FORMULATION DEVELOPMENT AND EVALUATION OF CHRONOMODULATED DRUG DELIVERY SYSTEM BY ZAFIRLUKAST Original Article N. SHIVA KRISHNA 1* , B. JAYANTHI 2 , A. MADHUKAR 3 1 Department of Pharmaceutics, St Marys Group of Institutions, Deshmukhi (V) Pochampally and Batasingaram (M) Near Ramoji Film City Hayathnagar (M) Ranga Reddy (Dist.) 508284, Hyderabad, Telangana, India, 2 Department of Pharmaceutics (Drug Delivery System), Annamalai University, Annamalainagar 608002, Tamil Nadu, India, 3 Department of Pharmacy, MRM College of Pharmacy, Chinthapalliguda, Ibrahimpatnam, Hyderabad 501510, Telangana, India Email: shivakrishnapharmacy@gmail.com Received: 08 Apr 2021, Revised and Accepted: 27 May 2021 ABSTRACT Objective: The main objective of the present study was to formulate and evaluate a time-controlled single-unit oral pulsatile drug delivery system containing Zafirlukast for the prevention of nocturnal asthma attacks. To provide time-scheduled drug release for Asthma disease. It is used for preventing asthmatic attacks at early morning. Pulsatile release dosage form is increasing patient compliance by reducing the dosing frequency, especially in the early morning. Methods: Core tablets were prepared by incorporating different concentrations of natural and synthetic super disintegrants. Drug-containing core tablets (ZC1-ZC15) with different compositions of natural super disintegrants (Plantago ovata seed powder, Locust bean gum) synthetic super disintegrants (Sodium starch glycolate (SSG), Cross carmellose sodium (CCS), Crospovidone (CP)) were prepared by direct compression technique. The core tablets were subjected to pre-formulation, physicochemical and In vitro drug release studies. The fast disintegrating core tablet formulation was selected and press-coated tablets (P1-P11) were prepared with different compositions of hydrophobic polymers Eudragit RS100, Eudragit RL 100, Ethylcellulose and hydrophilic polymers Hydroxypropyl methylcellulose K4M, K100M. The optimized formulation was selected and quantified based on in vitro drug release profile in simulated gastric and intestinal fluids. Results: The pre and post-compression parameters of tablets were also found to be within limits. Formulation ZC5 with 16 mg of Locust bean gum showed the least disintegrating time, i.e., 22.13 sec, and was selected as the best immediate release core tablet. The press-coated tablet formulation P8 having 62.5 mg Eudragit RS100 and 62.5 mg of HPMC K4M in ratio 1:1 over the core tablet ZC5 showed rapid and drug release nearly after 4 h lag time and 98.86 % up to 12 h. Accelerated stability studies of the optimized formulation P8 indicated no significant difference in release profile after 3 mo. Conclusion: The in vitro dissolution study showed that lag time before drug release was highly affected by the coating amount level and nature of coating polymer used. Time-controlled pulsatile release tablets can be prepared using press-coating techniques. Keywords: Pulsatile formulation, Zafirlukast, Chronomodulated drug delivery system, Compression coated tablets © 2021 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/) DOI: https://dx.doi.org/10.22159/ijap.2021v13i4.41734. Journal homepage: https://innovareacademics.in/journals/index.php/ijap INTRODUCTION The time-controlled and pulsatile release is increasingly being considered as desirable modes of drug delivery [1-3]. A pulsatile drug delivery system (PDDS) can be de fined as a system where the drug is released suddenly after a well-defined lag time according to the circadian rhythm of the disease [4, 5]. PDDS can be classi fied according to the pulse-regulation of drug release into three main classes; time-controlled pulsatile release (single or multiple unit system), internal stimuli-induced release, and external stimuli- induced pulsatile release systems [4, 6]. PDDS can also be classi fied according to the dosage form into three main types; capsules, pellets, and tablets. The tablet system consists of two different core tablets, containing the active ingredient, the outer top cover layer of a soluble polymer, and insoluble polymer [4, 7]. The release of some drugs is preferred in pulses. A single dosage form provides an initial dose of the drug followed by one release-free interval, after which a second dose of the drug is released, which is followed by an additional release-free interval and pulse of drug release [8]. Depending upon the physiological and physiopathological changes of circadian rhythmicity, nocturnal symptoms and overnight decrements in lung functions are a common part of the asthma clinical syndrome [9]. Circadian changes are seen in normal lung function, which reaches a low point in the early morning hours. The dip is particularly pronounced in people with asthma, because bronchoconstriction and exacerbation of symptoms vary in a circadian fashion, a sharp increase in asthmatic attacks during early morning hours. For such conditions a drug delivery system administered at bedtime, but releasing the drug during morning hours, would be an ideal one [10]. The main objective of the study was to develop a time-controlled release formulation based on a press coat technique using rate- controlling natural (hydrophilic) polymers and synthetic (hydrophobic) polymers and Zafirlukast as a model drug. The intention was to maintain lag time 3-4 h. As the symptoms of asthma are experienced in the early morning hours. The incorporation of the drug as an immediate release formulation in the core is proposed to provide the drug to the patient at the right time of asthmatic risk. The release is expected as a burst, i. e at once pulsatile drug delivery of Zafirlukast after a lag time [11-13]. The rationale for the development of an appropriate formulation is to provide the drug at the right time, i.e. early morning. The formulation has a rapid- release core tablet of Zafirlukast with super disintegrants [14]. MATERIALS AND METHODS Materials Zafirlukast was Provided by Sura Labs, Dilsukhnagar. Plantago ovata seed powder was Purchased from the local market. Sodium starch glycolate Purchased from SD Fine Chemicals, Mumbai. Crospovidone, Locust bean gum, and Croscarmellose sodium were Purchased from R. K. Enterprises, Ghaziabad. Eudragit RS100 was Purchased from Evonik Industries, Mumbai, Maharashtra. Eudragit RL 100 was Purchased from Evonik Industries, Mumbai, Maharashtra. Ethylcellulose was Purchased from CDH chemicals, New Delhi, India. HPMC K4M and HPMC K100M were Purchased from Colorcon Asia Pvt. Ltd., Goa. Mannitol, Mg Stearate, Talc, and PVP K 30 were purchased from SD Fine Chemicals. Mumbai, Maharashtra. Aerosil was purchased from Reachem labs, New Delhi, India. MCC was purchased from Sigma Chemicals, Bangalore, India. International Journal of Applied Pharmaceutics ISSN- 0975-7058 Vol 13, Issue 4, 2021