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Current Drug Delivery


ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

Pharmacokinetic and Pharmacodynamic Studies of Nifedipine Loaded Microspheres for the Treatment of Hypertension

Author(s): Chiman Lal*, Rajeev Garg and Ghanshyam Das Gupta

Volume 18, Issue 1, 2021

Published on: 10 August, 2020

Page: [65 - 70] Pages: 6

DOI: 10.2174/1567201817666200810111342

Price: $65


Purpose: The purpose of this research work was to evaluate the Pharmacokinetic (PK), Pharmacodynamic (PD), and the distribution pattern of mucoadhesive microspheres of nifedipine.

Methods: Firstly, the emulsion solvent evaporation technique was used to prepare the mucoadhesive microspheres. The microspheres were characterized by Fourier Transform Infrared Spectroscopy (FTIR) and in vivo studies were carried on Wistar rats.

Results: Blood samples of rats were withdrawal at 2, 4, and 8 h time interval, after the administration of Mucoadhesive microspheres of nifedipine (Mm-N) and the Saline solution of nifedipine (Ss-N) separately. The Area Under the Curve (AUC) of Mm-N was seven foaled and Cmax around four foaled high when compared with Ss-N with a significant difference P<0.005. Hypertension induced with DOCA (deoxycorticosterone acetate) and the Blood Pressure (BP) of hypertensive rats were recorded at 0, 0.5, 1, 2, 3, 4, 5, 6 h time interval after given Mm-N and Ss-N to different groups. The BP of rats was better control with Mm-N and regular after 2 h with high significant difference P<0.0001 however, the Ss-N have an insignificant difference with P>0.05. The Mm-N was distributed in the upper part of the Gastrointestinal Tract (GIT) after 8 h confirmed with the help of the fluorescence microscopic examination.

Conclusion: This study indicates that the nifedipine was present in the blood for a more extended period, and the blood pressure was easily controlled with mucoadhesive microspheres of nifedipine. Therefore, mucoadhesive microspheres of nifedipine would be an excellent alternative over conventional drug delivery for the treatment of hypertension.

Keywords: Hypertension, nifedipine, pharmacokinetic, pharmacodynamic, mucoadhesive microspheres, blood pressure.

Graphical Abstract
Erem, C.; Hacihasanoglu, A.; Kocak, M.; Deger, O.; Topbas, M. Prevalence of prehypertension and hypertension and associated risk factors among Turkish adults: trabzon hypertension study. J. Public Health (Oxf.), 2009, 31(1), 47-58.
[] [PMID: 18829520]
Ahmed, A.; Rahman, M.; Hasan, R.; Shima, S.A.; Faruquee, M.; Islam, T.; Haque, S.E. Hypertension and associated risk factors in some selected rural areas of Bangladesh. Int. J. Res. Med. Sci., 2014, 2(3), 925-931.
Mishra, C.; Kumar, S. Risk factors of hypertension in a rural area of Varanasi. Indian J. Prev. Soc. Med., 2011, 42(1), 101-111.
Abebe, S.M.; Berhane, Y.; Worku, A.; Getachew, A. Prevalence and associated factors of hypertension: a crossectional community based study in northwest ethiopia. PLoS One, 2015, 10(4)e0125210
[] [PMID: 25909382]
Alwan, A. Global status report on noncommunicable diseases 2010; World Health Organiz, 2011, p. 176.
Tabrizi, J.S.; Sadeghi-Bazargani, H.; Farahbakhsh, M.; Nikniaz, L.; Nikniaz, Z. Prevalence and associated factors of prehypertension and hypertension in Iranian population: the Lifestyle Promotion Project (LPP). PLoS One, 2016, 11(10)e0165264
[] [PMID: 27783691]
Killivalavan, P.; Kumaravelrajan, R.; Gopi, M.; Suba, V. Development of nifedipine timed-release spansule dosage form by extrusion-spheronization technology. Asian J. Pharm., 2017, 11(3), 192-200.
Webster, L.M.; Myers, J.E.; Nelson-Piercy, C.; Harding, K.; Cruickshank, J.K.; Watt-Coote, I.; Khalil, A.; Wiesender, C.; Seed, P.T.; Chappell, L.C. Labetalol versus nifedipine as antihypertensive treatment for chronic hypertension in pregnancy: a randomized controlled trial. Hypertension, 2017, 70(5), 915-922.
[] [PMID: 28893900]
Panchagnula, R.; Singh, R.; Ashokraj, Y. In vitro evaluation of modified release formulations of nifedipine from Indian market. Indian J. Pharm. Sci., 2007, 69(4), 556-561.
Wu, J.; Wang, B-j.; Wei, C-m.; Bu, F.; Guo, R. Pharmacokinetics of nifedipine sustained-release tablets in healthy Chinese volunteers. J. Chin. Pharm. Sci., 2007, 16(3), 192.
Okur, M.E.; Karantas, I.D.; Okur, N.U.; Siafaka, P.I. Hypertension in 2017: update in treatment and pharmaceutical innovations. Curr. Pharm. Des., 2017, 23(44), 6795-6814.
[] [PMID: 28969533]
Sood, A.; Panchagnula, R. Design of controlled release delivery systems using a modified pharmacokinetic approach: a case study for drugs having a short elimination half-life and a narrow therapeutic index. Int. J. Pharm., 2003, 261(1-2), 27-41.
[] [PMID: 12878393]
Cao, Q.R.; Choi, H.G.; Kim, D.C.; Lee, B.J. Release behavior and photo-image of nifedipine tablet coated with high viscosity grade hydroxypropylmethylcellulose: effect of coating conditions. Int. J. Pharm., 2004, 274(1-2), 107-117.
[] [PMID: 15072787]
Siafaka, P.I.; Caglar, E.S.; Papadopoulou, K.; Tsanaktsis, V.; Karantas, I.D.; Okur, N.U.; Karasulu, H.Y. Polymeric microparticles as alternative carriers for antidiabetic glibenclamide drug. Pharm. Biomed. Res., 2019, 5(4), 27-34.
Beri, C.; Sood, R.; Hemraj, G.A. Stomach specific mucoadhesive microspheres as controlled drug delivery system-a review. Int. J. Pharm. Pharm. Sci., 2013, 5(2), 21-26.
Andrews, G.P.; Laverty, T.P.; Jones, D.S. Mucoadhesive polymeric platforms for controlled drug delivery. Eur. J. Pharm. Biopharm., 2009, 71(3), 505-518.
[] [PMID: 18984051]
Serra, L.; Doménech, J.; Peppas, N.A. Engineering design and molecular dynamics of mucoadhesive drug delivery systems as targeting agents. Eur. J. Pharm. Biopharm., 2009, 71(3), 519-528.
[] [PMID: 18976706]
Lal, C.; Garg, R.; Gupta, G.D. Formulation and optimization by applying 32 full factorial design of mucoadhesive microspheres of nifedipine. Asian J. Pharm. Clin. Res., 2019, 12(6), 321-327.
Patel, J.; Patel, D.; Raval, J. Formulation and evaluation of propranolol hydrochloride-loaded carbopol-934P/ethyl cellulose mucoadhesive microspheres. Iran. J. Pharm. Res., 2010, 9(3), 221-232.
[PMID: 24363731]
Liu, Z.; Lu, W.; Qian, L.; Zhang, X.; Zeng, P.; Pan, J. In vitro and in vivo studies on mucoadhesive microspheres of amoxicillin. J. Control. Release, 2005, 102(1), 135-144.
[] [PMID: 15653140]
Madni, A.; Ekwal, M.; Ahmad, S.; Din, I.; Hussain, Z.; Muhammad Ranjha, N.; Imran Khan, M.; Akhlaq, M.; Ahmad Mahmood, M.; Zafar, H. FTIR drug-polymer interactions studies of perindopril erbumine. J. Chem. Soc. Pak., 2014, 36(6), 1064-1070.
Komati, S.; Swain, S.; Rao, M.E.B.; Jena, B.R.; Unnam, S.; Dasi, V. QbD-based design and characterization of mucoadhesive microspheres of quetiapine fumarate with improved oral bioavailability and brain biodistribution potential. Bull. Fac. Pharm. Cairo Univ., 2018, 56(2), 129-145.
Pervaiz, F.; Ahmad, M.; Li, L.; Murtaza, G. Development and characterization of olanzapine loaded poly(lactide-co-glycolide) microspheres for depot injection: in vitro and in vivo release profiles. Curr. Drug Deliv., 2019, 16(4), 375-383.
[] [PMID: 30588882]
Tao, Y.; Lu, Y.; Sun, Y.; Gu, B.; Lu, W.; Pan, J. Development of mucoadhesive microspheres of acyclovir with enhanced bioavailability. Int. J. Pharm., 2009, 378(1-2), 30-36.
[] [PMID: 19465102]
Jia, J.; Dong, C.; Zhang, W.; Cui, Y.; Liu, J. Evaluation of pharmacokinetic and pharmacodynamic relationship for oral sustained-release atenolol pellets in rats. J. Pharm. Biomed. Anal., 2011, 55(2), 342-348.
[] [PMID: 21353427]
Kanteenpan, P.; Dvrn, B. Devlopment and in vitro evaluation of mucoadhesive microspheres using pirenzepine. Asian J. Pharm. Clin. Res., 2018, 11(7), 296-302.
Shah, P.M.; Shah, J.S.; Maheshwari, D.G. Devlopment and validation RP-HPLC method for simultaneous estimation of valsartan and nifedipine in synthetic mixture. Asian J. Pharm. Tech. Innov., 2016, 4(17), 7-16.
Akcılar, R.; Turgut, S.; Caner, V.; Akcılar, A.; Ayada, C.; Elmas, L.; Ozcan, T.O. Apelin effects on blood pressure and RAS in DOCA-salt-induced hypertensive rats. Clin. Exp. Hypertens., 2013, 35(7), 550-557.
[] [PMID: 23387534]
Rao, K.V.; Venkatchalam, V. Sustained release mucoadhesive microcapsules of ramipril by ionic gelation technique: formulation design, optimization and characterization. Int. J. Pharm. Pharm. Sci., 2017, 9, 128-141.
Kulkarni, A.D.; Bari, D.B.; Surana, S.J.; Pardeshi, C.V. In vitro, ex vivo and in vivo performance of chitosan-based spray-dried nasal mucoadhesive microspheres of diltiazem hydrochloride. J. Drug Deliv. Sci. Technol., 2016, 31, 108-117.
Yedurkar, P.; Dhiman, M.K.; Petkar, K.; Sawant, K. Mucoadhesive bilayer buccal tablet of carvedilol-loaded chitosan microspheres: in vitro, pharmacokinetic and pharmacodynamic investigations. J. Microencapsul., 2012, 29(2), 126-137.
[] [PMID: 22047549]
Dhaliwal, S.; Jain, S.; Singh, H.P.; Tiwary, A.K. Mucoadhesive microspheres for gastroretentive delivery of acyclovir: in vitro and in vivo evaluation. AAPS J., 2008, 10(2), 322-330.
[] [PMID: 18523891]

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