Journal of Pharmacy And Bioallied Sciences

ORIGINAL/BRIEF
Year
: 2012  |  Volume : 4  |  Issue : 5  |  Page : 88--89

Design and characterization of controlled release gastro-retentive floating tablet of an atypical psychotropic agent


Ravikumar Ukawala1, Gautam Singhvi1, Suresh Jain2, Vipin Shukla1, Nilesh Yadav1, Sohiny Sharma1,  
1 Department of Pharmacy, B. I. T. S.-Pilani, Pilani, Rajasthan, India
2 Department of Pharmacy, Baroda College of Pharmacy, Baroda, Gujarat, India

Correspondence Address:
Ravikumar Ukawala
Department of Pharmacy, B. I. T. S.-Pilani, Pilani, Rajasthan
India

Abstract

The purpose of the present work was to design and evaluate the once daily sustained release matrix type gastro-retentive floating tablet of Quetiapine Fumarate base on hydrophilic matrices of HPMC, sodium CMC and Carbopol. Sodium bicarbonate was incorporated as a gas-generating agent to give buoyancy. In-vitro drug release studies were performed in pH 1.2 buffer using USP type II paddle at 50 rpm. The release rate of drug decreased with increasing polymer proportion of HPMC K15M from 20 to 60 mg. Formulation with desired drug release achieved with combination of sodium CMC and K15M in ratio of 1:3. The drug release mechanism was predominantly found to be Non-Fickian diffusion and Higuchi controlled.



How to cite this article:
Ukawala R, Singhvi G, Jain S, Shukla V, Yadav N, Sharma S. Design and characterization of controlled release gastro-retentive floating tablet of an atypical psychotropic agent.J Pharm Bioall Sci 2012;4:88-89


How to cite this URL:
Ukawala R, Singhvi G, Jain S, Shukla V, Yadav N, Sharma S. Design and characterization of controlled release gastro-retentive floating tablet of an atypical psychotropic agent. J Pharm Bioall Sci [serial online] 2012 [cited 2022 Aug 12 ];4:88-89
Available from: https://www.jpbsonline.org/text.asp?2012/4/5/88/94151


Full Text

Quetiapine Fumarate (QF) is an atypical psychotropic agent of dibenzothiazepine class. QF shows pH dependent solubility. QF is highly soluble in acidic pH and slightly soluble in basic pH. Gastroretentive floating tablet would be more beneficial to retain the drug in stomach for prolonged duration so as to achieve maximum absorption and bioavailability. [1],[2]

 Materials and Methods



The excipients were selected on the basis of density and functions. [3] Various polymers like HPMC K15M, Sodium CMC, Carbopol alone and in combination in different ration were tried to get desired drug release, short buoyancy lag time and sufficient buoyancy time for prolong drug release. Typical sustained release formulations of QF 200 mg are listed in [Table 1]. Tablets were made by using QF (200 mg each tablet), HPMC (release retardant hydrophilic polymer), sodium CMC, carbopol (release retardant polymer and as a gelling agent), sodium bicarbonate (SB, gas-generating agent) and micro crystalline cellulose (MCC, release modifier and volume expender for granules), by wet granulation process with PVP K30 (3%, w/v, in isopropyl alcohol). Compression was done on a 10 station tablet machine (Rimek mini press, India). The effect of polymer and gas generating agent on drug release, buoyancy lag time and the duration of buoyancy were studied in pH 1.2 buffer using USP type II apparatus at 50 rpm. Drug release and drug content was analyzed spectrophotometrically at 250 nm (UV spectrophotometer, Jasco) with validated UV method.{Table 1}

 Results and Discussion



Compatibility studies of drug with excipients were performed at various conditions as per ICH for one month. Weight variation, drug content and other physical characteristics of designed tablets were found to be acceptable indicating suitability of technique used for manufacturing tablets. In vitro release studies indicated that the release rate of drug decreased with increasing polymer proportion of HPMC K15M from 20 to 60 mg in the formulation [Figure 1]. Few trials were taken for getting floating of tablets for optimization of SB concentration. Buoyancy lag time and the duration of buoyancy [Table 2] were function of proportion of SB and HPMC. It was found that formulation with 40 mg MCC and 100 mg sodium bicarbonate showed minimum buoyancy lag time with sufficient buoyancy time in all proportion of polymer combinations. Trial F-1, F-2, F-5 and F-7 release showed that there was not enough polymer concentration to sustain the drug release. An increase in the polymer concentration causes increase in viscosity of the gel and leads to formation of gel layer with a longer diffusional path thereby retarding the drug release rate. Formulation with carbopol and HPMC (F-4 and F-5) further retarded the drug release with increased floating lag time. Formulation F-3 showed desired drug release and remained floating up to 20 hrs with tablet integrity being maintained throughout. The data obtained from in vitro dissolution studies were fitted in different models viz. zero order, first order, Higuchi model and Peppas model. [4],[5],[6] The drug release mechanism was predominantly found to be Non-Fickian diffusion controlled. Release profile also showed a tendency to follow Higuchi kinetics.{Figure 1}{Table 2}

 Conclusions



It can be concluded formulation with desired drug release achieved with combination of Na CMC and HPMC K15M in ratio of 1:3. The addition of gel forming polymer (HPMC) and gas generating agent (sodium bicarbonate) were essential to achieve in vitro buoyancy. Stable and persistent buoyancy was achieved by trapping gas in gel formed by hydration of HPMC and Na CMC polymer.

References

1Mullen J, Jibson MD, Sweitzer D. A comparison of the relative safety, efficacy, and tolerability of quetiapine and risperidone in outpatients with schizophrenia and other psychotic disorders: The Quetiapine Experience with Safety and Tolerability study. Clin Ther. 2001;23:1839-54.
2Figueroa C, Brecher M, Hamer-Maansson JE, Winter H. Pharmacokinetic profiles of extended release quetiapine fumarate compared with quetiapine immediate release. Prog Neuropsycho -pharmacol Biol Psychiatry. 2009;33:199-204.
3Deshpande AA, Shah NH, Rhodes CT, Malick W. Development of a novel controlled-release system for gastric retention. Pharm Res. 1997;14:815-19.
4Singh BN, Kim KH. Floating drug delivery systems: An approach to oral controlled drug delivery via gastric retention. J Control Release. 2000;63:235-59.
5Groning R, Heun G. Oral dosage forms with controlled gastrointestinal transit. Drug Dev Ind Pharm. 1984;10:527-39.
6Baumgartner S, Kristel J, Vreer F, Vodopivec P, Zorko B. Optimisation of floating matrix tablets and evaluation of their gastric residence time. Int J Pharm. 2000;195:125-35.