Preparation of Liquid Oral Mucoadhesive Gastro-retentive System of Nimodipine

Author(s): Mai Mamdouh, Ahmed Donia, Ebtessam Essa*, Gamal El Maghraby.

Journal Name: Current Drug Delivery

Volume 16 , Issue 9 , 2019

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Graphical Abstract:


Background: Nimodipine is a calcium channel blocker frequently used in critical care settings. It is mainly absorbed in the upper gastrointestinal tract. Accordingly, the development of gastroretentive formulation will be beneficial. The benefit would be maximized for critical care patients if the developed system was in liquid form to facilitate the administration through nasogastric tubing.

Objective: Development of gastro-retentive liquid oral controlled release formulation of nimodipine through in situ gellation.

Methods: Nimodipine dissolution was improved by solid dispersion (SD) using poloxamer 407. Sodium alginate solutions (1, 1.5 and 2%w/v) were loaded with the optimized SD microparticles. Carboxymethylcellulose was added to modulate the release and to augment mucoadhesion power. All in situ gelling alginate solutions were characterized regarding viscosity, gelling capacity and drug release. SD microparticles showed considerable improvement in nimodipine dissolution.

Results: All alginate systems were pourable. Increasing alginate concentration increased the gelling capacity and reduced drug release rate. The addition of carboxymethylcellulose produced greater control over drug release rate. X-ray radiography showed successful stomach-retention over 8 hours in rabbits, which correlates with the controlled release pattern of the developed systems.

Conclusion: The study provides the formulator with a range of gastroretentive controlled release formulations of nimodipine while maintaining the convenience of administration through nasogastric tubing with the potential for enhanced bioavailability.

Keywords: Nimodipine, in situ gelling, gastroretentive, mucoadhesion, nasogastric tube feeding, sodium alginate.

Rao, N.G.; Subhan, M. Development of nimodipine fast dissolving tablets: Effect of functionality of hydrophilic carriers on solid dispersion technique. J. Pharm. Biomed. Sci., 2010, 8(10), 1-7.
FDA Drug Safety Communication. Serious medication errors from intravenous administration of nimodipine oral capsules; US food and drug administration, 2010.
Jeffrey, S. FDA Nod for nymalize nimodipine oral solution in SAH Medscape, 2013.
Patil, A.; Majahar, S.; Irfani, G. Floating tablets of Nimodipine and its inclusion complex with β-Cyclodextrin for controlled release. Int. J. Pharm. Tech. Res., 2011, 3, 619-625.
Mandal, U.K.; Chatterjee, B.; Senjoti, F.G. Gastro-retentive drug delivery systems and their in vivo success A.J.P.S. A recent update, 2016, 11, 575-584.
Zahir-Jouzdani, F.; Wolf, J.D.; Atyabi, F.; Bernkop-Schnürch, A. In situ gelling and mucoadhesive polymers: Why do they need each other? Expert Opin. Drug Deliv., 2018, 15(10), 1007-1019.
[] [PMID: 30173567]
Nirmal, H.B.; Bakiwal, S.R.; Pawar, S.P. In situ gel: New trend in controlled and sustained drug delivery system. Int. J. Pharm. Tech. Res., 2010, 2, 1398-1408.
Kubo, W.; Miyazaki, S.; Attwood, D. Oral sustained delivery of paracetamol from in situ-gelling gellan and sodium alginate formulations. Int. J. Pharm., 2003, 258(1-2), 55-64.
[] [PMID: 12753753]
Madan, M.; Bajaj, A.; Lewis, S.; Udupa, N.; Baig, J.A. In situ forming polymeric drug delivery systems. Indian J. Pharm. Sci., 2009, 71(3), 242-251.
[] [PMID: 20490289]
El Maghraby, G.M.; Elzayat, E.M.; Alanazi, F.K. Development of modified in situ gelling oral liquid sustained release formulation of dextromethorphan. Drug Dev. Ind. Pharm., 2012, 38(8), 971-978.
[] [PMID: 22092113]
Atuma, C.; Strugala, V.; Allen, A.; Holm, L. The adherent gastrointestinal mucus gel layer: thickness and physical state in vivo. Am. J. Physiol. Gastrointest. Liver Physiol., 2001, 280(5), G922-G929.
[] [PMID: 11292601]
Parhizkar, E.; Emadi, L.; Alipour, S. Development and evaluation of midazolam in situ nasal gel properties in presence of solubility enhancers at cilia-friendly pH. Macromol. Res., 2017, 25, 255-261.
krediel, R.N.; Duque, M.D.; Serra, C.H.R.; Velasco, M.V.R.; Baby, A. R.; Kaneko, T. M.; Consiglieri, V.O. Dissolution enhancement and characterization of nimodipine solid dispersions with poloxamer 407or PEG 6000. J. Dispers. Sci. Technol., 2012, 33, 1354-1359.
El Maghraby, G.M.; Elsisi, A.E.; Elmeshad, G.A. Development of liquid oral sustained release formulations of nateglinide: In vitro and in vivo evaluation. Drug Deliv. Sci. Tech, 2015, 29, 70-77.
El Maghraby, G.M.; Elzayat, E.M.; Alanazi, F.K. Investigation of in situ gelling alginate formulations as a sustained release vehicle for co-precipitates of dextromethrophan and Eudragit S 100. Acta Pharm., 2014, 64(1), 29-44.
[] [PMID: 24670350]
Miyazaki, S.; Kubo, W.; Attwood, D. Oral sustained delivery of theophylline using in-situ gelation of sodium alginate. J. Control. Release, 2000, 67(2-3), 275-280.
[] [PMID: 10825560]
Nafee, N.A.; Boraie, M.A.; Ismail, F.A.; Mortada, L.M. Design and characterization of mucoadhesive buccal patches containing cetylpyridinium chloride. Acta Pharm., 2003, 53(3), 199-212.
[PMID: 14769243]
Mahrous, G.M. Formulation and evaluation of buccoadhesive discks of benzocaine. World J. Pharm. Res., 2015, 4, 141-154.
El-Maghraby, G.M.; Abdelzaher, M.M. Formulation and evaluation of simvastatin buccal film Formulation and evaluation of simvastatin buccal film J. Appl. Pharm. Sci, 2015, 5, 070-077.
Alanazi, F.K.; Abdel Rahman, A.A.; Mahrous, G.M.; Alsarra, I.A. Formulation and physicochemical characterization of buccoadhesive films containing ketorolac. J. Drug Deliv. Sci. Technol., 2007, 17, 183-192.
Habib, F.; Abdel Azeem, M.; Fetih, G.; Safwat, M. Mucoadhesive buccal patches of lornoxicam. Bull. Pharm. Sci., 2010, 33, 59-68.
Kajale, A.D.; Chandewar, A.V. Formulation development and evaluation of oral floating in situ gel of Ilaprazole. Pharm. Sin., 2016, 7, 51-63.
Ghareeb, M.M.; Neamah, A.J. Formulation and Characterization of nimodipine nanoemulsion as ampoule for oral route. Int. J. Pharm. Sci. Res., 2017, 8, 591-602.
Parmar, R.B.; Baria, A.H.; Tank, H.M.; Faldu, S.D. Formulation and evaluation of domperidone fast dissolvingtablets. Int. J. Pharm. Tech. Res., 2009, 1, 483-487.
Essa, E.; Negm, M.; Zin Eldin, E.; El Maghraby, G.M. G.M. Fast disintegrating tablets of amiodarone for intra-oral administration J. App. Pharm. Sci, 2017, 7, 064-072.
Zhao, Y.; Xin, T.; Ye, T.; Yang, X.; Pan, W. Solid dispersion in the development of a nimodipine delayed-release tablet formulation. Asian J. Pharm Sci., 2014, 9, 35-44.
Essa, E.A.; Balata, G.F. Preparation and characterization of domperidone solid dispersions. Pak. J. Pharm. Sci., 2012, 25(4), 783-791.
[PMID: 23009995]
Teng, Z.; Yu, M.; Ding, Y.; Zhang, H.; Shen, Y.; Jiang, M.; Liu, P.; Opoku-Damoah, Y.; Webster, T.J.; Zhou, J. Preparation and characterization of nimodipine-loaded nanostructured lipid systems for enhanced solubility and bioavailability. Int. J. Nanomedicine, 2018, 14(14), 119-133.
[] [PMID: 30613141]
Park, C.W.; Tung, N.T.; Rhee, Y.S.; Kim, J.Y.; Oh, T.O.; Ha, J.M.; Chi, S.C.; Park, E.S. Physicochemical, pharmacokinetic and pharmacodynamic evaluations of novel ternary solid dispersion of rebamipide with poloxamer 407. Drug Dev. Ind. Pharm., 2013, 39(6), 836-844.
[] [PMID: 22510064]
Essa, E.A.; Diwakat, M. Enhancement of simvastatin dissolution via surface solid dispersion; Effect of carriers and wetting agents J. App. Pharm. Sci, 2015, 5, 053-054.
Khan, K.A. The concept of dissolution efficiency. J. Pharm. Pharmacol., 1975, 27(1), 48-49.
[] [PMID: 235616]
Taylor, M.J.; Tomlins, P.; Sahota, T.S. Thermoresponsive Gels. Gels, 2017, 3(1), 4-11.
[] [PMID: 30920501]
Kajale, A.D.; Chandewar, A.V. Formulation and evaluation of oral floating In situ gel of Tramadol hydrochloride. Pharm. Chem. J., 2016, 3, 267-279.
Bernkop-Schnürch, A. Mucoadhesive polymers: Strategies, achievements and future challenges. Adv. Drug Deliv. Rev., 2005, 57(11), 1553-1555.
[] [PMID: 16181704]

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Article Details

Year: 2019
Page: [862 - 871]
Pages: 10
DOI: 10.2174/1567201816666191014102531
Price: $65

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