Abstract
Core tip:
The time rhythm of the human body is associated with the occurrence and development of many diseases. Kinds of diseases of particular onset biorhythm provided the room for the development of chronopharmacological drug delivery systems. Metoprolol tartrate (MT), a medicine commonly used for treatment of cardiovascular diseases in clinic, was selected as model drug to develop a time-controlled explosive pulsatile tablet. The prepared MT pulsatile tablets showed a drug release lag time of 7.10 h in vitro perfectly consistent with the absorption lag time of 7.04 h in vivo, which ensured the pulsatile tablet a promising chronopharmacological drug delivery system for MT to prevent and treat the peak attack of hypertension and angina pectoris early in the morning.
Abstract:
Background The time rhythm of human body is associated with the occurrence and development of many diseases. Kinds of diseases of particular onset biorhythm provided the room for the development of chronopharmacological drug delivery systems.
Aim In this work, the drug release and pharmacokinetics behavior of metoprolol tartrate (MT) pulsatile tablet developed in our lab was investigated to figure out its feasibility of convenient drug taking to exert effective chronotherapy for cardiovascular diseases like hypertension and angina pectoris.
Methods The in vitrorelease behavior of MT pulsatile tablets was investigated by using basket method. The appearance and morphology of MT pulsatile tablets during drug release was observed by naked eye and
scanning electronic microscope, respectively. In vivo pharmacokinetics performance was studied in New Zealand rabbits.
Results The lag time of MT pulsatile tablets was approximately 7 h in vitro, and a fast release was observed thereafter, with more than 90% releasing within 10 min. The pharmacokinetics study in rabbits demonstrated a perfect consistence in the absorption lag time of 7.04 ± 0.29 h in vivo. Compared with the marketed conventional tablet, the MT pulsatile tablet showed a bioequivalence in absorption extent with a relative bioavailability of 110.04%, but not in absorption rate.
Conclusion The designed lag time of 7 hours enabled the MT pulsatile tablets to achieve effective chronotherapy for cardiovascular diseases like hypertension and angina pectoris with a high attack rhythm around 4:00-6:00 A.M by giving medicine conveniently around 22:00 P.M. the night before.
Keywords
Full Text:
References
Erhard H. Chronobiology in the endocrine system. Adv Drug Deliv Rev. 2007; 59(9): 985-1014.
Michael HS, Nicholas AP. Chronobiology, drug delivery, and chronotherapeutics. Adv Drug Deliv Rev. 2007; 59(9-10): 828-51.
Björn Lemmer. Chronopharmacokinetics: Implications for Drug Treatment. J Pharm Pharmacol. 1999; 51(8):887-90.
Mandal A S, Biswas N, Karim K M, Guha A, Chatterjee S, Behera M, et al. Drug delivery system based on chronobiology-A review. J Controlled Release. 2010; 147(3): 314-25.
Khan Z, Pillay V, Choonara YE, du Toit LC. Drug delivery technologies for chronotherapeutic applications. Pham Devel Tech. 2009; 14(6): 602-12.
Maroni A, Zema L, Curto MDD, Loreti G, Gazzaniga A. Oral pulsatile delivery: Rationale and chronopharmaceutical formulations. Int J Pharm. 2010; 398(1-2): 1-8.
Roy P, Shahiwala A. Multiparticulate formulation approach to pulsatile drug delivery: Current perspectives. J Control Release. 2009; 134(2):74-80.
Gazzaniga A , Palugan L, Foppoli A, Sangalli ME. Oral pulsatile delivery systems based on swellable hydrophilic polymers. Eur J Pharm Biopharm. 2008; 68(1):1-18.
Fan TY, Wei SL, Yan WW, Chen DB, Li J. An investigation of pulsatile release tablets with ethylcellulose and Eudragit L as film coating materials and cross-linked polyvinylpyrrolidone in the core tablets. J Control Release. 2002; 77(3): 245-51.
Bussemer T, Dashevsky A, Bodmeier R. A pulsatile drug delivery system based on rupturable coated hard gelatin capsules. J Control Release. 2003; 93(3): 331-9.
Usha YN, Gopal VS, Yogendra N, Ranjith KA, Srinivas M, Sreenivasa MR, et al. Chronotherapeutic drug delivery for early morning surge in blood pressure: A programmable delivery system. J Control Release. 2009; 136(2): 125-31.
Gohel MC, Manhapra SG. Modulation of active pharmaceutical material release from a novel 'tablet in capsule system' containing an effervescent blend. J Control Release. 2002; 79(1-3): 157-64.
Wang C, Chen F, Heng PW, Li JZ, Li X, Ye GH, et al. A Novel Time-Controlled Release System Based on Drug-Resin Complexes and Elementary Osmotic Pump. Chem Pharm Bull. 2008; 56(4): 457-63.
Chu LY, Liang YJ, Chen WM, Ju XJ, Wang HD. Preparation of glucose-sensitive microcapsules with a porous membrane and functional gates. Colloid Surface B. 2004; 37(1-2): 9-14.
Oh KS, Han SK, Choi YW, Lee JH, Lee JY, Yuk SH. Hydrogen-bonded polymer gel and its application as a temperature-sensitive drug delivery system. Biomaterials. 2004; 25(12): 2393-8.
Nakayama M, Okano T, Miyazaki T, Kohori F, Sakai K, Yokoyama M. Molecular design of biodegradable polymeric micelles for temperature-responsive drug release. J Control Release. 2006; 115(1): 46-56.
Satarkar N S, Hilt J Z. Magnetic hydrogel nanocomposites for remote controlled pulsatile drug release. J Control Release. 2008; 130(3): 246-51.
Saslawski O, Weingarten C, Benoit JP, Couvreur P. Magnetically responsive microspheres for the pulsed delivery of insulin. Life Sci. 1988; 42(16):1521-8.
Kwok CS, Mourad PD, Crum LA, Ratner BD. Self-assembled molecular structures as ultrasonically-responsive barrier membranes for pulsatile drug delivery. J Biomed Mater Res. 2001; 57(2):151-64.
Bertil W, Leon L, Tomas K, Hans T, Rein V, Ake H. Circadian variation of heart rate variability and the rate of autonomic change in the morning hours in healthy subjects and angina. Int J Cardiol. 2001; 79 (1):61-9.
Kolettis T M, Papathanasiou A, Tziallas D, Milionis HJ, Kastanioti CK, Achenbach K. Afternoon nap, meal ingestion and circadian variation of acute myocardial infarction. Int J Cardiol. 2008; 123(3): 338 -40.
Lemmer B. The importance of circadian rhythms on drug response in hypertension and coronary heart disease-from mice and man. Pharmacol Ther. 2006; 111(3): 629-51.
Elliott WJ. Cyclic and circadian variations in cardiovascular events. Am J Hypertension. 2001; 14(9): S291-5.
Li S, Wang X, Fu S, Li L, Wang K, Song Y, et al. HPLC-UV method for the determination of metoprolol in rabbit plasma and its application in pharmacokinetic study. Chin J Hosp Pharm. 2012; 32(10): 741-4.
Refbacks
- There are currently no refbacks.
Copyright (c) 2020 Journal of Pharmaceutical and Biomedical Sciences
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.