Floating and bioadhesive delivery system of metoprolol succinate: Formulation, development and in vitro evaluation

Main Article Content

Mohan Rathi
Rohan Medhekar
Ashish Pawar
Chetan Yewale
Vilas Gudsoorkar

Abstract

Aim of this study was to develop gastroretentive sustained release floating and bioadhesive drug delivery system (FBDDS) to prolong the gastric retention time of Metoprolol succinate. Tablets were prepared employing hydroxypropyl
methylcellulose (HPMC K100M) as hydrophilic gel material, sodium bicarbonate as gas-generating agent and Sodium CMC (SCMC) as bioadhesive polymer. A 32 full factorial design and response surface methodology were used for designing of
experiment, mapping change in responses and deriving optimum formulation. Selected independent variables were amounts HPMC K100M and SCMC polymer while floating lag time (FLT), bioadhesive strength, t50 (time taken to release 50% of drug) and t90 (time taken to release 90% of drug) were selected as dependent variables. Investigation of functionality of individual polymer to predict effect on dependent variable were statistically analyzed using the RSM.Tablets were also evaluated for physical properties, swelling and matrix erosion. Increase in concentration of HPMC and decrease in concentration of SCMC resulted in retardation of drug release. Furthermore, combination of HPMC K100M and sodium bicarbonate along with SCMC was found to affect buoyancy, bioadhesion strength and drug release. Optimized formulation showed values of
dependent variables close to predicted values. Optimized formulation follows Higuchi kinetics with short buoyancy lag time, total buoyancy time of more than 24 hours and could maintain drug release for 24 hours. Content uniformity, hardness, friability, weight variation were all lying within limits. Hence, FBDDS was found to be very promising and alternative approach to increase gastric retention of dosage form and may improve bioavailability.

Downloads

Download data is not yet available.

Article Details

How to Cite
Rathi, M., Medhekar, R., Pawar, A., Yewale, C., & Gudsoorkar, V. (2014). Floating and bioadhesive delivery system of metoprolol succinate: Formulation, development and in vitro evaluation. Asian Journal of Pharmaceutics (AJP), 6(3). https://doi.org/10.22377/ajp.v6i3.217
Section
Articles

References

Mikos AG, Peppas NA. Bioadhesive analysis of controlled-release

systems. IV. An experimental method for testing the adhesion of

microparticles with mucus. J Control Release 1990;12:31-7.

Hong SI, Oh SY. Dissolution kinetics and physical characterization of

three-layered tablet with poly(ethylene oxide) core matrix capped by

Carbopol. Int J Pharm 2008;356:121-9.

McGinity JW, Koleng JJ, Repka MA, Zhang F. Hot melt extrusion

technology. In: Swarbrik J, editor. Encylopedia of Pharmaceutical

Techonology. 3rd ed. New York: Informa Healthcare USA, Inc; 2005. p.

-20.

Trotta M, Gasco MR, Morel S. Release of drugs from oil-water

microemulsions. J Control Release 1989;10:237-43.

Chavanpatil MD, Jain P, Chaudhari S, Shear R, Vavia P. Development of

sustained release gastroretentive drug delivery system for ofloxacin:

In vitro and in vivo evaluation. Int J Pharm 2005;304:178-84.

Deshpande AA, Rhodes CT, Shah NH, Malick AW. Controlled-Release

Drug Delivery Systems for Prolonged Gastric Residence: An Overview.

Drug Dev Ind Pharm 1996;22:531-9.

Hwang SJ, Park H, Park K. Gastric retentive drug-delivery systems. Crit

Rev Ther Drug Carrier Syst 1998;15:243-84.

Arora S, Ali J, Ahuja A, Khar RK, Baboota S. Floating drug delivery

systems: A review. AAPS PharmSciTech 2005;6:E372-90.

Rouge N, Buri P, Doelker E. Drug absorption sites in the gastrointestinal

tract and dosage forms for site-specific delivery. Int J Pharm

;136:117-39.

Bardonnet PL, Faivre V, Pugh WJ, Piffaretti JC, Falson F. Gastroretentive

dosage forms: Overview and special case of Helicobacter pylori. J

Control Release 2006;111:1-18.

Garg S, Sharma S. Gastroretentive drug delivery systems. Business

Briefing, Available on http://www.touchbriefings.com 2003;160-6.

Klausner EA, Lavy E, Friedman M, Hoffman A. Expandable gastroretentive

dosage forms. J Control Release 2003;90:143-62.

Singh BN, Kim KH. Floating drug delivery systems: An approach to

oral controlled drug delivery via gastric retention. J Control Release

;63:235-59.

14. Baumgartner S, Kristl J, VreÄer F, Vodopivec P, Zorko B. Optimization

of floating matrix tablets and evaluation of their gastric residence time.

Int J Pharm 2000;195:125-35.

Khosla R, Davis SS. The effect of tablet size on the gastric emptying of

non-disintegrating tablets. Int J Pharm 1990;62:R9-R11.

Mojaverian P, Vlasses PH, Kellner PE, Rocci ML Jr. Effects of gender,

posture, and age on gastric residence time of an indigestible solid:

Pharmaceutical considerations. Pharm Res 1988;5:639-44.

Srivastava AK, Wadhwa S, Ridhurkar D, Mishra B. Oral sustained

delivery of atenolol from floating matrix tablets formulation and in vitro

evaluation. Drug Dev Ind Pharm 2005;31:367-74.

Chueh HR, Zia H, Rhodes CT. Optimization of sotalol floating and

bioadhesive extended release tablet formulations. Drug Dev Ind Pharm

;21:1725-47.

Deshpande AA, Shah NH, Rhodes CT, Malick W. Development of a

novel controlled-release system for gastric retention. Pharm Res

;14:815-9.

Ingani HM, Timmermans J, Moës AJ. Conception and in vivo investigation

of peroral sustained release floating dosage forms with enhanced

gastrointestinal transit. Int J Pharm 1987;35:157-64.

Dave BS, Amin AF, Patel MM. Gastroretentive drug delivery system of

ranitidine hydrochloride: Formulation and in vitro evaluation. AAPS

PharmSciTech 2004;5:e34.

Chowdary KP, Suresh B, Sangeeta B, Reddy GK. Design and evaluation

of diltiazem mucoadhesive tablets for oral controlled release. Saudi

Pharm J 2003;11:201-5.

Varshosaz J, Tavakoli N, Roozbahani F. Formulation and in vitro

characterization of ciprofloxacin floating and bioadhesive extended-

release tablets. Drug Deliv 2006;13:277-85.

Hoffman BB. Therapy of Hypertension. In: Brunton LL, Lazo JS,

Parker KL, editors. Goodman and Gilman’s the pharmacological basis

of therapeutics. 11th ed. New York: McGraw-Hill; 2006. p. 845-68.

Kendall MJ, Maxwell SR, Sandberg A, Westergren G. Controlled release

metoprolol. Clinical pharmacokinetic and therapeutic implications. Clin

Pharmacokinet 1991;21:319-30.

Feliciano NR, Bouvet AA, Redalieu E, Castellana J, Luders RC,

Schwartz DJ, et al. Pharmacokinetic and pharmacodynamic comparison

of an osmotic release oral metoprolol tablet and the metoprolol

conventional tablet. Am Heart J 1990;120:483-9.

Good W, Leeson LJ, Zak SL, Wagner WE, Meeker JB, Arnold JD. Oros

controlled-release formulations of metoprolol: An approach to the

development of a system for once daily administration. Br J Clin

Pharmacol 1985;19 Suppl 2:231S-8S.

Lucker P, Moore G, Wieselgren I, Olofsson B, Bergstrand R.

Pharmacokinetic and pharmacodynamic comparison of metoprolol

CR/ZOK once daily with conventional tablets once daily and in divided

doses. J Clin Pharmacol 1990;30(2 Suppl):S17-27.

Sandberg A, Abrahamsson B, Svenheden A, Olofsson B, Bergstrand R.

Steady-state bioavailability and day-to-day variability of a multiple-unit

(CR/ZOK) and a single-unit (OROS) delivery system of metoprolol after

once-daily dosing. Pharm Res 1993;10:28-34.

Kendall M, Akhlaghi S, Hughes B, Lewis H. Is metoprolol CR/ZOK more

selective than conventional metoprolol and atenolol? J Clin Pharmacol

;30(2 Suppl):S98-102.

Cochran WG, Cox GM. Experimental designs. 2nd ed. New York: John

Wiley and Sons, Inc; 1957.

Bhavsar MD, Tiwari SB, Amiji MM. Formulation optimization for the

nanoparticles-in-microsphere hybrid oral delivery system using factorial

design. J Control Release 2006;110:422-30.

Singh B, Ahuja N. Response surface optimization of drug delivery

system. In: Jain NK, editor. Progress in controlled and novel drug

delivery systems. 1 st ed. New Delhi, India: CBS Publishers and

Distributors; 2004. p. 470-9.

Singh B, Ahuja N. Pharmaceutical experimental design (Drugs and the

Pharmaceutical Sciences, Vol. 92). In: Lewis GA, Mathieu D, Phan-Tan-

Luu R, editors. 1st ed. New York: Marcel Dekker; 1999. p. 498. Int J

Pharm 2000;195:247-8.

Singh B, Dahiya M, Saharan V, Abuja N. Optimizing drug delivery

systems using systematic design of experiments. Part II: Retrospect

and prospects. Crit Rev Ther Drug Carrier Syst 2005;22:215-93.

Singh B, Kumar R, Abuja N. Optimizing drug delivery systems using

systematic design of experiments. Part I: Fundamental aspects. Crit

Rev Ther Drug Carrier Syst 2005;22:27-105.

USP: United States Pharmacopoeia. 23rd ed. United States of America:

Twin Brook Park Wag; 2006.

Chavanpatil MD, Jain P, Chaudhari S, Shear R, Vavia PR. Novel sustained

release, swellable and bioadhesive gastroretentive drug delivery system

for ofloxacin. Int J Pharm 2006;316:86-92.

Lalla JK, Gurnancy RA. Polymers for mucosal delivery-swelling and

mucoadhesive delivery. Indian Drugs 2002;39:270-6.

Grabovac V, Guggi D, Bernkop-Schnurch A. Comparison of the

mucoadhesive properties of various polymers. Adv Drug Deliv Rev

;57:1713-23.

Tamburic S, Craig DQ. A comparison of different in vitro methods

for measuring mucoadhesive performance. Eur J Pharm Biopharm

;44:159-67.

Peppas NA, Huang Y. Nanoscale technology of mucoadhesive

interactions. Adv Drug Deliv Rev 2004;56:1675-87.

Dorozynski P, Jachowicz R, Kulinowski P, Kwiecinski S, Szybinski K,

Skorka T, et al. The macromolecular polymers for the preparation of

hydrodynamically balanced systems--methods of evaluation. Drug Dev

Ind Pharm 2004;30:947-57.

Costa P, Sousa Lobo JM. Modeling and comparison of dissolution

profiles. Eur J Pharm Sci 2001;13:123-33.

Shah VP, Tsong Y, Sathe P, Liu JP. In vitro dissolution profile comparison--

statistics and analysis of the similarity factor, f2. Pharm Res 1998;15:889-96.

Mazzo DJ. International stability testing. USA: Interpharm press, Inc;

Whitehead L, Fell JT, Collett JH, Sharma HL, Smith A. Floating

dosage forms: An in vivo study demonstrating prolonged gastric

retention. J Control Release 1998;55:3-12.

Bolton S, Bon C. Pharmaceutical statistics: Practical and clinical

applications. 5th ed. New York: Marcel Dekker, Inc; 2010.

Schwartz JB, O’Connor RE, Schnaare RL. Optimization techniques in

pharmaceutical formulation and processing. In: Banker GS, Rhodes CT,

editors. Modern pharmaceutics. 4 th Revised and Expanded ed.

New York: Marcell Dekker, Inc; 2002. p. 607-26.