rheumatoid arthritis and cancer.  Pharmacological aspects Chronotherapeutic systems are intended to be taken or administered at a specific time of the day typically bed time due to the symptom presentation of the conditions following rhythmic behavior (asthma, allergic rhinitis, rheumatoid arthritis, angina pectoris, congestive heart failure, and hypertension) being prominent in the middle of the night or in the morning hours[7]. There are also certain conditions such as osteoarthritis for which the painful symptoms worsen in the evening hours for which the development of such systems may not be necessary as an immediate release tablet would suffice. Inadvertently if a patient takes the medicine in the morning hours which is intended to be taken at bed time, then the purpose of formulating the dosage form for achieving the said objective becomes futile due to obvious reasons. What is meant by this is an ideal chronotherapeutic formulation should be such that it releases the drug in response to a change in the body conditions, that is, the drug release should trigger in response to the change in physiology of the body. For example, if a patient suffers high blood pressure in the morning hours, the increase in the blood surge should automatically trigger the drug release from a chronotherapeutic formulation already in the body [8-10]. Literature review has been done from database including pubmed, science direct scopus and elsevier using key words: chronotherapy, time released systems and chronopharmaceuticals. This review aims to discuss the need for chronotherapy in drug deliver, its pharmacological aspects along with some formulation technologies used in chrono pharmaceuticals. The expected outcome of the proposed review work is that it offer the way to administer the  medication in comfortable, convenient and in noninvasive manner which offer the advantage of dose reduction, minimization of drug resistance and improved bioavailability over conventional, sustained and controlled- release products drug delivery system.