EFFECTS OF FORMULATION PARAMETERS ON PROPERTIES OF GASTRIC FLOATING TABLETS CONTAINING POORLY SOLUBLE DRUG: DICLOFENAC SODIUM
Keywords:Diclofenac sodium, Floating tablet, HPMC, SLS
Objective: The objective of this study was to prepare and investigate the effects of formulation parameters on the properties of gastric floating tablets containing diclofenac sodium (DICL) as a model of poorly soluble acidic drug, sodium bicarbonate (NaHCO3) or calcium carbonate (CaCO3) as gas-forming agent, hydroxypropyl methylcellulose (HPMC) K100M or K15M as swelling polymer and sodium lauryl sulfate (SLS) as wetting agent.
Methods: DICL floating tablets were prepared using direct compression method. The compressed tablets were evaluated for tablet properties, swelling index, and in vitro buoyancy. The in vitro release under non-sink condition was determined. Molecular interaction was studied using differential scanning calorimetry and fourier transform infrared spectroscopy.
Results: The tablet properties of all DICL floating tablets were within the acceptance criteria. The molecular interaction between DICL and excipients in the formulation was excluded. Depends on the formulation compositions, the swelling index at 3 h (SI) ranged from 44Â±11 to 1158Â±33 %, whereas the buoyancy properties namely floating lag time (FLT) and total floating time (TFT) were 0.33Â±0.03 to 10.04Â±0.04 min and 10.0Â±0.0 to>12 h, respectively. NaHCO3 showed higher swelling, buoyancy and release properties compared to those of CaCO3. NaHCO3 at 20% gave sufficient swelling (SI of 1074Â±16 %), buoyancy (FLT of 0.39Â±0.03 min, TFT of>12 h) and release properties (cumulative release of 5.83Â±0.02 %). HPMC K100M showed better swelling property of which its initial swelling rate was 1412Â±25 %/h compared to HPMC K15M (1042Â±31 %/h). HPMC K100M at 20% showed better buoyancy and release properties compared to those obtained from HPMC K100M at 30%. The release testing under non-sink conditions was able to distinguish the effect of formulation parameters on the DICL release profiles. Incorporation of SLS at 0.25% could enhance both release rate and cumulative release of DICL from the floating tablets. Nevertheless, it showed the unacceptable adverse effect on swelling and buoyancy properties of DICL floating tablets. The TFT of DICL floating tablets containing 0.25% SLS was only 0.5Â±0.0 h.
Conclusion: DICL floating tablets were successfully prepared. Tablets possessing suitable swelling and buoyancy properties were obtained using NaHCO3 at 20% as a gas-forming agent, with HPMC K100M at 10 and 20% as floating matrix and swelling polymer. Addition of SLS as wetting and solubilizing agent showed the unacceptable adverse effect on the swelling and buoyancy properties of DICL floating tablets. The release under sink conditions and/or in vivo pharmacokinetic studies shall be further performed.
Jagdale SC, Agavekar AJ, Pandya SV, Kuchekar BS, Chabukswar AR. Formulation and evaluation of gastroretentive drug delivery system of propranolol hydrochloride. AAPS PharmSciTech 2009;10:1071-9.
Yin L, Qin C, Chen K, Zhu C, Cao H, Zhou J, et al. Gastro-floating tablets of cephalexin: preparation and in vitro/in vivo evaluation. Int J Pharm 2013;452:241-8.
Singh BN, Kim KH. Floating drug delivery systems: an approach to oral controlled drug delivery via gastric retention. J Controlled Release 2000;63:235-59.
Lopes CM, Bettencourt C, Rossi A, Buttini F, Barata P. Overview on gastroretentive drug delivery systems for improving drug bioavailability. Int J Pharm 2016;510:144-58.
Bardonnet PL, Faivre V, Pugh WJ, Piffaretti JC, Falson F. Gastroretentive dosage forms: overview and special case of helicobacter pylori. J Controlled Release 2006;111:1-18.
Tadros MI. Controlled-release effervescent floating matrix tablets of ciprofloxacin hydrochloride: development, optimization and in vitro-in vivo evaluation in healthy human volunteers. Eur J Pharm Biopharm 2010;74:332-9.
Pawar VK, Kansal S, Garg G, Awasthi R, Singodia D, Kulkarni G. Gastroretentive dosage forms: a review with special emphasis on floating drug delivery systems. Drug Delivery 2011;18:97-110.
Manjunath PN, Satish CS, Vasanti S, Preetham AC, Maidu Ras. Formulation and evaluation of simvastatin gastroretentive drug delivery system. Int J Appl Pharm 2017;9:55-60.
Albadry AA, Ali WK, Al-Saady FA. Formulation and evaluation of prochlorperazine maleate sustained floating release tablet. Int J Pharm Pharm Sci 2017;9:89-98.
Mali AD, Bathe RS. Development and evaluation of gastroretentive floating tablet of a quinapril HCl by direct compression technique. Int J Pharm Pharm Sci 2017;9:35-46.
Wolters K. Drug information handbook with international trade names index. 24thed. Ohio: LEXI-COMP; 2015.
Ho HO, Liu CH, Lin HM, Sheu MT. The development of matrix tablets for diclofenac sodium based on an empirical in vitro and in vivo correlation. J Controlled Release 1997;49:149-56.
Kapsi SG, Ayres JW. Processing factors in development of solid solution formulation of itraconazole for enhancement of drug dissolution and bioavailability. Int J Pharm 2001;229:193â€“203.
Javadzadeh Y, Jafari-Navimipour B, Nokhodchi A. Liquisolid technique for dissolution rate enhancement of a high dose water-insoluble drug (carbamazepine). Int J Pharm 2007;341:26-34.
Shokri J, Ahmadi P, Rashidi P, Shahsavari M, Rajabi Siahboomi A, Nokhodchi A. Swellable elementary osmotic pump (SEOP): an effective device for delivery of poorly water-soluble drugs. Eur J Pharm Biopharm 2008;68:289â€“97.
Moore F, Okelo G, Colon I, Kushner J. Improving the hardness of dry granulated tablets containing sodium lauryl sulfate. Int J Pharm 2010;400:37-41.
Patel VF, Patel NM. Intragastric floating drug delivery system of cefuroxime axetil: in vitro evaluation. AAPS PharmSciTech 2006;7:118-24.
United States Phaemacopeia and National Formulary (USP 39-NF 34). Rockville MD. United States Pharmacopeial Convention; 2015.
Bhoi P, Dash RK, Dalai MK. Formulation and in vitro evaluation of oral floating matrix tablets of diclofenac sodium. Int J PharmTech Res 2010;2:2420-8.
Hu L, Li L, Yang X, Liu W, Yang J, Jia Y, et al. Floating matrix dosage form for dextromethorphan hydrobromide based on gas forming technique: in vitro and in vivo evaluation in healthy volunteers. Eur J Pharm Sci 2011;42:99-105.
Siewert M, Dressman J, Brown CK, Shah VP, FIP, AAPS. FIP/AAPS guidelines to dissolution/in vitro release testing of novel/special dosage forms. AAPS PharmSciTech 2003;4:E7.
Nagarwal RC, Ridhurkar DN, Pandit JK. In vitro release kinetics and bioavailability of gastroretentive cinnarizine hydro-chloride tablet. AAPS PharmSciTech 2010;11:294-303.
Timmermans J, Andre JM. Factors controlling the buoyancy and gastric retention capabilities of floating matrix capsules: new data for reconsidering the controversy. J Pharm Sci 1994;83:18-24.
Li S, Lin S, Daggy BP, Mirchandani HL, Chien TW. Effect of formulation variables on the floating properties of gastric floating drug delivery system. Drug Dev Ind Pharm 2002;28:783-93.
Rowe RC, Sheskey PJ, Quinn ME. Handbook of pharmaceutical excipients. 6th ed. Gurnee (IL): Pharmaceutical Press; 2009.
Rao GK, Mandapalli PK, Manthri R, Reddy VP. Development and in vivo evaluation of gastroretentive delivery systems for cefuroxime axetil. Saudi Pharm J 2013;21:53-9.
Hoffman A, Qadri BA. Gastro-retentive systems. In: James Swarbrick. Ed. Encyclopedia of pharmaceutical technology. 3rd ed. Vol. 1. NY: Informa healthcare; 2007. p. 1850-60.
Padmavathy J, Saravanan D, Rajesh D. Formulation and evaluation of ofloxacin floating tablets using HPMC. Int J Pharm Pharm Sci 2011;3:170-3.
Peppas NA, Khare AR. Preparation, structure and diffusional behavior of hydrogel in controlled release. Adv Drug Delivery Rev 1993;11:1â€“35.
Bertram U, Bodmeier R. In situ gelling, bioadhesive nasal inserts for extended drug delivery: in vitro characterization of a new nasal dosage form. Eur J Pharm Sci 2006;27:62-71.
HasÃ§iÃ§ek C, YÃ¼ksel Tilkan G, TÃ¼rkmen B, Ozdemir N. Effect of formulation parameters on the drug release and floating properties of gastric floating two-layer tablets with acetylsalicylic acid. Acta Pharm 2011;61:303-12.
Jagdale SC, Ghorpade SA, Kuchekar BS, Chabukswar AR. Effect of polymer and gas forming agent on floating drug delivery of tramadol hydrochloride using response surface methodology: in vitro and in vivo evaluation. Int J Pharm Appl 2011;2:181-94.
Jaimini M, Rana AC, Tanwar YS. Formulation and evaluation of famotidine floating tablets. Curr Drug Delivery 2007;4:51-5.
Someshwar K, Chithaluru K, Ramarao T, Kumar K. Formulation and evaluation of effervescent floating tablets of tizanidine hydrochloride. Acta Pharm 2011;61:217-26.
Hari V, Sathiyaraj S, Devi R. Lornoxicam gastro-retentive floating matrix tablets: design and in vitro evaluation. J Adv Pharm Technol Res 2011;2:156-62.
Mohapatra S, KumarKar R, Mohapatra DK, Sahoo SK, Barik BB. Cefuroxime axetil loaded gastroretentive floating tablets based on hydrophilic polymers: preparation and in vitro evaluation. Braz Arch Biol Technol 2012;55:269-75.
Cwiertnia B, Hladon T, Stobiecki M. Stability of diclofenac sodium in the inclusion complex with beta-cyclodextrin in the solid state. J Pharm Pharmacol 1999;51:1213-8.
Mura P, Moyano JR, Gonzalez-Rodriguez ML, Rabasco-Alvarez AM, Cirri M, Maestrelli F. Characterization and dissolution properties of ketoprofen in binary and ternary solid dispersions with polyethylene glycol and surfactants. Drug Dev Ind Pharm 2005;31:425-34.
Kebebe D, Belete A, Gebre-Mariam T. Evaluation of two olibanum resins as rate controlling matrix forming excipients in oral sustained-release tablets. Ethiop Pharm J 2010;28:95-109.