FORMULATION & DEVELOPMENT OF FILM COATED ... - IJPI

INTERNATIONAL JOURNAL OFRESEARCH ARTICLEPHARMACEUTICAL INNOVATIONS ISSN 2249-1031FORMULATION & DEVELOPMENT OF FILM COATED TABLETSOF ATENOLOLB.Murali Krishna * 1 , Praveen Kumar Uppala 2 , Swarna latha.M 2 , Shashidhar Reddy.R 31 Sri Venkateswara College of Pharmacy, Etcherla, Srikakulam, Andhra Pradesh2 K.V.K. College of Pharmacy, Surmaiguda, Hayathnagar, R.R.District, A.P3 T.R.R College of Pharmacy, Inole, Patancheru, Medak District, A.PABSTRACT:The aim of the present work is to develop solid oral dosage form which declines theelimination of high soluble and low permeable drugs. Atenolol is an antihypertensive drughaving High Aqueous and low lipid solubility (class III). Atenolol is a ß 1 selective antagonistworks by competing for receptor sites on β 1 receptor, located in the heart (cardiac muscle)and arterioles (smooth muscles). Atenolol is incompletely absorbed of about 50%, but mostof the absorbed dose reaches the systemic circulation. Its first pass metabolite is notsignificant hence has longer duration action. It is excreted unchanged in feces.Required formulation can be achieved by decreasing the diffusion of atenolol by using highviscosity polymers. These polymers sustain or decrease the release rate of drug and thusprevent early escape from GI tract.Key Words: Cardiac output, beta blockers, Atenolol, Diffusion.INTRODUCTION:-Hypertension or high blood pressure isa cardiac chronic medical condition inwhich the systemic arterial blood pressureis elevated. 1Hypertension is classified as:1. Primary (essential) hypertension,high blood pressure with noobvious medical cause2. Secondary hypertension, caused byother conditions that affect thekidneys, arteries, heart or endocrinesystemBeta blockers (β-blockers) or betaadrenergicblocking agents, betaadrenergicantagonists, or beta antagonists,are a class of drugs used for variousindications, but particularly for theVolume 3, Issue 3, May − June 2013management of cardiac arrhythmias,cardio protection after myocardialinfarction (heart attack), and hypertension.There are three known types of betareceptor, designated β 1 , β 2 andβ 3 receptors.‣β 1 - adrenergic receptors are locatedmainly in the heart and in thekidneys.‣β 2 - adrenergic receptors are locatedmainly in the lungs, gastrointestinaltract, liver, uterus, vascular smoothmuscle, and skeletal muscle.‣ β 3 - adrenergic receptors are locatedin fat cells.*Corresponding AuthorB.Murali Krishna90 | P a g ehttp://www.ijpi.org

INTERNATIONAL JOURNAL OFRESEARCH ARTICLEPHARMACEUTICAL INNOVATIONS ISSN 2249-1031Beta blockers inhibit this normalepinephrine-mediated sympathetic actionthat is they reduce excitement/physicalexertion on heart rate & force ofcontraction, tremor, and breakdown ofglycogen, but increase dilation of bloodvessels and constriction of bronchi 2 .The antihypertensive mechanism appearsto involve:‣ Reduction in cardiac work and acentral nervous system effect toreduce sympathetic activity‣ Antianginal effects result frommaking the heart work less andthereby reduce its demand foroxygen.‣ The anti arrhythmic effects of betablockers arise from sympatheticnervous system blockade 3 .MATERIALS AND METHODS:-Materials: Materials are shown in table-.1Method:Formulation development:Immediate release film coated tabletsprepared by wet granulation method andthe various formulas (mentioned in table2). Binders like Starch, PVPK, Gelatin,Guar gum, Hydroxy propyl methylcellulose (HPMC15000 cps) used andeffect of drug release is studied 4 . Diluentslike Lactose, Magnesium carbonate, Microcrystalline cellulose and Lubricant likeMagnesium sterate were used. All theingredients (except mg stearate and talc)were mixed uniformly, granulated usingpurified water and mesh size 16 & 22followed by addition of glidant andlubricant to the granules 5 .The prepared powder blend was evaluatedfor various parameters like bulk density,Volume 3, Issue 3, May − June 2013tapped density, angle of repose,compressibility index and Hausner ratio.After evaluation of powder blend thetablets were compressed with Rotary tabletpunching machine using 10mm punchesset. These tablets where then coated usingvarious formulations of opadry (mentionedin table 2) using pan coating technique 6 .In F1, F2, F3 Starch 1500 was used asbinder changing the concentrations ofmagnesium carbonate. In F4,microcrystalline cellulose (Avicel102)used as binder for extra granulation. In F5,maize starch is used as binder. In F6, F7,F8, maize starch is used as binder varyingthe concentrations of lactose. For F1, F3 &F4 Opadry 03B58965 where as for F2, F5,F6, F7, F8 Opadry white Y-1 7000 usedfor coating as main polymer 7,8 .Post compression parametersThese parameters were checked for bothuncoated and coated tablets.Thickness:The thickness of the tablets is determinedusing Digital Vernier callipers apparatus.Tablet hardnessThe resistance of tablets to shipping orbreakage under the conditions of storage,transportations and handling before usagedepends on its hardness. The hardness oftablet was measured by Pfizer hardnesstester. The hardness was measured interms of Kg/cm2.Weight variationTwenty tablets from each formulationwere selected randomly and averageweight was determined. Individual tabletswere then weighed and was compared withaverage weight.Friability91 | P a g ehttp://www.ijpi.org

INTERNATIONAL JOURNAL OFRESEARCH ARTICLEPHARMACEUTICAL INNOVATIONS ISSN 2249-1031Friability of the tablets was determinedusing Roche Friabilator. This devicesubjects the tablets to the combined effectof abrasion and shock in a plastic chamberrevolving at 25 rpm and dropping thetablets at a height of 6 inches in eachrevolution. Pre weighed sample of tabletswas placed in the friabilator and weresubjected to 100 revolutions.Tablets were then de‐ dusted using a softmuslin cloth and reweighed. The friability(f) is given by the formula.Friability (f) = (1 ‐ W0/ W) x 100Where„W0 ‟is weight of the tablets beforethe test and „W‟ is the weight of the tabletafter the test.In vitro disintegration timeThe disintegration time for allformulations was carried out using tabletdisintegration test apparatus. Six tabletswere placed individually in each tube ofdisintegration test apparatus and discswere placed. The phosphate buffer pH 7.2was maintained at a temperature of37°±2°C and time taken for the entiretablet to disintegrate completely wasnoted.Dissolution studies:-The study has been carried out in type IIapparatus at 50 rpm in 900 ml Acetatebuffer pH 4.5. Determine the amount ofAtenolol dissolved by employing UVabsorption at about 275 nm on Filteredportions of the solution under test incomparison with a Standard solutionhaving a known concentration of .AtenololRS prepared by dissolving an accuratelyweighed portion in a small volume ofVolume 3, Issue 3, May − June 2013methanol and diluting quantitatively withDissolution medium. An equal volume offresh medium, which was pre warmed at37⁰ C was replaced into the dissolutionmedium after each Sampling to maintainthe constant volume throughout the test.Dissolution studies were performed intriplicate.RESULTS AND DISCUSSION:The formulations were prepared by usingbinding agents like Gelatin, Guar gum,HPMC 15000cps, PVPK to control therelease rate of drug from the dosage formby Diffusion mechanism. In the F1formulation Basic Mgco 3 is used asdiluents and but the drug release was notwithin in the limit. And F2, F3formulations Heavy Mgco 3 is replaced byBasic Mgco 3 to know the release of drug.Starch is used as a Binder for first 4(F5,F6, F7, F8) formulations. And in theremaining 4 formulations Lactose is usedas Diluent and Starch along with Gelatin,Guar gum, Hpmc15000 cps are used asbinding agents to control the release rate ofthe drug. F8 formulation was betterformulation in decreasing diffusion andincreasing the permeability andbioavailability of the drugCONCLUSION:- Different formulations of Atenololtablets were prepared by usingvarious Polymers and disintegrants,binders, diluents and nonmicronized drug by wet granulationtechnique. The physical parameterssuch as weight uniformity,hardness, thickness, friability,disintegration time were evaluatedfor the tablets and found all the92 | P a g ehttp://www.ijpi.org

INTERNATIONAL JOURNAL OFRESEARCH ARTICLEPHARMACEUTICAL INNOVATIONS ISSN 2249-1031values within the specified standardvalues. From the disintegrationtime data it was found that thedisintegration time was more forthe formulation F8 which containhigh viscosity grade HPMC(Metalose 15000 cps) as binderalong with the other ingredients inthe binding fluid compared to thatfor the other formulationscontaining guar gum, gelatin,pvpk-30 and starch as binder alongwith the other ingredients in thebinding fluid 9,10 . From thedissolution profiles of the proposedtablet formulations F1 to F8 it wasfound that the drug release wasslow from the formulation F8contain high viscosity gradeHPMC (Metalose 15000 cps)compared to that from theformulations F6 and F7 whichcontains Gelatin and Guar gumrespectively. Dissolution profilesof the proposed tablet formulationF8 containing High viscosity gradeHPMC (Metalose 15000 cps) wasmatched with the dissolutionprofile of the Innovator 11 .Therefore it was concluded that F8formulation was better formulationin decreasing diffusion andincreasing the permeability andbioavailability of the drug. Stabilitystudy of the F8 was done for about1 month as per ICH guidelines andfound that the tablets are stable.Drug Release kinetics was studiedfor f8 and which follows first orderand diffusion mechanism 12 .Volume 3, Issue 3, May − June 2013REFERENCES:-1. Aulton M.E., „Granulation,Pharmaceutics, „The science ofdosage form design, ChurchillLivingstone, Edinburgh.‟ pp.187,188.2. Expert consensus document onbeta-adrenergic receptor blockersby the Task Force on Beta-Blockers of the European Societyof Cardiology.3. Heel RC, Brogden RN, SpeightTM, Avery GS. 1979. Atenolol: Areview of its Pharmacologicalproperties and therapeutic efficacyin angina pectoris andhypertension. Drugs 17:425–460.4. Ansel, Howard C, lioyd.allen Jr.and Nicholas GPopovich.Pharmaceutical dosageforms and drug delivery systems.Baltimore, Maryland: LippincottWilliams and Wilkins, 7 th edition1989.5. Banker G.S., Rhodes E.T., 1996.„Modern pharmaceutics. 3 rdedition; Marcel Dekker.‟ pp.678-721.6. Dilip M.Parikh., „Theory ofgranulation,” Hand book ofpharmaceutical granulationtechnology, Marcel Dekker.‟ INC,New York, pp.8, 15, 16,152.7. Journal of Chemical andPharmaceutical ResearchFormulation and evaluation ofValsartan film coated tablets D.Srinivas*1, Subal Debnath1, T.R.SChowdary2, S.Y. Manjunath8. Leon Lachman., HerbertA.Libermann., Joseph L. Kaning.,93 | P a g ehttp://www.ijpi.org

INTERNATIONAL JOURNAL OFRESEARCH ARTICLEPHARMACEUTICAL INNOVATIONS ISSN 2249-1031„Tablets‟, „The Theory and practiceof industrial pharmacy‟ 3 rd edition,Varghese Publication.pp.318-320,293-302,430-56.9. Martin A. solution of nonelectrolytes.In: physical pharmacy.4 ed. New Delhi: B.I. Waverly,(1993).10. Pierdomentico SD, Nicolam,Espostioaletal, Prognostic value ofdifferent indices of Bloodpressure variability in hypertensivepatients, American journal ofhypertension,22(8); p.842-7, 2000.11. The “Hand book of pharmaceuticalexcipients” fifth edition (all theexcipients Data Referred)edited by Raymond C Rowe, Paul JSheskey, Sian C Owen andpublished by Pharmaceutical Pressand American PharmacistsAssociation 2006.12. Kirch W, Gorg KG. 1982. Clinicalpharmacokinetics of atenolol. Areview. Eur J Drug MetabPharmacokin 7:81–91.Table No.1 List of MaterialsS.N Name of Materials Name of The Company1 ATENOLOL Alpha Laboratories Limited2 Lactose monohydrate (Lactochem) Sigma life sciences, Bangalore3 Basic magnesium carbonate Sigma life sciences, Bangalore4 Heavy magnesium carbonate Sigma life sciences, Bangalore5 Micro crystalline cellulose pH101 Sigma life sciences, Bangalore6 Starch Sri Krishna pharmaceuticals7 Gelatin Sri Krishna pharmaceuticals8 PVPK-30 Sri Krishna pharmaceuticals9 Hydroxy propyl methyl cellulose (15000cps) Sri Krishna pharmaceuticals10 Sodium starch glycolate Sri Krishna pharmaceuticals11 Sodium Lauryl sulfate Gluchem pharmaceuticals pvt limited12 Titanium dioxide Gluchem pharmaceuticals pvt limited13 PEG 8000 Gluchem pharmaceuticals pvt limited14 Isopropyl alcohol Gluchem pharmaceuticals pvt limited15 Dichloro methane Capricorn Pharma Limited16 Purified water Capricorn Pharma Limited17 Magnesium stearate Capricorn Pharma LimitedVolume 3, Issue 3, May − June 201394 | P a g ehttp://www.ijpi.org

INTERNATIONAL JOURNAL OFRESEARCH ARTICLEPHARMACEUTICAL INNOVATIONS ISSN 2249-1031Table No.2 composition of proposed Atenolol film coated table formulations:-S.N. Composition F1 F2 F3 F4 F5 F6 F7 F81. Atenolol 100 100 100 100 100 100 100 1002. Basic magnesium- - -carbonate 145 205.34 - 172.33. Heavymagnesium - - 205.34 - - - - -carbonate4. Avicel pH 101 - - 221.65 - - -5. Lactose - - - 172.3 172.3 172.36. Starch 1500 - 77.9 77.9 - - - -7. Maize Starch 130.65 - - 74 75 75 758. SSG - - - 8.3 - - - -Binder9 Starch 1500 30 30 30 - - - - -10 Maize starch - - - 20 60 60 60 6011 Guar gum - - - - - - 412 Gelatin - - - 4 4 - -13 PVPK-30 - - - 8.3 - - - -14 HPMC15000cps - - - - - - - 415 Sodium Lauryl 6.6 6.6 6.6 6.6 6.6 6.6 6.6sulphateExtra granulation16 Avicel pH 102 - - - 56 - - - -17 SSG - - - 16.6 - - - -Lubrication18 Magnesium stearate 2.5 1.66 2.5 4.15 3.65 3.65 3.65 3.65D. Core Tablet weight (mg) 415.5 421.05 415.5 415.5 421.5 421.5 421.5 421.5Coating materialOpadry 03B58965 15 15 15Opadry white Y-1 7000 8.5 8.5 8.5 8.5 8.5Average weight(mg) 430 430 430 430 430 430 430 430Volume 3, Issue 3, May − June 201395 | P a g ehttp://www.ijpi.org

INTERNATIONAL JOURNAL OFRESEARCH ARTICLEPHARMACEUTICAL INNOVATIONS ISSN 2249-1031Table-3 Results of Physical Evaluation of the proposed tablet formulationsS.N Physical parameter F 1 F 2 F 3 F 4 F 5 F 6 F7 F 81 Weight variation 1.65 1.42 1.54 1.18 1.35 1.44 1.23 1.482 Hardness(Kg/Square inch) 4-5 4-5 4-5 4-5 4-5 4-5 4-5 4-53 Thickness (mm) 4.5-5.24.5-5.24.5-5.2Table no.4 Comparative Dissolution Profile of F1 to F84.5-5.24.5-5.74.7-5.24.8-5.24.8-5.2Time (min) Reference F1 F2 F3 F4 F5 F6 F7 F80 0 0 0 0 0 0 0 0 05 69.6 32.7 55.6 65.4 20.9 66.2 20.34 18.05 15.610 81.9 69.5 93.1 97.9 63.6 85.6 34.5 36.12 34.220 86.9 94.1 97.6 102.5 92.2 91.1 61.2 51.35 56.830 89.7 101.3 99.2 105.1 95.3 96.1 75.65 72.36 78.545 92.1 104.2 100.3 106.5 96.7 97.7 85.05 92.50 85.260 94.2 105.1 100.7 107.8 97.9 99.1 94.56 94.36 92.1590 95 105.6 101.1 109.5 98.9 100.5 98.5 96.7 95.8120 97.6 106.2 101.1 110.3 100.9 101.3 100.1 98.50 97.84120Cumulative%drugdissolution1008060402000 50 100 150Time in minutesREFERENCEf1f2f3f4f5f6Volume 3, Issue 3, May − June 201396 | P a g ehttp://www.ijpi.org

INTERNATIONAL JOURNAL OFRESEARCH ARTICLEPHARMACEUTICAL INNOVATIONS ISSN 2249-1031Figure -1 Comparative Dissolution Profile of F1 to F8 with Reference120100Cumulative%drugdissolution80604020REFERENCEf8f700 50 100 150Time in minutesFigure-.2 Comparative Dissolution Profiles of F7 and F8 with ReferenceVolume 3, Issue 3, May − June 201397 | P a g ehttp://www.ijpi.org