FORMULATION AND EVALUATION OF GASTRO-RETENTIVE DRUG DELIVERY SYSTEM OF NOVEL FAMOTIDINE PHOSPHOLIPID COMPLEX
Abstract
Famotidine is an H2 receptor antagonist belonging to the BCS Class II, characterized by low solubility and limited oral bioavailability. The current study encompasses the formulation of novel Famotidine phospholipid complex (FHC) with the aid of design of experiments (Central Composite Design) using solvent evaporation technique to overcome the disadvantages of Famotidine. To further enhance the physicochemical properties of FHC, it was incorporated into gastro-retentive floating tablets (GRDDS) using direct compression technique with sodium bicarbonate as a gas generating agent and its properties were compared to Famotidine floating tablets. The pre-compression parameters namely bulk density, tapped density, Hausner’s ratio, Carr’s compressibility index and angle of repose were evaluated and the flow properties of FHC granules were found to be better than the plain Famotidine granules. The post compression parameters namely thickness, hardness, friability, weight variation, drug content and swelling index showed better results for FHC as compared to Famotidine floating tablets. In vitro buoyancy study indicated that the floating lag time for FHC tablets (110±0.021 seconds) was higher than Famotidine tablets (36±0.033 seconds) owing to the higher molecular weight of phosphatidylcholine. But the total floating time for FHC tablets was found to be more than 18 hours and for Famotidine tablets it was ~12 hours indicating the improved residence time and buoyancy. The in vitro dissolution study depicted that the cumulative release for FHC tablets (99.84±0.058%) was enhanced 1.07 fold than Famotidine tablets (92.73±0.028%) and 1.6 fold than marketed tablet, Famocid (62.24±0.023%). When kinetic modelling was performed, Famotidine tablet followed zero order kinetics whereas FHC tablet followed Higuchi model indicating a modified and sustained release pattern. The statistical analysis for % cumulative release performed using ANOVA and Dunnett’s test showed the p value to be below 0.05 (0.0043) indicating that the analysis model was significant. An accelerated stability study was performed for a period of 6 months at 25±2°C; 60±5% RH. FHC tablets showed a better stability profile than Famotidine tablets. In conclusion, FHC gastro-retentive floating tablets showed improved flow properties, post compression properties, better drug content, improved in vitro buoyancy and enhanced cumulative release and stability profile.
Keywords:
Gastro-retentive drug delivery, Famotidine phospholipid complex, Floating tablet, In vitro buoyancy study, In vitro dissolution, Kinetic modellingDOI
https://doi.org/10.25004/IJPSDR.2023.150304References
Ramachandran S, Poovi G, Dhanaraju M. Evaluation of Gastric and Deuodenal Antiulcer Activity of Famotidine Formulation in Experimental Animals. J. Pharmacol. Toxicol. 2011;1–7.
Jha S, Karki R. Evaluation of Antiulcer Activity of Famotidine Loaded Microemulsion on Experimental Animals. J. Chronother. Drug Deliv. 2014; 5(1):19–25.
Patel DJ, Patel J. Design and Evaluation of Famotidine Mucoadhesive Nanoparticles for Aspirin Induced Ulcer Treatment. Braz Arch Biol Technol. 2013; 56:223–236.
Nair R, Ashok Kumar CK, Arun Kumar KS, Vishnu Priya K, Thusahra Bindu M, Prasannaraju Y. Formulation and Characterization of Famotidine Loaded Chitosan Solid Lipid Nanoparticles for Antiulcer Activity. J. Pharm. Sci. Res. 2012; 4(4):1797–1802.
Shoaib MH, Al S, Siddiqi S, Yousuf RI, Zaheer K, Hanif M, Rehana S, Jabeen S. Development and Evaluation of Hydrophilic Colloid Matrix of Famotidine Tablets. AAPS PharmSciTech. 2010; 11(2):708–718. https://doi.org/10.1208/s12249-010-9427-7
Thomas V, Bhattachar S, Hitchingham L, Zocharski P, Naath M, Surendran N, Stoner C, El-Kattan A. The Road Map to Oral Bioavailability: An Industrial Perspective. Expert. Opin. Drug. Metab. Toxicol. 2006; 2(4):591–608. https://doi.org/10.1517/17425255.2.4.591
Thakkar H, Patel B, Thakkar S. A Review on Techniques for Oral Bioavailability Enhancement of Drugs. Int. J. Pharm. Sci. Rev. Res. 2010; 4(3):203–223.
Saraf S, Khan J, Alexander A, Ajazuddin, Saraf S. Recent advances and future prospects of phyto-phospholipid complexation technique for improving pharmacokinetic profile of plant actives. J. Control. Release. 2013; 168(1):50–60. https://doi.org/10.1016/j.jconrel.2013.02.025
Amit P, Kumar JS, Harishanker P, Tarkeshwar S, Arpit S. Formulation Development and Evaluation of Famotidine Floating Tablet. Int. J. Pharm. Sci. Rev. Res. 2015; 4(3):224-229.
Pant S, Badola A, Kothiyal P. A Review on Gastro-retentive Drug Delivery System. Int. J. Res. Dev. Pharm. Life Sci. 2016; 5(5):2178-2187.
Narang N. An Update Review on Floating Drug Delivery System. Int. J. Appl. Pharm. 2011; 3(1):1-7.
Vummaneni V, Nagpal D, Surapaneni S. Formulation and Optimization of Famotidine Floating Tablets using 23 Factorial Design. J. Pharm. Res. 2012; 5(12):5280–5284.
Vedha Hari B. The Recent Developments on Gastric Floating Drug Delivery Systems: An Overview. Int. J. Pharmtech. Res. 2010; 2:524-534.
Rocca J, Omidian H, Shah K. Progresses in Gastro-retentive Drug Delivery Systems. Pharmatech. 2003; 3:152-156.
Kumar A, Verma A, Sharma G, Saini R, Sharma S. Formulation and Characterization of Effervescent Floating Matrix Tablets of Famotidine Hydrochloride. Asian J. Biomed. Pharm. Sci. 2013; 03(25):43–47.
Jaimini M, Rana AC, Tanwar Y. Formulation and Evaluation of Famotidine Floating Tablets, Curr. Drug Deliv. 2007; 1:51-55.
Ittadwar P, Puranik P. Novel Umbelliferone Phytosomes: Development and Optimization using Experimental Design Approach and Evaluation of Photo-Protective and Antioxidant Activity. Int. J. Pharm. Pharm. Sci. 2017; 9(1):218–28. https://doi.org/10.22159/ijpps.2017v9i1.14635
Yue P, Yuan H, Li X, Yang M, Zhu W. Process Optimization, Characterization and Evaluation In Vivo of Oxymatrine-Phospholipid Complex. Int. J. Pharm. 2010; 387(1–2):139–46. https://doi.org/10.1016/j.ijpharm.2009.12.008
Ittadwar P, Bhojne S, Puranik P. Novel Salicin Phytosomal Complex: Development and Optimization using Central Composite Design. World J. Pharm. Res. 2018; 7(9):735–51. https://doi.org/10.20959/wjpr20189-11974
Tan Q, Liu S, Chen X, Wu M, Wang H, Yin H, He D, Xiong H, Zhang J. Design and Evaluation of a Novel Evodiamine-Phospholipid Complex for Improved Oral Bioavailability. AAPS PharmSciTech. 2012; 13(2):534–47.
https://doi.org/10.1208/s12249-012-9772-9
The Theory and Practice of Industrial Pharmacy By Lachman and Lieberman (3rd Editn).pdf. (n.d.).
Mohrle, R. Effervescent Tablets. In Pharmaceutical Dosage Forms: Tablets. 1989; 285.
Charagonda S, Puligilla RD, Ananthula MB, Bakshi V. Formulation and Evaluation of Famotidine Floating Microsponges. Int. Res. J. Pharm. 2016; 7(4):62–67. https://doi.org/10.7897/2230-8407.07440
Reddy SV, Badarinath AV, Gnana Prakash K. Formulation and Evaluation of Floating Tablets of Ciprofloxacin Hydrochloride. Asian J. Pharm. 2018; 12(2):106–114.
Chauhan YS, Kataria U, Dashora A. Formulation and Evaluation of Floating Tablet for Indomethacin. J. Drug Deliv. Ther., 2018; 8(4): 338-345. https://doi.org/10.22270/jddt.v8i4.1811
Aswatha H, Lachake P, Kaushik U, Shreedhara C. Formulation and Evaluation of Floating Tablets of Liquorice Extract. Pharmacogn. Res. 2010; 2(5):304-308. https://doi.org/10.4103/0974-8490.72329
Kumari S, Vengatesh S, Elango K, Damayanthi R, Deattu N, Christina P. Formulation and Evaluation of Floating Tablets of Ondansetron Hydrochloride. Int. J. Drug Dev. Res. 2012; 4(4):265–274.
Voleti VK, Shaik HR, Raghu Ram N, Silpa G, Lemati S. Formulation and Evaluation of Gastro Retentive Drug Delivery System of Stavudine. Int. Res. J. Pharm. 2011; 2(2):120–128. http://www.irjponline.com/vol2-issue2/17.pdf
Patel R, Bathe RS, Khobragade D, Jadhav S. Formulation and Evaluation of Gastroretentive Beads of Ranitidine Hydrochloride. Int. J. Pharm. Pharm. Sci. 2014; 6(2):237–242.
Sarkar T, Raju T, Patil BS, Nitalikar. Design and Evaluation of Floating Osmotic Tablet of Nizatidine. Der Pharmacia Sinica. 2014; 5(5):67-73.
Chen YC, Ho, Lee TY, Sheu MT. Physical Characterization and Sustained Release Profiling of Gastroretentive Drug Delivery Systems with Improved Floating and Swelling Capability. Int. J. Pharm. 2013; 44:162-169.
The Indian Pharmacopoeia Commission. Indian Pharmacopeia (IP), Volume I. 2010; 559–560.
Malik A, Kushnoor A, Saini V, Singhal S, Kumar S, Yadav Y. Analytical Method Development of Nutraceutical: Umbelliferone. Int. J. Pharma Sci. 2012; 3(1):67–73.
Agrawal VK, Gupta A, Chaturvedi S. Improvement in Bioavailability of Class-III Drug: Phytolipid Delivery System. Int. J. Pharm. Pharm. Sci. 2012; 4(1):37–42.
Dash S, Murthy PN, Nath L, Chowdhury P. Kinetic Modelling on Drug Release from Controlled Drug Delivery Systems. Acta Pol. Pharm. 2010; 67(3):217–223.
International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. Requirements for Registration of Pharmaceuticals for Human Stability Testing of Q1A(R2) 2003; (February):1–18.
Food and Drug Administration. Liposome Drug Products - Guidance for Industry. Pharmaceutical Quality, Revision 1. 2015; (October):1–13.
Published
Abstract Display: 554 
PDF Downloads: 441 
