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The International Journal of Gastroenterology and Hepatology Diseases

Author(s): Onyishi Ikechuchukwu Virgilus, Chime Salome Amarachi*, Ike-Onyishi Ugochi Elizabeth, Ndukauba Ijeoma, Akpa Paul Achile*, Ezeudoh Clara Chigozie and Ogbonna Emmanuella Tochuchukwu

DOI: 10.2174/0126662906296242240603104029

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Development and In vitro Evaluation of Pantoprazole-Sustained Release Effervescent Floating Tablets for Effective Management of Ulcer

Article ID: e250624231309 Pages: 9

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Abstract

Introduction: Pantoprazole is a very suitable drug for the treatment of numerous acid-related conditions in humans and mammals. Owing to its short half-life (0.9 - 1.9 h), it is ideal for sustained release formulation.

Methods: This study was aimed at developing pantoprazole gastroretentive (GR) controlledrelease tablets and to determine the effects of this formulation and processing parameters on drug release and other critical quality attributes of directly compressed tablets produced using different matrix-forming polymers, namely, Hydroxypropyl methylcellulose (HPMC), chitosan, sodium alginate, maize starch, kappa- carrageenan, and propyl vinyl pyrrolidine PVP K- 30 when formulated into effervescent Floating Drug Delivery Systems (FDDS).

Results: The buoyancy lag time of less than 5 seconds and a total floating time of more than 12 hours for all batches is a good indication of achieved floatation for FDDS.

Conclusion: Validation processes initiated with the five batches indicated that the polymer blends had the potential for the formulation of pantoprazole FDDS and, hence, could enhance patient compliance and better treatment outcomes due to their sustained release potentials.

Keywords: Buoyancy lag time, controlled release tablets, gastro-retentive drug delivery- effervescence tablets, floating tablets, k-carrageenan, ulcer, proton pump inhibitors, pantoprazole.

[1]
NHSinform. Stomach ulcers. Available From https://www.nhsinform.scot/illnesses-and-conditions/stomach-liver-and-gastrointestinal-tract/stomach-ulcer/ (Accessed on 8th November, 2023.)
[2]
Sverdén E, Agréus L, Dunn JM, Lagergren J. Peptic ulcer disease. BMJ 2019; 367: l5495.
[http://dx.doi.org/10.1136/bmj.l5495] [PMID: 31578179]
[3]
Lanas A, Chan FKL. Peptic ulcer disease. Lancet 2017; 390(10094): 613-24.
[http://dx.doi.org/10.1016/S0140-6736(16)32404-7] [PMID: 28242110]
[4]
Xie X, Ren K, Zhou Z, Dang C, Zhang H. The global, regional and national burden of peptic ulcer disease from 1990 to 2019: A population-based study. BMC Gastroenterol 2022; 22(1): 58.
[http://dx.doi.org/10.1186/s12876-022-02130-2] [PMID: 35144540]
[5]
Rosenstock SJ, Jørgensen T. Prevalence and incidence of peptic ulcer disease in a Danish County--a prospective cohort study. Gut 1995; 36(6): 819-24.
[http://dx.doi.org/10.1136/gut.36.6.819] [PMID: 7615266]
[6]
Gralnek I, Dumonceau JM, Kuipers E, et al. Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2015; 47(10): a1-a46.
[http://dx.doi.org/10.1055/s-0034-1393172] [PMID: 26417980]
[7]
Dall M, Schaffalitzky de Muckadell OB, Lassen AT, Hallas J. There is an association between selective serotonin reuptake inhibitor use and uncomplicated peptic ulcers: A population‐based case-control study. Aliment Pharmacol Ther 2010; 32(11-12): 1383-91.
[http://dx.doi.org/10.1111/j.1365-2036.2010.04472.x] [PMID: 21050241]
[8]
Krag M, Perner A, Wetterslev J, et al. Prevalence and outcome of gastrointestinal bleeding and use of acid suppressants in acutely ill adult intensive care patients. Intensive Care Med 2015; 41(5): 833-45.
[http://dx.doi.org/10.1007/s00134-015-3725-1] [PMID: 25860444]
[9]
Lau JY, Sung J, Hill C, Henderson C, Howden CW, Metz DC. Systematic review of the epidemiology of complicated peptic ulcer disease: Incidence, recurrence, risk factors and mortality. Digestion 2011; 84(2): 102-13.
[http://dx.doi.org/10.1159/000323958] [PMID: 21494041]
[10]
Jungnickel PW. A new proton pump inhibitor, in new drugs. Clin Ther 2000; 22(11): 1268-93.
[11]
Welage LS, Berardi RR. Evaluation of omeprazole, lansoprazole, pantoprazole, and rabeprazole in the treatment of acidrelated diseases. J Am Pharm Assoc 2000; 40(1): 4052-62.
[12]
Richardson P, Hawkey CJ, Stack WA. Proton pump inhibitors. Pharmacology and rationale for use in gastrointestinal disorders. Drugs 1998; 56(3): 307-35.
[http://dx.doi.org/10.2165/00003495-199856030-00002] [PMID: 9777309]
[13]
Pallotta S, Pace F, Marelli S. Rabeprazole: A second-generation proton pump inhibitor in the treatment of acid-related disease. Expert Rev Gastroenterol Hepatol 2008; 2(4): 509-22.
[http://dx.doi.org/10.1586/17474124.2.4.509] [PMID: 19072398]
[14]
Tytgat GN. Shortcomings of the first-generation proton pump inhibitors. Eur J Gastroenterol Hepatol 2001; 13 (Suppl. 1): S29-33.
[PMID: 11430506]
[15]
Kromer W. Similarities and differences in the properties of substituted benzimidazoles: A comparison between pantoprazole and related compounds. Digestion 1995; 56(6): 443-54.
[http://dx.doi.org/10.1159/000201275] [PMID: 8536813]
[16]
Ankalu D, Nandhakumar S, Devalarao G. Delayed release formulation of pantoprazole using sureteric aqueous dispersion system. Pharm Lett 2013; 5(5): 175-86.
[17]
Shin JM, Besancon M, Prinz C. Continuing development of acid pump inhibitors: Site of action of pantoprazole. Aliment Pharmacol Ther 1994; 8 (Suppl. 1): 11-23.
[18]
Sachs G. Proton pump inhibitors and acid-related diseases. Pharmacotherapy 1997; 17(1): 22-37.
[http://dx.doi.org/10.1002/j.1875-9114.1997.tb03675.x] [PMID: 9017763]
[19]
Sachs G, Prinz C, Loo D, Bamberg K, Besancon M, Shin JM. Gastric acid secretion: Activation and inhibition. Yale J Biol Med 1994; 67(3-4): 81-95.
[PMID: 7502535]
[20]
Fitton A, Wiseman L. Pantoprazole. Drugs 1996; 51(3): 460-82.
[http://dx.doi.org/10.2165/00003495-199651030-00012] [PMID: 8882382]
[21]
Huber R, Kohl B, Sachs G. Review article: The continuing development of proton pump inhibitors with particular reference to pantoprazole. Aliment Pharmaco1 Ther 1995; 9: 363-78.
[22]
Simon B, Müller P, Bliesath H, et al. Single intravenous administration of the H +, K + ‐ATPase inhibitor BY 1023/SK&F 96022—inhibition of pentagastrin‐stimulated gastric acid secretion and pharmacokinetics in man. Aliment Pharmacol Ther 1990; 4(3): 239-45.
[http://dx.doi.org/10.1111/j.1365-2036.1990.tb00468.x] [PMID: 1966542]
[23]
Simon B, Muller P, Hartmann M. Pentagastrin- stimulated gastric acid secretion and pharmacokinetics following single and repeated intravenous administration of the gastric H+,K+-ATPase-inhibitor pantoprazole (BY 1023/SK&F%O22) in healthy vohmteets. Z Gastroenterol 1990; 28(9): 443-7.
[24]
Hannan A, Weil J, Broom C, Walt RP. Effects of oral pantoprazole on 24‐hour intragastric acidity and plasma gastrin profiles. Aliment Pharmacol Ther 1992; 6(3): 373-80.
[http://dx.doi.org/10.1111/j.1365-2036.1992.tb00058.x] [PMID: 1600053]
[25]
Koop H, Kuly S, Flüg M, et al. Intragastric pH and serum gastrin during administration of different doses of pantoprazole in healthy subjects. Eur J Gastroenterol Hepatol 1996; 8(9): 915-8.
[PMID: 8889461]
[26]
Mössner J, Hölscher AH, Herz R, Schneider A. A double‐blind study of pantoprazole and omeprazole in the treatment of reflux oesophagitis: A multicentre trial. Aliment Pharmacol Ther 1995; 9(3): 321-6.
[http://dx.doi.org/10.1111/j.1365-2036.1995.tb00388.x] [PMID: 7654895]
[27]
Escourrou J, Deprez P, Saggioro A, Geldof H, Fischer R, Maier C. Maintenance therapy with pantoprazole 20 mg prevents relapse of reflux oesophagitis. Aliment Pharmacol Ther 1999; 13(11): 1481-91.
[http://dx.doi.org/10.1046/j.1365-2036.1999.00651.x] [PMID: 10571605]
[28]
Andersson T. Pharmacokinetics, metabolism and interactions of acid pump inhibitors. Focus on omeprazole, lansoprazole and pantoprazole. Clin Pharmacokinet 1996; 31(1): 9-28.
[http://dx.doi.org/10.2165/00003088-199631010-00002] [PMID: 8827397]
[29]
Huber R, Hartmann M, Bliesath H, Lühmann R, Steinijans VW, Zech K. Pharmacokinetics of pantoprazole in man. Int J Clin Pharmacol Ther 1996; 34(5): 185-94.
[PMID: 8738854]
[30]
Tanaka M, Yamazaki H, Ryokawa Y, Hakusui H, Nakamichi N, Sekino H. Pharmacokinetics and tolerance of pantoprazole, a proton pump inhibitor after single and multiple oral doses in healthy Japanese volunteers. Int J Clin Pharmacol Ther 1996; 34(10): 415-9.
[PMID: 8897077]
[31]
Pue MA, Laroche J, Meineke I, de Mey C. Pharmacokinetics of pantoprazole following single intravenous and oral administration to healthy male subjects. Eur J Clin Pharmacol 1993; 44(6): 575-8.
[http://dx.doi.org/10.1007/BF02440862] [PMID: 8405016]
[32]
Witzel L, Gütz H, Hüttemann W, Schepp W. Pantoprazole versus omeprazole in the treatment of acute gastric ulcers. Aliment Pharmacol Ther 1995; 9(1): 19-24.
[http://dx.doi.org/10.1111/j.1365-2036.1995.tb00346.x] [PMID: 7766739]
[33]
Hotz J, Plein K, Schonekas H, Rose K. Pantoprazole is superior to ranitidine in the treatment of acute gastric ulcer. Stand J Gastroenterol 1995; 30: 111-5.
[34]
Patel SS, Ray S, Thakur RS. Formualtion and evaluation of floating drug delivery system containing clarithromycin for Helicobacter pylori. Acta Pol Pharm 2006; 63(1): 53-61.
[35]
Garg S, Sharma S. Business Briefing Pharmatech 2003; 160: 66.
[36]
Mayavanshi AV, Gajjar SS. Floating drug delivery systems to increase gastric retention of drugs: A Review. Research J Pharm and Tech 2008; 1(4): 345-8.
[37]
Londhe S, Gattani S, Surana S. Development of floating drug delivery system with biphasic release for verapamil hydrochloride: In vitro and in vivo evaluation. J Pharm Sci Technol 2010; 2(11): 361-7.
[38]
Hoffman A, Stepensky D, Lavy E, Eyal S, Klausner E, Friedman M. Pharmacokinetic and pharmacodynamic aspects of gastroretentive dosage forms. Int J Pharm 2004; 277(1-2): 141-53.
[http://dx.doi.org/10.1016/j.ijpharm.2003.09.047] [PMID: 15158977]
[39]
Talukder R, Fassihi R. Gastroretentive delivery systems: A mini review. Drug Dev Ind Pharm 2004; 30(10): 1019-28.
[http://dx.doi.org/10.1081/DDC-200040239] [PMID: 15595568]
[40]
Jaimini M, Rana A, Tanwar Y. Formulation and evaluation of famotidine floating tablets. Curr Drug Deliv 2007; 4(1): 51-5.
[http://dx.doi.org/10.2174/156720107779314730] [PMID: 17269917]
[41]
Ali J, Arora S, Ahuja A, et al. Formulation and development of hydrodynamically balanced system for metformin: in vitro and in vivo evaluation. Eur J Pharm Biopharm 2007; 67(1): 196-201.
[http://dx.doi.org/10.1016/j.ejpb.2006.12.015] [PMID: 17270409]
[42]
Varshosaz J, Tavakoli N, Roozbahani F. Formulation and in vitro characterization of ciprofloxacin floating and bioadhesive extended-release tablets. Drug Deliv 2006; 13(4): 277-85.
[http://dx.doi.org/10.1080/10717540500395106] [PMID: 16766469]
[43]
Maggi L, Machiste EO, Torre ML, Conte U. Formulation of biphasic release tablets containing slightly soluble drugs. Eur J Pharm Biopharm 1999; 48(1): 37-42.
[http://dx.doi.org/10.1016/S0939-6411(99)00019-3] [PMID: 10477326]
[44]
Singh B, Kim KH. Floating drug delivery systems: An approach to oral controlled drug delivery via gastric retention. J Control Release 2000; 63(3): 235-59.
[http://dx.doi.org/10.1016/S0168-3659(99)00204-7] [PMID: 10601721]
[45]
Kim CJ. Dosage Form Design. Lancaster: Technomic Pub 2000.
[46]
Chime SA, Kenechukwu FC, Onunkwo GC, Attama AA, Ogbonna JD. Micromeritic and antinociceptive properties of lyophilized indomethacin loaded SLMs based on solidified reverse micellar solutions. J Pharm Res 2012; 5(6): 3410-6.
[47]
Chime S, Umeyor EC, Onyishi VI, Onunkwo GC, Attama AA. Analgesic and micromeritic evaluations of SRMS-based oral lipospheres of diclofenac potassium. Indian J Pharm Sci 2013; 75(3): 302-9.
[http://dx.doi.org/10.4103/0250-474X.117436] [PMID: 24082346]
[48]
Onyishi IV, Chime SA, Egwu E. Application of ĸ-carrageenan as a sustained release matrix in floating tablets containing sodium salicylate. Afr J Pharm Pharmacol 2013; 7(39): 2667-73.
[49]
Higuchi T. Rate of release of medicaments from ointment bases containing drugs in suspension. J Pharm Sci 1961; 50(10): 874-5.
[http://dx.doi.org/10.1002/jps.2600501018] [PMID: 13907269]
[50]
Higuchi T. Mechanism of sustained‐action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci 1963; 52(12): 1145-9.
[http://dx.doi.org/10.1002/jps.2600521210] [PMID: 14088963]
[51]
Chime SA, Onunkwo GC, Onyishi IV. Kinetics and mechanisms of drug release from swellable and non-swellable matrices: A review. Res J Pharm Biol Chem Sci 2013; 4(2): 97-103.
[52]
Ritger PL, Peppas NA. A simple equation for description of solute release I. Fickian and non-fickian release from non-swellable devices in the form of slabs, spheres, cylinders or discs. J Control Release 1987; 5(1): 23-36.
[http://dx.doi.org/10.1016/0168-3659(87)90034-4]
[53]
Shah RB, Tawakkul MA, Khan MA. Comparative evaluation of flow for pharmaceutical powders and granules. AAPS PharmSciTech 2008; 9(1): 250-8.
[http://dx.doi.org/10.1208/s12249-008-9046-8] [PMID: 18446489]
[54]
Carr RL. Evaluating flow properties of solids. Chem Eng 1965; 72: 69-72.
[55]
Chime SA, Okeke JK. Comparative evaluation of Prosopis africana seed gum as a sustained release binder in colon targeted diclofenac potassium floating tablets. J Curr Pharma Res 2015; 5(2): 1411-24.
[http://dx.doi.org/10.33786/JCPR.2015.v05i02.005]
[56]
Chime SA, Obitte NC, Onyish VI, Nwosu IE. Development of cross-linked alginate beads by ionotropic gelation technique for controlled release of diclofenac sodium. Am J Pharm Tech Res 2013; 3(5): 428-37.
[57]
Desai D, Kothari S, Huang M. Solid-state interaction of stearic acid with povidone and its effect on dissolution stability of capsules. Int J Pharm 2008; 354(1-2): 77-81.
[http://dx.doi.org/10.1016/j.ijpharm.2007.11.042] [PMID: 18194844]
[58]
Sammour OA, Hammad MA, Megrab NA, Zidan AS. Formulation and optimization of mouth dissolve tablets containing rofecoxib solid dispersion. AAPS PharmSciTech 2006; 7(2): E167-75.
[http://dx.doi.org/10.1208/pt070255] [PMID: 16796372]
[59]
Chime SA, Akpa PA, Ugwuanyi CC, Attama AA. Anti-inflammatory and gastroprotective properties of aspirin - Entrapped solid lipid microparticles. Recent Pat Inflamm Allergy Drug Discov 2020; 14(1): 78-88.
[http://dx.doi.org/10.2174/1872213X14666200108101548] [PMID: 31912772]
[60]
Thakkar VT, Shah PA, Soni TG, Parmar MY, Gohel MC, Gandhi TR. Goodness-of-fit model-dependent approach for release kinetics of levofloxacin hemihydrates floating tablet. Dissolut Technol 2009; 16(1): 35-9.
[http://dx.doi.org/10.14227/DT160109P35]
[61]
Attama AA, Nkemnele MO. In vitro evaluation of drug release from self micro-emulsifying drug delivery systems using a biodegradable homolipid from Capra hircus. Int J Pharm 2005; 304(1-2): 4-10.
[http://dx.doi.org/10.1016/j.ijpharm.2005.08.018] [PMID: 16198521]
[62]
Chime S, Ugwu CE, Ejiofor EU, Onunkwo GC. Application of Cyperus esculentus oil in the development of sustained release diclofenac sodium-loaded nanostructured lipid carrier. Journal of Current Biomedical Research 2022; 2(3, May-June): 145-59.
[http://dx.doi.org/10.54117/jcbr.v2i3.23]
[63]
Gugu TH, Chime SA, Attama AA. Solid lipid microparticles: An approach for improving oral bioavailability of aspirin. As. J Pharm Sci 2015; 10(5): 425-32.
[64]
Chime SA, Attama AA, Onunkwo GC. Assessment of the anti-malarial properties of dihydroartemisinin- piperaquine phosphate solid lipid-based tablets. Recent Adv Antiinfect Drug Discov 2022; 17(3): 103-17.
[65]
Momoh AM, Chime SA, Anih CV, et al. A novel formulation design based on hetero-templated solid lipid microparticles to improve the solubility of anti-inflammatory piroxicam for oral administration. New J Chem 2022; 2022(46): 3961-5.
[66]
Nnamani PO, Ogbonna CC, Dibua EU, Ezedigboh NN, Attama AA. Sustained circulation time of glibenclamide from pegylated solid lipid microparticles. Int J Novel Drug Deliv Tech 2012; 2(2): 283-90.
[67]
Umeyor EC, Kenechukwu FC, Ogbonna JD, Chime SA, Attama A. Preparation of novel solid lipid microparticles loaded with gentamicin and its evaluation in vitro and in vivo. J Microencapsul 2012; 29(3): 296-307.
[http://dx.doi.org/10.3109/02652048.2011.651495] [PMID: 22283701]
[68]
Momoh MA, Akpa PA. Attama, AA Phospholipon 90G based SLMs loaded with ibuprofen: An oral antiinflammatory and gastro intestinal sparing evaluation in rats. Pak J Zool 1657; 44(6): 1657-64.
[69]
Chinaeke EE, Chime SA, Onyishi IV, Attama AA, Okore VC. Formu lation development and evaluation of the anti-malaria properties of sustained release artesunate-loaded solid lipid microparticles based on phytolipids. Drug Deliv 2014; 20(5): 546-54.
[PMID: 24479677]
[70]
Chinaeke EE, Chime SA, Kenechukwu FC, Müller-Goymann CC, Attama AA, Okore VC. Formulation of novel artesunate-loaded Solid Lipid Microparticles (SLMs) based on dika wax matrices: in vitro and in vivo evaluation. J Drug Deliv Sci Technol 2014; 24(1): 69-77.
[http://dx.doi.org/10.1016/S1773-2247(14)50010-X]
[71]
Attama AA, Okafor CE, Builders PF, Okorie O. Formulation and in vitro evaluation of a PEGylated microscopic lipospheres delivery system for ceftriaxone sodium. Drug Deliv 2009; 16(8): 448-57.
[http://dx.doi.org/10.3109/10717540903334959] [PMID: 19839789]
[72]
Chime SA, Attama AA, Builders PF, Onunkwo GC. Sustained-release diclofenac potassium-loaded solid lipid microparticle based on solidified reverse micellar solution: in vitro and in vivo evaluation. J Microencapsul 2013; 30(4): 335-45.
[http://dx.doi.org/10.3109/02652048.2012.726284] [PMID: 23057661]
[73]
Chinaeke EE, Chime SA, Ogbonna JDN, Attama AA, Müller-Goymann CC, Okore VC. Evaluation of dika wax-soybean oil-based artesunate-loaded lipospheres: In vitro-in vivo correlation studies. J Microencapsul 2014; 31(8): 796-804.
[http://dx.doi.org/10.3109/02652048.2014.940008] [PMID: 25090593]
[74]
Kenechukwu FC, Attama AA, Ibezim EC, et al. Novel intravaginal drug delivery system based on molecularly pegylated lipid matrices for improved antifungal activity of miconazole nitrate. BioMed Res Int 2018; 2018: 1-18.
[http://dx.doi.org/10.1155/2018/3714329] [PMID: 29977910]