ISSN: 2320 - 4230
Journal of Drug Discovery and Therapeutics
Available Online at www.jddt.in
CODEN: - JDDTBP (Source: - American Chemical Society) Research Article
Volume 3, Issue 32, September, 2015, 04-08
FORMULATION DEVELOPMENT AND CHARACTERIZATION OF FAST DISSOLVING
ACETAMINOPHEN TABLETS
Abhishek Pandey*1 Bhagat Singh Jaiswal2, Manoj Sharma3
1, 2, 3
School of studies in Pharmaceutical Sciences, Jiwaji University, Gwalior (M.P.)
Received 27 July 2015; Accepted 20 August 2015
ABSTRACT
The aim of the present work is to formulate a tablet which disintegrate and dissolve rapidly and give its rapid onset of
action. Acetaminophen is an analgesic, antipyretic drug having bitter taste. In present study an attempt had been made
to formulate rapidly disintegrating tablets of acetaminophen with altered taste by using directly compressible grade
excipients which makes the formulation directly compressible with adequate mechanical strength and various
superdisintigrants like Crospovidone, Sodium starch glycolate, Croscarmellose sodium along with incorporating
sweetening agent. The tablets were evaluated for weight variation, hardness, friability, disintegration time, wetting
time, in vitro dissolution studies and drug content. It was concluded that the batch prepared by using combination of
Crospovidone and Sodium starch glycolate superdisintigrants shows excellent disintegration time, enhance dissolution
rate, taste masking.
KEYWORDS: Acetaminophen, Fast dissolving tablet (FDT), Superdisintigrants, Direct compression
INTRODUCTION: bedridden or developmentally disabled patients. Patients
Pharmaceutical technology have presented various with persistent nausea, who are traveling, or who have
dosage form alternatives for patients compliance who little or no access to water are also good candidates for
may have difficulty in swallowing solid dosage forms, FDT3. The ease of administration of fast dissolving
particularly pediatric and geriatric patients, who are in /disintegrating tablet, along with its pleasant taste, may
their old age, have difficulty swallowing or chewing solid encourage a patient to adhere to a daily medication
dosage forms1. Solid dosage forms like tablets, capsules regimen. Although a FDT may not solve all compliance
are the most popular form among all the other dosage issues, it may be enough of an advance to be of
forms because of its convenience of compactness, easy therapeutic significance4. Acetaminophen used as an
manufacturing and self-administration. A fast dissolving analgesic and antipyretic having bitter taste. The
drug delivery system can be defined as a dosage form for Acetaminophen well absorbed orally only about 1/3 is
oral administration, which when placed in mouth, rapidly protein bound in plasma and uniformly distributed in the
disintegrates or dissolves and can be swallowed in the body plasma half-life is 2-3 hrs. Acetaminophen is not
form of liquid2. It is difficult to swallow tablets as well as ordinarily amenable to tablet because acetaminophen
hard gelatin capsules and also when water is not available crystals are very hard and brittle fracture very easily
in the case of motion sickness, allergic attacks of when compressed producing capping and laminating
coughing during the common cold and bronchitis. For compacts5. In this study the formulation of fast dissolving
these reasons tablets which rapidly dissolve or tablets of acetaminophen was developed by using
disintegrate in the oral cavity play an important role and directly compressible grade excipients different
are called fast dissolving tablets. FDTs are not formulated superdisintigrants and their combination by using direct
for people who have swallowing difficulties, but also ideal compression technique.
for active people. Fast dissolving tablets are also called as
MATERIAL AND METHODS:
mouth dissolving tablets, melt-in-mouth. The target
populations for these new fast-dissolving/disintegrating MATERIAL:
dosage forms have generally been pediatric, geriatric, and
4
*Corresponding author: Abhishek Pandey |E-mail: pandey_phama@yahoo.co.in
Abhishek Pandey, et. al. / Journal of Drug Discovery and Therapeutics
Acetaminophen, Crospovidone (PPXL), Sodium starch Firstly, the graduated cylinder was tare to zero, certain
glycolate, Croscarmellose sodium (Ac-Di-Sol), Mannitol, quantity of powder (W) was carefully poured into the
Microcrystalline cellulose (PH102), Magnesium stearate, graduated cylinder and the same was weighed. Also, the
Talc, Aspartame, Peppermint flavor from Loba Chem. All volume (V0) was noted. The graduated cylinder was then
reagents are of analytical grade. closed with lid and set into the density determination
apparatus (Bulk density apparatus, Campbell electronics).
METHODS:
The density apparatus was set for 350 taps and after that
Pre formulation studies:
the volume (Vf) was determined. The Bulk Density,
Drug - Excipients compatibility study: Tapped density was calculated using the following
The study was designed to determine compatibility of formulas:
drug with different excipients. These studies were carried Bulk Density = W/V0
out in glass vials stoppers with LDPE (Low density Tapped density = W/Vf
polyethylene) plugs. API was mixed with different Where W = Weight of powder, V0 = Initial volume,
excipients & kept at storage condition 400C at 75%RH for Vf =Final volume
time interval of 1 week, 2 weeks, and 3 weeks. Compressibility Index:
Physical evaluation of blend: The compressibility index is determined by measuring
Physical Characterization of blend was done for Particle both bulk density and the tapped density of a powder 6.
size distribution, Bulk Density, Tapped density and Compressibility Index (%)
compressibility index. = Tapped density – Bulk density X 100
Particle size distribution: Tapped density
Particle size distribution of the blend was done in Formulation of tablets by direct compression method:
electronic sifter; About 20 gm. of the blend was weigh Weigh all the ingredients accurately and pass through
and added to sieve # 150, # 85, # 60, and # 36, with sieve # 40. Mix all the ingredients geometrically except
subsequent weighing of the blend in between. Time of Magnesium stearate. Then lubricate the blend with
sifting with each mentioned sieve was 2 min. / sieve. Magnesium stearate. Tablets were compressed using
Determination of Bulk Density, Tapped density and single punch tablet machine.
compressibility index:
Table 1 Illustrate the formulation design of tablet
Tablet composition
B1 B2 B3 B4 B5 B6
(mg)
Acetaminophen 325 325 325 325 325 325
Crospovidone 6 - - 6 6 -
Croscarmellose
- 5 - 5 - 5
sodium (AC-DI-SOL)
Sodium starch
- - 10 - 10 10
glycolate
Mannitol 112 121 116 115 110 111
Dibasic
20 - - - - -
calcium phosphate
Microcrystalline
- 12 12 12 12 12
cellulose (PH 101)
Magnesium stearate 3 3 3 3 3 3
Talc 4 4 4 4 4 4
Aspartame 3 3 3 3 3 3
peppermint flavor 2 2 2 2 2 2
Total 475 475 475 475 475 475
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Abhishek Pandey, et. al. / Journal of Drug Discovery and Therapeutics
EVALUATION OF TABLETS: dissolution medium. Temperature of the dissolution
Weight variation: medium was maintained at 37±0.5°c. Aliquots of
Twenty tablets were randomly selected from each dissolution medium were withdrawn at specific time
formulation and average was determined. Then individual interval and it was filtered. Absorbance of filtered
tablet were weighed and individual was compared with solution was determined by Spectrophotometer at 249
average weight8. nm and drug concentration was determined from
Friability: standard calibration curve. The dissolution rate studies
The friability of tablets was determined using friability for all designed formulations were done as presented in
test apparatus About 6 tablets (W initial) were transferred table 2 and shown in fig.1
into friability test apparatus. The apparatus was operated Determination of drug content:
at 25 rpm for 4 minutes or 100 revolutions. The tablets 20 tablets was taken and powdered accurately. Powdered
were weighed again (W final) 6. The percentage friability containing about 325 mg of acetaminophen was taken
was calculated by using following formula and shake it with 60ml methanol in 200ml volumetric
flask and dilute to volume with methanol. 5ml of this
W initial – W final solution was taken and diluted up to 100ml with
F= -------------------× 100 methanol and absorbance was noted at 249 nm7.
W initial RESULTS AND DISCUSSION:
Hardness: The compositions of different batches are described in
The hardness of the tablets was determined using Pfizer table 1. The pre formulation studies and evaluation
hardness tester Ten tablets were randomly selected from parameters like weight variation, friability, hardness,
each formulation and hardness of the same was thickness, disintegration time, wetting time, dissolution
determined .The results are expressed in average value 6. rate and assay for drug content were found to be
Thickness: satisfactory and results were presented in table 2 and 3.
Twenty tablets were randomly selected from The formulation containing crospovidone and sodium
formulations and thickness was measured individually by starch glycolate shows sufficiently decrease in disinteg-
Vernier caliper. It was expressed in millimeter and gration time (i.e. 30 sec.) among all the formulation.
average was calculated 6. When crospovidone, sodium starch glycolate, croscarme-
Disintegration test: llose sodium was used alone in the formulations,
The disintegration time of the fast dissolving tablets was disintegration time was noticed more than 1min.
determined using Disintegration test apparatus. The furthermore, when combination of superdisintigrants
operation was performed on 6 tablets in triplicate6. was used, significant decrease in a disintegration time
Wetting time: was achieved. In vitro dissolution rate study shows that
Five circular tissue papers of 10 cm diameter are placed after 10 min formulation B4 – B6 % drug release 90.27%,
in a Petri dish with a 10 cm diameter. Ten millimeters of 94.98%, 97.76% respectively. Drug content studies were
water-containing Eosin, a water-soluble dye, is added to done on selected batches and results are presented in
Petri dish. A tablet is carefully placed on the surface of table 4 which shows that the drug content are within
the tissue paper. The time required for water to reach limit. As fast dissolution formulation B5 shows
upper surface of the tablet is noted as a wetting time 8. satisfactory % drug release and disintegrating time as
In-vitro dissolution rate study: shown in fig. 1 and 2. Thus the formulation batch B5 can
In-vitro dissolution rate study was done by using USP be said as best combination of superdisintigrants for fast
Type I apparatus which was rotated at 150 rpm. dissolving tablet of acetaminophen.
Phosphate buffer pH 7.2 (900 ml) was taken as
Table 2: Pre formulation studies of Blends
Parameters B1 B2 B3 B4 B5 B6
Bulk density(g/ml) 0.62 0.52 0.58 0.51 0.61 0.58
Tapped density(g/ml) 0.62 0.62 0.61 0.63 0.62 0.58
Compressibility index (%) 16.1 19.4 16.4 20.6 19.4 20.5
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Abhishek Pandey, et. al. / Journal of Drug Discovery and Therapeutics
Table 3: Evaluation of fast dissolving tablets of acetaminophen of different batches
Parameter B1 B2 B3 B4 B5 B6
% weight variation 1.7 2.1 2.0 2.1 1.5 2.1
Thickness(mm) 3.76 3.60 3.66 3.72 3.70 3.81
Friability (%) 0.94 0.66 0.78 0.77 0.72 0.85
Disintegration Time(sec.) 74 67 72 43 30 47
Hardness (kp) 4.0 4.6 4.60 4.40 4.21 4.30
Wetting time (sec.) 70 75 62 66 58 49
Fig 1: Disintegration time (min.) of various batches containing different superdisintigrants
Fig. 2: Comparative study of % drug release of FDT of acetaminophen
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Abhishek Pandey, et. al. / Journal of Drug Discovery and Therapeutics
Table 4: Drug content studies of fast dissolving tablets of acetaminophen
Batch No. Assay (%)
B4 94.35
B5 97.21
B6 98.00
CONCLUSION: REFERENCES:
The present investigation revealed that fast dissolving 1. Subramanayam CVS. Text book of Physical
tablet with altered taste of acetaminophen can be Pharmaceutics. In Vitro dissolution. Vallabh
formulated by using direct compression method by Prakashan, 2nd edition; 2001; 235-237.
incorporating directly compressible grade excipients 2. Brown D, Drug Delivery Tech., 2004.
along with suitable superdisintigrants Crospovidone 3. Chang, R.K, Guo X., Burnside B. Couch, R. Fast-
Sodium starch glycolate. directly compressible grade dissolving tablets. Pharm. Tech. 2000; 24:52-58.
excipients makes the formulation compressible and avoid 4. Habib W, Khankaric R, Hontz J. Crit. Rev. Ther.
the capping and lamination of acetaminophen with Drug Carrier Syst. (2000); 17: 61.
adequate mechanical strength while combination of 5. Klans F. Analytical profile of drugs substances.
Crospovidone, Sodium starch glycolate in different Elsevier Publication. 2005; 269-295.
concentration enables the formulation fast dissolving 6. Fiese E F, Hagen TA, Lachman L, Liberman H.A,
simultaneously addition of sweetening agent mannitol Karnig J.L. The theory and practice of a industrial
and aspartame alter the bitter taste of drug. The ,3rd edition, Varghese publishing house, Mumbai,
proposed fast dissolving formulations exhibit satisfactory 1987; 183.
characteristics of disintegration time and enhanced 7. Siladitya B, UV-Visible spectrophotometric
dissolution and thus provide ease of patient compliance method development and validation of assay of
compare to conventional formulation of acetaminophen. Acetaminophen tablet formulation. J Anal Bio
anal Techniques. 2012; 3:6.
8. Indian Pharmacopoeia Vol. II, published by
Controller of publications, Government of India,
Ministry of Health and family welfare, Delhi,
(2007); 1020.
