3 (2) Factorial Design Assisted Crushed Puffed Rice-HPMC-Chitosan based Hydrodynamically Balanced System of Metoprolol Succinate

Author(s): Shashank Soni*, Veerma Ram, Anurag Verma

Journal Name: Drug Delivery Letters

Volume 10 , Issue 3 , 2020

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Abstract:

Introduction: Hydrodynamically balanced system (HBS) possesses prolonged and continuous delivery of the drug to the gastrointestinal tract which improves the rate and extent of medications that have a narrow absorption window. The objective of this work was to develop a Hydrodynamically Balanced System (HBS) of Metoprolol Succinate (MS) as a model drug for sustained stomach specific delivery.

Methods: Experimental batches were designed according to 3(2) Taguchi factorial design. A total of 9 batches were prepared for batch size 100 capsules each. Formulations were prepared by physically blending MS with polymers followed by encapsulation into hard gelatin capsule shell of size 0. Polymers used were Low Molecular Weight Chitosan (LMWCH), Crushed Puffed Rice (CPR), and Hydroxypropyl Methylcellulose K15 M (HPMC K15M). Two factors used were buoyancy time (Y1) and time taken for 60% drug release (T60%; Y2).

Results: The drug excipient interaction studies were performed by the thermal analysis method which depicts that no drug excipient interaction occurs. In vitro buoyancy studies and drug release studies revealed the efficacy of HBS to remain gastro retentive for a prolonged period and concurrently sustained the release of MS in highly acidic medium. All formulations followed zero-order kinetics.

Conclusion: Developed HBS of MS with hydrogel-forming polymers could be an ideal delivery system for sustained stomach specific delivery and would be useful for the cardiac patients where the prolonged therapeutic action is required.

Keywords: Response surface methodology, hydrodynamically balanced system, taguchi factorial design, buoyancy time, T60% drug release, stomach specific delivery.

[1]
Mohammad, H. Gastroretentive Drug Delivery System Comprising An Extruded Hydratable Polymer U.S. Patent 8,586,083, issued November 19, 2013.
[2]
Tanaka, M. Kazuhiro, Sato.; Erika, K.; Shingo, K.; Takashi, H.; Kazuki, F. Design of biocompatible and biodegradable polymers based on intermediate water concept. Polym. J., 2015, 47(2), 114-120.
[http://dx.doi.org/10.1038/pj.2014.129]
[3]
Hunkeler, D.; Klaus, E.; Julien, A. Gastro-retentive drug delivery system for controlled drug release in the stomach and into the upper intestines. U.S. Patent Application 13/676,241, filed November 28, 2013.
[4]
Kumar, V.; Shavej, A.; Romi, B.S. Gastroretentive Dosage System And Process Of Preparation Thereof. U.S. Patent Application 14/350,615, filed September 18, 2014.
[5]
Berner, B.; Jenny, L.H.; John, W. Gastric retentive oral dosage form with restricted drug release in the lower gastrointestinal tract. U.S. Patent 7,976,870, filed July 12, 2011.
[6]
Friedman, M.; David, K. Novel Gastroretentive Delivery System. U.S. Patent Application 13/121,546, filed November 3, 2011.
[7]
Kavimandan, N.J.; Lakshman, J.P.; Matharu, A.S.; Ogorka, J.; Royce, A.E.; Teelucksingh, N.R. Inventors; Novartis AG, assignee.Extended release gastro-retentive oral drug delivery system for Valsartan. United States Patent Application: US 12/377,949. 2010, filed September 16, 2010.
[8]
Verma, A.; Dubey, J.; Verma, N.; Nayak, A.K. Chitosan hydroxypropyl methylcellulose matrices as carriers for hydrodynamically balanced capsules of Moxifloxacin HCl. Curr. Drug Deliv., 2017, 14(1), 83-90.
[http://dx.doi.org/10.2174/1567201813666160504100842] [PMID: 27142106]
[9]
Gennaro, A.R.; Chase, G.D.; Marderosian, A.D. Remington’s Pharmaceutical Sciences; Mack Publishing Co: Easton. PA,. , 1999, 50, pp. 948-965.
[10]
Nayak, A.K. Controlled release drug delivery systems. Sci. J. UBU, 2001, 2, 1-8.
[11]
Malakar, J.; Nayak, A.K. Theophylline release behavior from hard gelatin capsules containing hydrophilic polymeric matrices. J. Pharm. Educ. Res., 2012, 3(1), 1-8.
[12]
Mao, H.Q.; Roy, K.; Troung-Le, V.L.; Janes, K.A.; Lin, K.Y.; Wang, Y.; August, J.T.; Leong, K.W. Chitosan-DNA nanoparticles as gene carriers: synthesis, characterization and transfection efficiency. J. Control. Release, 2001, 70(3), 399-421.
[http://dx.doi.org/10.1016/S0168-3659(00)00361-8] [PMID: 11182210]
[13]
Kumar, M.N.V.R.; Muzzarelli, R.A.; Muzzarelli, C.; Sashiwa, H.; Domb, A.J. Chitosan chemistry and pharmaceutical perspectives. Chem. Rev., 2004, 104(12), 6017-6084.
[http://dx.doi.org/10.1021/cr030441b] [PMID: 15584695]
[14]
Abedini, F.; Mohammad, E. Abbas, Hemmati R.; Abraham, JD.; Hossein, H. Overview on natural hydrophilic polysaccharide polymers in drug delivery. Polym. Adv. Technol., 2018, 29(10), 2564-2573.
[http://dx.doi.org/10.1002/pat.4375]
[15]
Dubey, J.; Verma, A.; Verma, N. Evaluation of chitosan based polymeric matrices for sustained stomach specific delivery of propranolol hydrochloride. Indian Journal of Materials Science, 2015, 1-10.
[http://dx.doi.org/10.1155/2015/312934]
[16]
Siepmann, J.; Kranz, H.; Bodmeier, R.; Peppas, N.A. HPMC-matrices for controlled drug delivery: a new model combining diffusion, swelling, and dissolution mechanisms and predicting the release kinetics. Pharm. Res., 1999, 16(11), 1748-1756.
[http://dx.doi.org/10.1023/A:1018914301328] [PMID: 10571282]
[17]
Siepmann, J.; Peppas, N.A. Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC). Adv. Drug Deliv. Rev., 2012, 64, 163-174.
[http://dx.doi.org/10.1016/j.addr.2012.09.028] [PMID: 11369079]
[18]
Soni, S.; Ram, V.; Verma, A. Crushed puffed rice-HPMC-chitosan based single-unit hydrodynamically balanced system for the sustained stomach specific delivery of metoprolol succinate. J. Appl. Pharm., 2017, 7(12), 047-057.
[http://dx.doi.org/10.7324/JAPS.2017.71206]
[19]
US Pharmacopoeia National Formulary, USP 23/NF 18; United States Pharmacopoeia Convention Inc.: Rockville, MD, 2000.
[20]
Soni, S.; Verma, A.; Ram, V. Evaluation of chitosan-hydroxy propyl methyl cellulose as a single unit hydrodynamically balanced sustained release matrices for stomach specific delivery of Piroxicam. MOJ Bioequiv Availab, 2016, 1(3), 00014.
[http://dx.doi.org/10.15406/mojbb.2015.01.00014]
[21]
Verma, A.; Bansal, A.K.; Ghosh, A.; Pandit, J.K. Low molecular mass chitosan as carrier for a hydrodynamically balanced system for sustained delivery of ciprofloxacin hydrochloride. Acta Pharm., 2012, 62(2), 237-250.
[http://dx.doi.org/10.2478/v10007-012-0013-2] [PMID: 22750821]
[22]
Soni, S.; Verma, N.; Verma, A.; Pandit, J.K. Gelucire based floating emulsion gel beads: a potential carrier for sustained stomach specific drug delivery. Farmacia, 2017, 65(1), 142-152.
[23]
Ganjoo, R.; Soni, S.; Ram, V. Effect of release modifier on hydrodynamically balanced system of Ketoprofen for sustained delivery system. Inventi Rapid: NDDS, 2013, 4, 283-288.
[24]
Kumar, L.; Sreenivasa Reddy, M.; Managuli, R.S.; Pai, K. G. Full factorial design for optimization, development and validation of HPLC method to determine valsartan in nanoparticles. Saudi Pharm. J., 2015, 23(5), 549-555.
[http://dx.doi.org/10.1016/j.jsps.2015.02.001] [PMID: 26594122]
[25]
Durbin, J.; Watson, G.S. Testing for serial correlation in least squares regression. I. Biometrika, 1950, 37(3-4), 409-428.
[http://dx.doi.org/10.1093/biomet/37.3-4.409] [PMID: 14801065]
[26]
Baumgartner, S.; Kristl, J.; Peppas, N.A. Network structure of cellulose ethers used in pharmaceutical applications during swelling and at equilibrium. Pharm. Res., 2002, 19(8), 1084-1090.
[http://dx.doi.org/10.1023/A:1019891105250] [PMID: 12240932]
[27]
Colombo, P.; Bettini, R.; Santi, P.; Peppas, N.A. Swellable matrices for controlled drug delivery: gel-layer behaviour, mechanisms and optimal performance. Pharm. Sci. Technol. Today, 2000, 3(6), 198-204.
[http://dx.doi.org/10.1016/S1461-5347(00)00269-8] [PMID: 10840390]
[28]
Hamdani, J.; Moës, A.J.; Amighi, K. Development and in vitro evaluation of a novel floating multiple unit dosage form obtained by melt pelletization. Int. J. Pharm., 2006, 322(1-2), 96-103.
[http://dx.doi.org/10.1016/j.ijpharm.2006.05.052] [PMID: 16824707]
[29]
Rastogi, V.; Kumar, A.; Yadav, P.; Hegde, R.; Rastogi, P. Mathematical optimization and investigation on polymeric blend of Chitosan and Hydroxypropyl Methylcellulose K4M for sustained release of Metronidazole. Asian Journal of Pharmaceutics, 2016, 9(6), S1-S10.
[30]
Hejazi, R.; Amiji, M. Chitosan-based gastrointestinal delivery systems. J. Control. Release, 2003, 89(2), 151-165.
[http://dx.doi.org/10.1016/S0168-3659(03)00126-3] [PMID: 12711440]
[31]
Jang, M.K.; Nah, J.W. Characterization and modification of low molecular water-soluble chitosan for pharmaceutical application. Bull. Korean Chem. Soc., 2003, 24(9), 1303-1307.
[http://dx.doi.org/10.5012/bkcs.2003.24.9.1303]
[32]
Patel, S.; Patel, M.; Patel, N.G.; Patel, R.K. Pharmaceutical significance of Chitosan: A review. Pharm. Rev., 2006, 1(6), 10-19.
[33]
Fukuda, M.; Peppas, N.A.; McGinity, J.W. Properties of sustained release hot-melt extruded tablets containing chitosan and xanthan gum. Int. J. Pharm., 2006, 310(1-2), 90-100.
[http://dx.doi.org/10.1016/j.ijpharm.2005.11.042] [PMID: 16413153]


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Article Details

VOLUME: 10
ISSUE: 3
Year: 2020
Published on: 10 September, 2020
Page: [237 - 249]
Pages: 13
DOI: 10.2174/2210303110999200408122629
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