International Journal of Pharmacology and Pharmaceutical Sciences 2016; Vol: 3, Issue: 3, 14-18. Research Article ISSN: 2394-613X FORMULATION AND EVALUATION OF FAST DISSOLVING TABLETS OF PERINDOPRIL USING NATURAL AND SYNTHETIC SUPER DISINTEGRANTS P. Sobhita Rani *, Srilakshmi N, T Neelima Rani, Singireddy Anandam Malla Reddy Pharmacy College, Maisammaguda, Dhulapally, Hyderabad (India) *Corresponding Author ABSTRACT Fast dissolving tablets are emerging trend in oral drug delivery systems and received increasing demand and popularity because of ease of administration and better patient compliance. The objective of the current study was to develop and optimize fast dissolving tablets of Perindopril which is used in the treatment of hypertension. Perindopril containing tablets were prepared by wet granulation method using natural and synthetic super disintegrants like Guar gum, Sodium starch glycolate. The tablets were evaluated for pre compression and post compression parameters. The optimized formulation i.e. F4 has short wetting time and disintegration time. The present study indicated that the amount of superdisintegrant significantly affected dependent variables like wetting time, and disintegration time. The best in-vitro drug release was found to be in F4 i.e.99.98% at the end of 30 min. KEY WORDS: Perindopril, fast dissolving tablets, super disintegrants, guar gum, sodium starch glycolate, wetting time, In-vitro release. INTRODUCTION Orally disintegrating tablets disintegrate or dissolve rapidly in the patient s mouth. They are convenient for pediatric and geriatric patients and in situations where potable liquids are not available. Oral disintegrating tablets are also called porous tablets, fast disintegrating tablets, mouth dissolving tablets. For these formulations, the small volume of saliva is usually sufficient to result in tablets disintegration in oral cavity. The medication can then be absorbed partially or entirely into the systemic circulation from blood vessels in the sublingual mucosa, or it can be swallowed as a solution to be absorbed from gastrointestinal tract. The sublingual route usually produces a faster onset of action than orally ingested tablets. 1-3 Perindopril 4-7 is an angiotensin converting enzyme inhibitor and it is used in the treatment of hypertensive and congestive cardiac failure. The bioavailability of Perindopril following oral administration is very low. It drug undergoes hepatic first pass metabolism. These tablets can be prepared by several techniques like disintegrant addition, freeze drying or lyophilization, moulding, sublimation, spray drying, mass-extrusion, direct compression, melt granulation. 8-12 In the present investigation fast dissolving tablets of perindropril were formulated using natural and synthetic super disintegrants for the treatment of hypertension. The following evaluations were done: angle of repose, bulk density, tapped density, Carr s index, Hausner s ratio, weight variation, hardness, friability, Disintegration test, drug content uniformity and invitro drug release studies. MATERIALS AND METHODS Perindropril erbumine was obtained from Fransco-Indian Pharmaceutical Ltd. Mannitol, Guar gum, Sodium starch Glycolate, Starch, Talc, Magnesium Stearate were procured from S.D. Fine Chemicals. Pvt Ltd, Mumbai, India. Formulation of Perindopril Fast Dissolving Tablets Fast dissolving tablets were prepared by wet granulation method and compressed into tablet using 6 mm punches on 8 station rotary tablet machine. It is depicted in Table 1. P. Sobhita Rani. et al..; Int. J. Pharmacol. Pharm. Sci. (2016) 3:3; 14-18. 14
Table 1: Formulation Table Ingredient (mg) F1 F2 F3 F4 F5 F6 F7 F8 Perindopril Erbumine 4 4 4 4 4 4 4 4 Mannitol 61 59 57 55 61 59 57 55 Guar gum 2 4 6 8 - - - - Sodium starch glycolate - - - - 2 4 6 8 Microcrystalline Cellulose 30 30 30 30 30 30 30 30 Magnesium.Stearate 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 Talc 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 Starch Paste q.s q.s q.s q.s q.s q.s q.s q.s Evaluation of tablets Pre-compression parameters The powder blend is evaluated for angle of repose, bulk density, tapped density, compressibility index, Hausner s ratio. 1. Bulk density (Db) 13 : It is the ratio of total mass of powder to the bulk volume of powder. It was measured by pouring the weighed powder (passed through standard sieve # 20) into a measuring cylinder and the initial volume was noted. This initial volume is called the bulk volume. From this, the bulk density is calculated according to the formula mentioned below. It expressed in g / cc and is given by: Db= M/ V 0 Where, M is the mass of powder, V 0 is the bulk volume of the powder. 2. Tapped density (Dt) 13 : It is the ratio of total mass of powder to the tapped volume of powder. The volume was measured by tapping the powder for 500 times and the tapped volume was noted. It is expressed in g/cc and is given by: Dt = M/V t Where, M is the mass of powder, V t is the tapped volume of the powder. 3. Carr s index (%) 13 : The percentage compressibility (Carr s index) was calculated as 100 times the ratio of the difference between tapped density and bulk density to the tapped density. Carr s index = 100 x Tapped density - Bulk density Tapped density 4. Angle of repose (q): It is defined as the maximum angle possible between the surface of a pile of powder and the horizontal plane. q = tan -1 (h/r) Where, q is the angle of repose h is the height and r is the radius All the precompression parameters evaluated were depicted in Table 2. Post-Compression Parameters Tablets prepared were evaluated for weight variation, friability, hardness, drug content. The results are given in Table 3. 1. Weight Variation 14 : Twenty tablets were selected at random and average weight was determined. Then individual tablets were weighed and the individual weight was compared with an average weight. The percentage deviation can be determined by using the following formula: %Deviation=100*Average weight- Individual weight/average weight P. Sobhita Rani. et al..; Int. J. Pharmacol. Pharm. Sci. (2016) 3:3; 14-18. 15
The tablet passes the test if not more than 2 tablets are outside the percentage limit and if no tablet differs by more than 2 times the percentage limit. 2. Friability 15 : Friability of the tablets was checked by using Roche Friabilator. Percent friability was calculated using the formula given below: Percent friability = Final weight Initial weight/initial weight * 100 Conventional compressed tablets that loose less than 0.5% to 1% of weight are considered acceptable. 3. Hardness 16 : Hardness or tablet crushing strength is defined as force required to break the tablet when the force generated by a coil spring is applied diametrally to the tablet. It was measured using Monsanto tablet hardness tester. All the post compression parameters evaluated were given in Table 3. 4. Disintegration time: This was performed in tablet disintegration test apparatus and the details were depicted in Table 3. 5. Wetting Time: A petri plate containing water was taken and a filter paper is kept on the petri plate and tablet is placed on the filter paper. The time taken for complete wetting of the tablet is given as wetting time. Results are depicted in Table 3. 6. Invitro Drug Release Studies: 17 The invitro release studies of the formulated tablets were carried out in ph 6.8 phosphate buffer in USP dissolution apparatus II at 37 ± 0.5 C and 50 rpm speed. Samples were collected and diluted to suitable concentration and analyzed at 215 nm by using UV Visible spectrophotometer. The results are given in Table 4. 7. Drug content: Randomly selected tablets from each formulation were finely powdered and powder equivalent to 4 mg of Perindopril was accurately weighed and transferred to 100 ml volumetric flasks containing ph 6.8 phosphate buffer. The flasks were shaken to mix the contents thoroughly and analyzed at 215nm. Results and Discussion Fast dissolving tablets of perindopril were prepared and evaluated for pre-compression and post-compression parameters. Precompression properteies were depicted in Table 2. Post-compression parameters were given in Table 3 and 4. Figure 1: Standard calibration curve Table 2: Pre compression Parameters Parameters F1 F2 F3 F4 F5 F6 F7 F8 Angle of repose 24.27 24.67 25.64 25.74 23.12 23.22 22.95 22.19 Bulk density(gm/cm 3 ) 0.262 0.260 0.254 0.245 0.250 0.231 0.225 0.223 Tapped density(gm/cm 3 ) 0.332 0.324 0.321 0.310 0.283 0.275 0.269 0.285 Carr s index 18.46 18.56 20.39 21.08 25.35 18.15 22.34 23.45 Hausner s ratio 1.32 1.32 1.37 1.32 1.32 1.28 1.31 1.35 P. Sobhita Rani. et al..; Int. J. Pharmacol. Pharm. Sci. (2016) 3:3; 14-18. 16
Table 3: Post Compression Parameters Parameter F1 F2 F3 F4 F5 F6 F7 F8 Weight variation 101±2.44 101.5±1.19 102±2.44 100.5±1.5 102±0.44 102±2.0 101.5±2.0 101.5±2.29 Friability 0.996±0.2.822±0.1.780±0.2.740±0.2.994±0.1.935±0.3.834±0.2.866±0.2 Hardness 4.5±0.3 5±0.3 5±0.2 4.5±0.3 5±0.4 4±0.2 4±0.4 4.5±0.3 Wetting time(sec) 22±0.1 16±0.2 15±0.1 12±0.2 20±0.2 18±0.1 15±0.2 12±0.2 Disintegration time(sec) 64±2.45 50±1.22 45±1.24 19±1.25 70±2.57 55±3.42 49±2.52 20±1.23 Drug content 95±0.68 96±0.77 97±0.81 99±0.12 94±0.59 96±0.44 97±0.45 99±0.64 Figure 2: % drug release vs time (F1-F4) Figure 3: % drug release vs time (F5-F8) P. Sobhita Rani. et al..; Int. J. Pharmacol. Pharm. Sci. (2016) 3:3; 14-18. 17
CONCLUSION Fast dissolving tablets of perindopril were formulated and evaluated. Perindropril erbumine was found to be an effective fast dissolving tablet by taking the natural disintegrants like Guar gum and synthetic disintegrant like sodium starch glycolate. All the formulations have been shown good flow properties along with good drug release. It is conclude that the F4 formulation showed all evaluation parameters within limit. The F4 batch is showed better onset of action. So, it is conclude that at the same concentration guar gum containing tablet showed good release of drug as compared to SSG containing tablet. It is also concluded that in future guar gum could be a better option of super disintegrating agent for fast dissolving tablet by its better swelling property. REFERENCES 1. Mutasem M, Rawas-Qalaji F, Estelle R, Simons and Keith J. Fast-disintegrating Sublingual Tablets: Effect of Epinephrine Loadon Tablet Characteristics. AAPS. 2006;7(2):E1-E7. 2. Birudaraj R, Berner B, Sen S. Buccal permeation of buspirone:mechanistic studies on transport pathways. J Pharm Sci. 2005; 94:70-78. 3. Price TM, Blauer KL, Hansen M, Stanczyk F, Lobo R and Bates GW. Single-dose pharmacokinetics of sublingual versus oral administration of micronized 17 bete-estradiol. Obst Gyn.1997; 89: 340-345. 4. The Merck Index; Thirteenth edition; p; 1286. 5. Todd PA and Fitton A. Perindopril: a review of its pharmacological properties and therapeutic use in cardiovascular disorders. Drugs. 1991; 42: 90-114. 6. Doyle AE. Angiotensin-converting enzyme (ACE) inhibition: benefits beyond blood pressure control. Am J Med. 1992; 92(4b):IS-107S. 7. Hurst M and Jarvis B. Perindopril; an updated review of its use in hypertension. Drugs. 2001;61: 867-896. 8. Seager H, Drug delivery products and Zydis fast dissolving dosage form, J. Pharm. Phamacol. 50, 1998, 375-382. 9. Kuchekar BS and Arumugam V, Indian J. Pharm. Edu., 35, 2001, 150. 10. Makino T, Yamada M and Kikuta J, Fast dissolving tablet and its production, 1993, European Patent, 0553777 A2 40. 11. Bess WS, Kulkarni N, Ambike SH, Ramsay MP., Fast dissolving orally consumable solid film containing a taste masking agent and pharmaceutically active agent at weight ratio of 1:3 to 3:1, US Patent 7067116, 2006 Jun 27. 12. Meyers GL, Battist GE, Fuisz RC, Process and apparatus for making rapidly dissolving dosage units and product Thereform.PCT Patent WC 95/34293 A1; 1995. 13. Aulton ME, Wells TI, Pharmaceutics: The science of dosage form design, Engl Churchill Livingstone; 1988. 14. Pharmacopeia of India, New Delhi: Ministry of Health and Family Welfare, Government of India, Controller of publications; 1996. 15. Lachman L, Liberman HA, Kanig JL. The Theory and Practice of Industrial Pharmacy. 3rd Edition, Mumbai. Varghese Publishing House, Hind Rajasthan Building, Dadar, 1987; 318320. 16. Bhawna Gauri, Shailendra K Singh and Dimple Chopra, Formulation And Evaluation Of Colon Targeted Oral Drug Delivery Systems For Metronidazole In Treatment Of Amoebiasis, International Journal Of Pharma And Bio Sciences, Vol 2/Issue 4/Oct Dec 2011. 17. Chandan Garg and Vikrant Saluja, Oncedaily sustainedrelease matrix tablets of metformin hydrochloride based on an enteric polymer and chitosan, J Pharm Educ Res Vol. 4, Issue No. 1, June 2013. P. Sobhita Rani. et al..; Int. J. Pharmacol. Pharm. Sci. (2016) 3:3; 14-18. 18