International Journal of Pharmacology and Pharmaceutical Sciences 2016; Vol: 3, Issue: 3, 14-18
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)
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
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
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
Sodium starch glycolate
Microcrystalline Cellulose 30
1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5
1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5
Evaluation of tablets
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:
Where, M is the mass of powder,
V0 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:
Where, M is the mass of powder,
Vt 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
4. Angle of repose (q): It is defined as the maximum angle possible between the surface of a pile of powder and the horizontal
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.
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
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. Pre-
compression 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
24.27 24.67 25.64 25.74 23.12 23.22 22.95 22.19
0.262 0.260 0.254 0.245 0.250 0.231 0.225 0.223
Tapped density(gm/cm3) 0.332 0.324 0.321 0.310 0.283 0.275 0.269 0.285
18.46 18.56 20.39 21.08 25.35 18.15 22.34 23.45
P. Sobhita Rani. et al.; Int. J. Pharmacol. Pharm. Sci. (2016) 3:3; 14-18. 16
Table 3: Post Compression Parameters
101.5±1.19 102±2.44 100.5±1.5 102±0.44 102±2.0
Disintegration time(sec) 64±2.45
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
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
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;
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;
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;
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 –
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
Henryka Lesniewska Préface du Dr Bernard Croisile à la maladie Prévenir, surmonter, ralentir Faire face à la maladie BAT2.indd 1 À mon ami Bernard Blache, pour avoir corrigé patiemment mes erreurs de français et pour ses idées créatives. Au docteur Philippe Barboux, chef du service de gériatrie au CH d'Arpajon, qui m'a fait confiance et m'a permis d'explorer
MD Research News Monday July 4 , 2011 This free weekly bulletin lists the latest published research articles on macular degeneration (MD) as indexed in the NCBI, PubMed (Medline) and Entrez (GenBank) databases. These articles were identified by a search using the key term "macular degeneration". If you have not already subscribed, please email Rob Cummins at [email protected]m.au with ‘Subscribe to MD Research News' in the subject line, and your name and address in the body of the email.