Formulation and Evaluation of Sustained Release Matrix Tablets Ofsalbutamol Sulphate Using

FORMULATION AND EVALUATION OF SUSTAINED RELEASE MATRIX TABLETS OFSALBUTAMOL SULPHATE USING VARIOUS POLYMERS

M. Pharm. Dissertation Protocol Submitted to

RajivGandhiUniversity of Health Sciences, Karnataka

Bangalore – 560041

By

Mr. INDRALE SUNIL V. B.Pharm

Under the Guidance of

Prof. A.M. GODBOLE. M.Pharm.

DEPT. OF PHARMACEUTICS

Post Graduate Department of Pharmaceutics

SET’S College of Pharmacy,

S.R. Nagar, Dharwad.

Karnataka -580002.

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA

ANNEXURE –II

PROFORMA FOR REGISTRATION OF SUBJECT DISSERTATION

1. / NAME OF THE CANDIDATE AND ADDRESS / MR. INDRALE SUNIL VISHWANATHRAO
DEPT. OF PHARMACEUTICS
SET’s COLLEGE OF PHARMACY
S.R.NAGAR,
DHARWAD-580002.
2. / NAME OF THE INSTITUTION / SET’s COLLEGE OF PHARMACY
S. R. NAGAR,
DHARWAD-580002.
3. / COURSE OF STUDY AND SUBJECT / MASTER OF PHARMACY IN PHARMACEUTICS
4. / DATE OF ADMISSION TO THE COURSE / JUNE-2010
5. / TITLE OF THE PROJECT:
FORMULATION AND EVALUATION OF SUSTAINED RELEASE MATRIX TABLETSOFSALBUTAMOL SULPHATE USING VARIOUS POLYMERS
6.0
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8 / BRIEF RESUME OF THE INTENDED WORK:
6.1 NEED FOR STUDY:
Asthma is an extremely commondisorder which affects many people. Asthma is viewedas an inflammatory illness that has bronchial hyperactivityand bronchospasm. Continuous therapy isrequired for the treatment of asthma. Salbutamolsulphate is used as a bronchodilator in the managementof reversible airways obstruction in case of asthma andin some patients with chronic obstructive pulmonarydisease.1
Salbutamol sulphate (SS), a short acting highly selective beta 2 adrenoceptor agonist with bronchodilating property is widely used for the management of Chronic Obstructive Pulmonary Disease (COPD) which includes bronchial asthma, chronic bronchitis and emphysema. Salbutamol sulphate is almost completely absorbed from the gastrointestinal tract after oral administration. The reported plasma half-life of Salbutamol sulphate is 2.85±0.85 and the peak plasma concentration occurs about 30 minutes after an oral dose. The protein binding affinity of Salbutamol sulphate 7±1% and undergoes considerable first pass metabolism. The drug as sulphate is soluble in 1 to 4 of water, due to the hydrophilic nature it is readily excreted through urine.2
The usual goal of a sustained release product is to maintain therapeutic blood levels over an extended period. It is usually intended for drugs to permeate to the general circulation and perfuse to other body tissues. Therapeutic compounds with short half lives are excellent candidates for sustained release preparations, since this can reduce dosing frequency. Sustained release systems usually tend to mimic zero order release by providing drug in a slow manner3.
Chronic obstructive pulmonary diseases (COPD) include bronchial asthma, chronic bronchitis and emphysema. These three disorders differ in their etiology but have one common characteristics i.e. airway obstruction which blocks effective pulmonary ventilation. Sustained release dosage forms are designed to complement the pharmaceutical activity of the medicament in order to achieve better selectivity and longer duration of action.4
Sustained release matrix tablets are relatively easy to fabricate by incorporating drug particles in slowly disintegrating or inert porous materials. Drug release occurs either by diffusion through the matrix or by erosion of the matrix or by a combination of both diffusion and erosion.2 Oral sustained release dosage forms have been used to improve therapeutic efficacy and patient compliance5.
6.2 REVIEW OF LITERATURE:
Ghosh A et al.,investigated the formulation, development and invitro evaluation of sustained release matrix tablets of Salbutamol sulphate.The objective of this study was to develop Salbutamol sulphate matrix tablets for the treatment of chronic obstructive pulmonary disease (COPD). Simultaneous equations were formed to calculate the concentration values of Salbutamol sulphate and drug compatibility through infrared spectroscopy. The matrix tablets were prepared by wet granulation method using two hydrophobic polymers such as Ethyl cellulose and Acrycoat S-100 in varying ratios. The granules exhibited satisfactory rheological behavior.2
Dandagi PM et al.,studied the development and evaluation of Theophylline and Salbutamol sulphate sustained release matrix tablets. The matrix tablets were prepared by wet granulation method using hydroxypropylmethylcellulose K4M and K15M in various percentages. The results of formulation containing 20% hydroxypropylmethylcellulose of grade K15M and K4M in 1:2 ratios extended the release of Theophylline and Salbutamol sulphate up to 12 hrs. and was found to be comparable with marketed sustained release tablet.4
Merekar ANet al.,studied the formulation and in vitro-in vivo evaluation of Salbutamol sulphate sustained release tablets.Invitro dissolution of Salbutamol sulphate was compaired with marketed Asthalin-SA tablet and f2 value was found to be 99.70, which showed that formulated tablet had similar release profile as that of marketed tablet. From the above, conclusion was drawn that the ion exchange resins INDION 244,coupled with tablet could serve as useful tool for sustained release of water soluble drug Salbutamol sulphate.Thus INDION244 Salbutamol sulphate when formulated as tablet using Avicel, Magnesium Sterate & talc provided sustained release, which satisfied the criteria for zero order sustained release. Thus, formulated tabletprovided pH independent sustained release of Salbutamol sulphate and good stability.6
Walekar RB et al.,studid the optimization of Salbutamol sulphate dissolution from sustained release matrix formulations using an artificial neural network.A multi layer perceptron with one hidden layer was constructed usingMatlab and the number of nodes in the hidden layer was optimized by trial and error todevelop a model with the best predictive ability. The results revealed that a neural networkwith nine nodes was optimal for developing and optimizing formulations. Theoptimized neural network was used for optimization of formulation withdesirable releasecharacteristics and the results indicated that there was agreement between the predictedformulation and the manufactured formulation. This work illustrated the possible utility ofartificial neural networks for the optimization of pharmaceutical formulations withdesirable
performance characteristics.7
SolinisMA et al.,investigated the release of Salbutamol sulphate enantiomers from hydroxypropylmethylcellulose matrices. The results obtained showed that there were no enantio selectiveinteractions between Salbutamol sulphate enantiomers and hydroxypropylmethylcellulose that can influence its release. The addition of other chiral compounds such as Dimethyl cyclodextrin and the modification of pH of the tablets did not provide an enantio selective release of Salbutamol sulphate for these formulations in the assayed conditions.8
Hernandez RM et al.,studied thecorrelation of in vitro release and in vivo absorption characteristics of four Salbutamol sulphate formulations.The purpose of this study was to investigate the possibility to develop different levels of correlation between invitro dissolution parameters and in vivo pharmacokinetic parameters for four Salbutamol Sulphate formulations:two commercially available formulations (Ventolin Oral and Volmax) and two sustained release formulations (SG7and SG14) developed. A level A correlation of in vitro release and in vivo absorption was set up for individual plasma level data by means of the deconvolution method.9
Furlanetto S et al.,studied the formulation variables influencing the drug release ratefrom matrix tablets by experimental design. Experimental design strategy have shown to be a veryuseful tool in preformulation studies aimed at thedevelopment of sustained-release formulations based onmatrix-tablets, allowing a rapid, systematic and reliablescreening to identify and quantitatively define the significantfactors influencing the drug release.In particular, graphic analysis of the effects enabledidentification for each examined drug of the formulationfactors active on the selected responses, i.e. t10% and dissolution efficiency,and determination of their best level for the responseoptimisation.10
Ferrero C et al., studied the effect of polymer moisture content on drug release behaviour from Methyl methacrylate-Starch matrix tablets. Both the water content of the copolymer and the type ofdrug influenced the compaction characteristics of the mixtures.Although the plasticising effect of water improvedthe binding properties at 25–50% relative humiditiesconditions, the surfacialcontaminant effect of multilayer adsorbed water makesdifficult the union formation at 75% relative humidities, being necessaryto apply higher maximum upper punch pressures to obtainthe desired crushing force (70–80 N).Concerning the drug, the incorporation of Salbutamolsulphate led to worse compression and frictionproperties than the addition of anhydrous Theophylline inthe formulations.The drug dissolution rate and drug release mechanismfrom the matrices evaluated were clearly conditioned bythe type of drug, so that lower dissolution rates and
a Fickiandiffusion mechanism were identified for anhydrousTheophylline formulations while fasterdissolution ratesand an anomalous transport were postulated for matricescontaining Salbutamol sulphate.11
Bhupendra G. Prajapti. et al.,prepared and studied matrix tablet of Nicorandil. It was evident from the results that a matrix tablet prepared with hydrophilic polymer and hydrophobic polymer is a better system for once-daily sustained release of a highly watersolubledrug like Nicorandil. All formulations exhibited diffusion-dominated drug release.12
Raghavendra Rao NG.etal., studied the formulation and evaluation of sustained release matrixtablets of Tramadol hydrochloride. They prepared formulations with drug: polymer ratio 1:1 show 100% drug release in 6 to 8 hrs and formulations prepared with drug: polymer ratio 1:2 could retard the drug release up to desired time period. The tablets containing polymer blend of hydroxypropylmethylcellulose K15M and Karaya gum (KG)retard the drug release because both are swellable polymer. The tablets containing polymer blend of hydroxypropylmethylcelluloseK15M and Carrageenan (CG)retard the drug release. From the release study it was observed that as we increase the concentration of hydroxypropylmethylcellulose, the release of drug is decreased. This is possibly due to slower erosion of hydroxypropylmethylcellulose and may be due to the increased viscosity of Carrageenan(CG) which might have helped to keep the hydrated gel intact thus releasing the drug for 12 hrs.13
Reddy KR et al.,formulated the sustained release matrix tablets of Nicorandil. The hydrophilic matrix of hydroxypropylmethylcellulosealone did not control the Nicorandil release effectively for 24 hrs. It is evident from the results that a matrix tablet prepared with hydroxypropylmethylcelluloseand a granulating agent of a hydrophobic polymer (ethyl cellulose, 4% wt/vol) was a better system for once a daily sustained release of a highly water-soluble drug like Nicorandil.14
6.3OBJECTIVES OF STUDY:
To carry out compatibility studies between drug and polymer.
To formulate sustained release tablets containing antiasthmatic drug (Salbutamol sulphate)using various polymers with different ratios.
To evaluate formulationsfor various quality control parameters.
Materials and methods:
7. 1 Sources and collection of data:
Reference Books.
Web resources and experimental work.
 International Journal of Pharma Tech Research.
 Journal of Pharmaceutical Research and Health Care.
Indian Journal of Pharmaceutical sciences.
AAPS PharmaSci Tech.
 Scholars Research Library.
International Journal of Pharmaceutics.
International Journal of Pharmaceutical Sciences Review and Research.
 J-Gate@ Helinet.

7.2 Method of collection of Data:
The data was collected from the prepared formulations, in vitro andevaluation and various standard books, journals & other sources like research literature data bases such as science direct etc.
A)MATERIALS :
Antiasthmatic drug - Salbutamol sulphate.
Formulation of tablet using suitable Hydrophilic and HydrophobicPolymers.
B)METHOD :
The active agent and excipients will be formulated into tablet by wet granulation technique using different polymers with different ratios along with other regular excipients.
C)EVALUATION STUDIES :
Precompression studies :
Bulk density.
Tapped density.
Carr’s index.
Angle of repose.
Hausner’s ratio.
Post compression studies :
Thickness.
Hardness.
Friability.
Weight variation.
 Content uniformity.
In vitro Dissolution studies:
The invitro drug dissolution release studies will be carried out using USP XXIV dissolution test apparatus at 100 rpm. The dissolution media consist of 900 ml of phosphate buffer (pH 6.8) and dissolution is carried out for 12 hrs. maintaining temperature at 37±0.5°C. Aliquots of 5 ml are withdrawn at 30 minutes interval and an equivalent amount of fresh dissolution media is replaced. These aliquots are filtered and absorbance of filtrate is measured in each case at 275 nm using UV spectrophometer against fresh pH 6.8 phosphate buffer solutions as blank.2
7.3Doesthis study require any investigations or interventions to be conducted on patients or animals? If so, please describe briefly.
-No.
7.4Ethical clearance :
- Not applicable.
LIST OF REFERENCES:
1.Goudanavar PS, Patil SM, Manavi FV.Design and characterisation of sustainedrelease microcapsules of Salbutamol sulphate. Int J Pharm Tech Res 2010April-June;2(2):1144-49.
2. Ghosh A, Gupta KS. Formulation development and in vitro evaluation of sustained release matrix tablets of Salbutamol sulphate. J Pharm Res Health Care;2(3):222-27.
3. Banker GS, Rhodes CT. Informa healthcare, Modern pharmaceutics, 4th edition.Drug PharmSci 2009;121:p.502-03.
4. Dandagi PM, Mastiholimath VS, Patil MB, Manvi FV, Gadad AP, Sharma R.Development and evaluation of Theophylline and Salbutamol sulphate sustainedrelease matrix tablets. Indian J Pharm Sci2005Sept-Oct;67(5):598-602.
5.Thaned P, Aroonsri P, Padungkwan C, Puttipipatkhachorn S. Effect ofpolysulfonate resins and direct compression fillers on multiple unit sustained release Dextromethorphan resinates tablets. AAPS Pharm Sci Tech 2005;6(2):E190-97.
6.Merekar AN, Godge RK, Parjane SK, Kuchekar BS, Kendre PN, Tagalpallewar PP, Dighe NS. Formulation and in vitro-in vivo evaluation of Salbutamol sulphate sustained release tablets. Sch Res Libr Der Pharm Lettre 2010;2(1):546-52.
7.Chaibva F, Burton M and Walker RB.Optimization of Salbutamol sulphate dissolution from sustained release matrix formulations using an artificial neural network. Pharm J 2010;2:182-98.
8.Solinis MA, Lugara S, Calvo B, Hernandez RM , Gascon AR, Pedraz JL. Release of Salbutamol sulphate enantiomers from hydroxypropylmethylcellulose matrices. Int J Pharm 1998;161:37-43.
9.Hernandez RM, Gascon AR, Calvo MB, Caramella C, Conte U, Dominguez GA et al., correlation of in vivo release and in vivo absorption characteristics of four Salbutamol sulphate formulations. Int J Pharm 1996;139:45-52.
10. Furlanetto S, Cirri M, Maestrelli F, Corti G, Mura P. Study of formulationvariables influencing the drug release rate from matrix tablets by experimental design. Euro J Pharm Biopharm 2006;62:77–84.
11. Bravo-Osuna, Ferrero C, Jimenez-Castellanos MR. Drug release behaviour fromMethyl methacrylate-starch matrix tablets: effect of polymer moisture content. Euro J PharmaBiopharma 2008;69:285–93.
12.Prajapti BG. Patel KR. Design and in vitro evaluation of novel Nicorandil sustained release matrix tablets on combination of hydrophilic and hydrophobicMatrix system. Int J Pharm Pharm Sci Rev Res 2010 Mar-Apr;1(1):33-38.
13.Raghavendra Rao NG, Gandhi S, Patel T.Formulation and evaluation of sustained release matrix tablets of Tramadol hydrochloride.Int J Pharm PharmSci 2009 Nov-Dec;1(1):60-70.
14.Reddy KR, Mutalik S, Reddy S. Once daily sustained release matrix tablets of
Nicorandil formulation and in vitro evaluation.AAPS PharmSciTech 2003;4(4):1-9

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9. / SIGNATURE OF THE STUDENT
10. / REMARK OF THE GUIDE
The above mentioned information and literature has been extensively investigated, verified and was found to be correct. The present study will be carried out under my supervision and guidance.
11. / 11.1 NAME AND DESIGNATION OF
THE GUIDE
11.2 SIGNATURE / PROF.A.M.GODBOLE M.Pharm.
DEPT. OF PHARMACEUTICS
SET’s COLLEGE OF PHARMACY, S.R.NAGAR, DHARWAD- 580002.
11.3 NAME AND DESIGNATION OF
CO-GUIDE
11.4 SIGNATURE / ------
11.5 HEAD OF THE DEPARTMENT
11.6 SIGNATURE / PROF. S.P.THAKKER M. Pharm.
PROFESSOR AND HEAD,
DEPT. OF PHARMACEUTICS
SET’s COLLEGE OF PHARMACY, S.R.NAGAR, DHARWAD- 580002.
12. / 12.1 REMARK OF THE PRINCIPAL
12.2 SIGNATURE / The above mentioned information is correct and I recommend the same for approval.
Dr. V. H. Kulkarni M. Pharm.Ph.D.
PROFESSOR & PRINCIPAL,
Set’sCollege of Pharmacy,
S.R.NAGAR, DHARWAD- 580002.

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