Formulation and Evaluation of Perindopril Sublingual Tablets

International Journal of Research in Pharmaceutical and Biomedical Sciences ISSN: 2229-3701The prepared tablets in all formulations possessedgood mechanical strength with sufficient hardnessin the range of 3.6 to2.8 kg/sq.cm. The tablet meanthickness was almost uniform in all formulations.The thickness varies between 3.9 to 3.8 mm.The friability varies between 0.39 to 0.33 %. Thefriability values between 1% were an indication ofgood mechanical resistance of tablets.The drug content in all formulations (F1toF4) washighly uniform and in the range of 100.87 to 98.82%.The wetting time was found to be in the range of132 sec to 45 sec. The water absorption ratio in allformulations (F1toF4) was found to be in the rangeof 55 to 27.It was observed that wetting time andwater absorption ratio increased as theconcentration of crospovidone increased. Thedisintegration time in all formulations wereobserved within fraction of second. Thedisintegration time in all formulations (F1toF4) wasfound to be in the range 237 sec to 98 sec. It wasobserved that concentration of crospovidoneincreases disintegration time not decreasedsignificantly but the formulation F4, containg 8%crospovidone as superdisintegrant showed fasterdisintegration rate as compared to otherformulations.The in-vitro dissolution studies of all formulations(F1toF4) were conducted and the results are shownin table 03.The percentage of drug release forformulation, F1 was found to be 14.88 % during2min. And maximum percentage of drug releasewas found to be 97.01% during 26 min. Thepercentage of drug release for formulation, F2 wasfound to be 20.52 % during 2min. And maximumpercentage of drug release was found to be 98.51%during 22 min. The percentage of drug release forformulation, F3 was found to be 23.13 % during2min. And maximum percentage of drug releasewas found to be 97.76 % during 26 min. Thepercentage of drug release for formulation, F4 wasfound to be 35.51% during 2min. And maximumpercentage of drug release was found to be 99.88 %during12 min .From the above studies, it wasobserved that increase in concentration ofsuperdisintegrant i.e. crospovidone, the percentageof drug release increased. Among the allformulations (F1toF4) , the best in-vitro drugrelease observed in formulation ,F4 was found tobe 99.88 %, as increase the concentration ofcrospovidone that is due to result of rapiddisintegration. During the dissolution studies, itwas observed that the tablets were initially swelledand erodible over period of time.The in-vitro drug release data of all Perindoprilsublingual tablets were subjected to goodness of fittest by linear regression analysis according to Zeroorder equation, Ist order equation, Higuchi’sequation and Krosmeyer-Peppas equation toascertain the mechanism of drug release. Theresults of linear regression analysis includingregression coefficient are presented in table04.Among the regression correlation co-efficient(R 2 ) values of Ist order equation was found to behigher, similarly among the Higuchi’s equation andKrosmeyer-Peppas equation, the (R 2 ) values ofHiguchi’s equation was found to be higher .Hencethe drug release followed the Ist order releasekinetics with diffusion mechanism.Table 1: Formulation Composition of Fast DissolvingSublingual Tablets of PerindoprilIngredients F1 F2 F3 F4Perindopril 4 4 4 4Crospovidone 4 8 12 16Sodium saccharine 10 10 10 10Mannitol 85 85 85 85Micro crystalline cellulose 91 87 83 79Talc 3 3 3 3Magnesium stearate 3 3 3 3Table 2: Weight variation, Hardness, Thickness andFriability of Perindopril sublingual tabletsFormulation codeWeightVariationHardness(kg/cm 2 )Thickness(mm)Friability(% )F1 202.15 3.1 3.9 0.29F2 200.18 2.8 3.7 0.33F3 201.86 3.5 3.8 0.35F4 199.98 3.5 3.8 0.321196Vol. 2 (3) Jul – Sep 2011www.ijrpbsonline.com

International Journal of Research in Pharmaceutical and Biomedical Sciences ISSN: 2229-3701Table 3: Water absorption ratio, Wetting time, Disintegration time and Drug content ofPerindopril sublingual tabletsFormulation code Water absorption ratioWetting time(Sec.)Disintegration time (sec) Drug contentF1 27 132 237 99.13F2 35 88 181 98.82F3 41 68 145 99.05F4 55 45 98 100.87Table 4: Regression analysis of formulations F1-F4Release KineticsS. No. FormulationKorsemeyerZero-Order First-Order HiguchiPeppas1 F 1 0.9032 0. 9834 0.9654 0.96492 F 2 0.8891 0. 8954 0.9875 0.94853 F 3 0.9110 0. 9750 0.9679 0.96364 F 4 0.9159 0. 9452 0.9863 0.9830Fig. 1: Wetting time profile of Perindopril formulations F1-F4Fig. 2: Water absorption ratio profile of Perindopril formulations F1-F4Fig. 3: Comparison of Dissolution profile of Perindopril formulations F1-F41197Vol. 2 (3) Jul – Sep 2011www.ijrpbsonline.com

International Journal of Research in Pharmaceutical and Biomedical Sciences ISSN: 2229-3701CONCLUSIONAn optimized formulation of Perindopril sublingualtablets was found and prepared in this study bydirect compression method. The best in-vitro drugrelease observed in formulation F4 was found to be99.88 % which contain the drug Perindopril andcrospovidone as superdisintegrant agent with otherexcipients. The formulation, F4 was found to bebest among all other formulations because it hasexhibited good wetting time, water absorption ratioand faster disintegration time when compared to allother formulations.ACKNOWLEDGEMENTThe author wish to give thanks to Jeypore Collegeof Pharmacy authority for providing suitableresearch work laboratory to carried out this projectwork and my deep greatness to Glenmark P.v.t.Ltd, Mumbai, india for providing PerindoprilEribumine as gift sample.REFERENCES1. Mutasem M, Rawas-Qalaji F, Estelle R,Simons and Keith J. Fast-disintegratingSublingual Tablets: Effect ofEpinephrine Loadon TabletCharacteristics. AAPS. 2006;7(2):E1-E7.2. Birudaraj R, Berner B, Sen S. Buccalpermeation of buspirone:mechanisticstudies on transport pathways. J PharmSci. 2005;94:70-78.3. Price TM, Blauer KL, Hansen M,Stanczyk F, Lobo R and Bates GW.Single-dose pharmacokinetics ofsublingual versus oral administration ofmicronized 17 bete-estradiol. ObstGyn.1997;89:340-345.4. The Merck Index; Thirteenth edition; p;1286.5. Todd PA and Fitton A. Perindopril: areview of its pharmacological propertiesand therapeutic use in cardiovasculardisorders. Drugs. 1991;42:90-114.6. Doyle AE. Angiotensin-convertingenzyme (ACE) inhibition: benefits beyondblood pressure control. Am J Med.1992;92(4b):IS-107S.7. Hurst M and Jarvis B. Perindopril; anupdated review of its use in hypertension.Drugs. 2001;61:867-896.8. Rameshwari S and JeyaAnandi J.Formulation and evaluation of NifedipineVol. 2 (3) Jul – Sep 2011www.ijrpbsonline.comsublingual tablets. Asian J Pharm ClinRes. 2009;2(3):41-48.9. Allen LV. Rapid dissolve technology; aninterview with loyd v.allen. J Pharm Tech.2003;7:449-450.10. Lachman L, Liberman A and King JL.Tablets: The theory and practice ofindustrial pharmacy, (3 rd edition),Varghese publishing house.1987:296-300.11. Sanada H, Yonezawa Y and Danjo K.Preparation and evaluation of compressedtablet rapidly disintegrating in the oralcavity. Chem Pharm Bull. 1996;44:2121-2127.12. Edmund J. Preparation, characterizationand scale of ketoconazole with enhanceddissolution and bioavailability. Drug DevInd Pharm. 2007;33:755-765.13. Lazarus J and Copper J. Influence ofshape factors on kinetics of drug releasefrom matrix tablets. J Pharm Sci.1961;50:715.14. Gibaldi M and Feldman S. Preparation invitro evaluation of controlled release dosesform of indomethacine. J Pharm Sci.1967;56:1268.15. Higuchi T. Mechanism of drug releasefrom an acrylic polymer wax matrixtablets. J Pharm Sci. 1961;50:874.16. Krosmeyer RW, Gurny R, Doelker EM.,Bury P and Peppas NA. Factorsinfluencing drug dissolutioncharacteristics from hydrophilic polymermatrix tablets. Int J Pharm. 1983;15:25.1198