World Journal of Pharmaceutical Research

Jyothi et al. World Journal of Pharmaceutical Research

SJIF Impact Factor 8.074

Volume 7, Issue 13, 912-924. Research Article ISSN 2277– 7105

FORMULATION AND EVALUATION OF FAST DISSOLVING

TABLETS OF ZIDOVUDINE USING SUBLIMATION TECHNIQUE

CH. Jyothi*, K. Akhil Kumar, M. Mamatha, N. Mamatha, G. Soujanya and

Dr. K. Hemamalini1

*Swami Vivekananda Institute of Pharmaceutical Sciences, Vangapally, Yadagirigutta,

Yadadri-Bhongir- 508286, Telangana, India.
1
Principal, Swami Vivekananda Institute of Pharmaceutical Sciences, Vangapally,
Yadagirigutta, Yadadri-Bhongir- 508286, Telangana, India.

ABSTRACT
Article Received on
14 May 2018, The aim of the present study was to formulate and evaluate the fast
Revised on 05 June 2018, dissolving tablets of Zidovudine. Zidovudine is an antiretroviral drug
Accepted on 26 June 2018,
DOI: 10.20959/wjpr201813-12681 commonly used in the treatment HIV infection. The superdisintegrants
used in this study was sodium starch glycolate and cross Carmellose
sodium by sublimation method. The tablets were evaluated for weight
*Corresponding Author
CH. Jyothi
variation, hardness, wetting time, friability, water absorption ratio and
Swami Vivekananda disintegration time and In vitro dissolution study. The tablets were
Institute of Pharmaceutical prepared by direct compression method. All tablet formulations
Sciences, Vangapally, showed quick disintegration time, which is very characteristic of fast
Yadagirigutta, Yadadri-
dissolving tablets. All the formulations showed rapid percentage drug
Bhongir- 508286,
Telangana, India.
release (28.42% - 98.51%)). The rapid drug disintegration (18 sec) was
noticed in F8 formulation when compare to other formulation,
which release 98.51% at the end of 30 minutes. The fast dissolution might be due to quick
disintegration of the tablet to form particles and rapid absorption will process
superdisintegrant was considered as the optimised formulation. The in vitro drug release
profile of the optimised formulation is F8.

KEYWORDS: Direct compression, Fast dissolving tablet, Cross Carmellose Sodium,

Sodium Starch Glycolate, Sublimation technique, Zidovudine.

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INTRODUCTION
Tablets may be defined as the solid unit dosage form of medicament or medicaments with or
without suitable diluents and prepared either by moulding by compression. It comprises a
mixture of active substance and excipients, usually in powder form, pressed or compacted
form a powder into a solid dose.[1]

Approximately one-third of the population (mainly paediatric and geriatric) has swallowing
difficulties, resulting in poor compliance with oral tablet drug therapy which leads to reduced
overall therapy effectiveness. For these reason, tablets that can rapidly dissolve or
disintegrate in the oral cavity have attracted a great deal of attention.[2]

Fast dissolving drug delivery systems were first developed in the late 1970s as an alternative
to conventional dosage forms for the paediatric and geriatric patient. These tablets are
designed to dissolve or disintegrate rapidly in the saliva generally less than 60 seconds.[3] To
fulfil these medical needs, pharmaceutical technologists have developed a novel oral dosage
forms known as orally disintegrating (dispersible) tablets (ODTs) or Fast disintegrating
(dissolving) tablets (FDTs) or mouth melting tablets (MMTs) or mouth dissolving tablets
(MDTs), immediate release tablets which disintegrate rapidly in saliva, usually in a matter of
seconds, without the need of water.[4]

Fig. 1: Schematic diagram of Mechanism of fast dissolving tablet.

Advantages of fast dissolving tablets

 No need of water to swallow the tablet.
 FDTs can be easily administered to paediatric, elderly and mentally disabled patients.
 Accurate dosing as compared to liquids.
 Dissolution and absorption of the drug is fast, offering rapid onset of action.

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Jyothi et al. World Journal of Pharmaceutical Research

 Bioavailability of drugs is increased10as some drugs are absorbed from mouth, pharynx
and oesophagus through saliva passing down into the stomach.
 Advantageous over liquid medication in terms of administration as well as transportation.
 First pass metabolism is reduced, thus offering improved bioavailability and thus reduced
dose and side effects.
 Offering improved safety.[5]

Fig. 2: Schematic diagram of Mechanism of of sublimation.

Zidovudine belongs to a class of drugs known as nucleoside reverse transcriptase inhibitors-

NRTIs. Zidovudine is used in pregnant women to prevent passing the HIV virus to the
unborn baby. This medication is also used in newborns born to mothers infected with HIV to
prevent infection in the newborns. The first effective therapy against HIV was the nucleoside
reverse transcriptase inhibitor (NRTI), Zidovudine (AZT).[6]

The aim and objective of research work is to formulate and evaluate Zidovudine fast
dissolving tablets by using superdisintegrants like sodium starch glycolate, Cross Carmellose
Sodium and Co-processed superdisintegrants by sublimation method, study the different
concentration of superdisintegrants in drug release when compared with Co-processed
superdisintegrants.

MATERIALS AND METHODS

Material
Zidovudine was gifted from Matrix Pvt Ltd Hyderabad, India. Sodium Starch Glycolate,
Cross Carmellose Sodium, Aspartame, Mannitol. Camphor, Talc, Magnesium Stearate and

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Vanillin was used as pharmaceutical ingredients were obtained from Amul Scientific, India.
The Distilled water was used obtained from Water purification unit.

Preparation of fast dissolving tablets of Zidovudine

In present investigation fast dissolving tablets of Zidovudine were prepared by direct
compression using sublimation technique. For this Zidovudine and all other excipients
according to the formula were weighed accurately. Zidovudine, Mannitol (Pearlitol SD 200),
Sodium Starch Glycolate, Cross Carmellose Sodium, Vanillin, Camphor and Aspartame were
passed through sieve # 22. All the above sieved ingredients were then mixed for 15 minutes.
Magnesium stearate and Talc previously passed through sieve # 60 was then mixed with
above blend for 5 minutes. The mixture(s) was then allowed to compress using 16 station
rotary tablet compression machines with 9.0 mm flat round punches with tablet weight 200
mg.[7]

Table 1: Formulation of fast dissolving tablets of Zidovudine (F1- F9).

Ingredient (mg) F1 F2 F3 F4 F5 F6 F7 F8 F9
Zidovudine 100 100 100 100 100 100 100 100 100
Sodium Starch Glycolate (SSG) 4 8 12 - - - - - -
Cross Carmellose Sodium (CCS) - - - 4 8 12 - - -
Co-Processed Superdisintegrant 8 16 12
- - - - - -
(CCS+ SSG) (1:1) (1:3) (2:1)
Camphor 2 2 2 2 2 2 2 2 2
Vanillin 2 2 2 2 2 2 2 2 2
Aspartame 5 5 5 5 5 5 5 5 5
Talc 6 6 6 6 6 6 6 6 6
Magnesium Stearate 3 3 3 3 3 3 3 3 3
Mannitol 78 74 70 78 74 70 74 66 70
Total wt. of each tablets 200 200 200 200 200 200 200 200 200

Preformulation studies
Selection of wavelength for analysis of Zidovudine
Accurately measured 1.0 ml of standard stock II solution was transferred into 10 ml
volumetric flask and diluted to 10 ml to give concentration of 10 μg/ml and it was used for
initial spectral scan in the UV range of 200-400 nm to detect maximum wavelength and
further dilutions for linearity were prepared from the stock solution by allegation method.[8]

Standard calibration curve of Zidovudine in pH 6.8 phosphate buffer solution

A spectrum of the working standards was obtained by scanning from 200-400 nm against the
solvent as blank to fix absorption maximum using double beam UV-Visible

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spectrophotometer. Here using pH 6.8 phosphate buffer solution for the estimation of
Zidovudine. A Standard stock solution was prepared by accurately weighed 100 mg of
Zidovudine in 100 ml of volumetric flask and dissolved in pH 6.8 PBS to obtain a
concentration 1 mg/1ml or 1000 μg/ml (Standard Stock I). Pipette out 10 ml of stock solution
- I and make up to the volume 100 ml with pH 6.8 PBS to get desired concentration of 100
μg/ml (Standard Stock II). From the stock –II solution prepared various concentrations,
Aliquots of 0.5, 1.0, 1.5, 2.0, 2.5, 3, 3.5, 4, 4.5 and 5 ml of stock solution pipette out into 100
ml standard volumetric flasks and final volume adjust up to 100 ml with simulated saliva pH
6.8 PBS to give the concentration of 5, 10, 15, 20, 25, 30, 35, 40, 45 and 50 µg/ml.[9]

Micromeritic properties
Flow properties of all batches were evaluated by measuring the angle of repose, loose bulk
density, tapped bulk density, compressibility index and Hausner’s ratio.[10]

Post-compression evaluation parameters of fast Dissolving tablets of Zidovudine

Weight variation test
I.P. procedure for uniformity of weight was followed. Twenty tablets were selected at a
random and average weight was determined. Then individual tablets were weighed and the
individual weight was compared with an average weight.[11]

Weight variation (%) = [(average weight – individual weight)/average weight] × 100

Hardness testing.
The hardness of the tablets was determined by diametric compression using Monsanto
hardness tester. A tablet hardness of about 3- 4 kg/cm2 is considered adequate for mechanical
stability.[12]

Thickness
Ten Tablets were selected randomly from individual formulations and thickness was
measured by using Verniar calliper scale, which permits accurate measurement.[13]

Friability test
The friability of the tablets was measured in a Roche Friabilator. Compressed tablets that
loose less than 0.5% to 1.0% in weight are generally considered acceptable. Ten tablets were
weighed (initial weight) and then transfer into Roche Friabilator. It was subjected to 100
revolutions in 4 min. The tablets were dedusted and reweighed (final weight). These two

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weights were applied to following formula and friability was calculated. The weight loss
should not be more than 1%.[14]

% Friability=W0/W*100

RESULTS AND DISCUSSION

Determination of absorption maximum of Zidovudine
From the UV Spectrophotometric analysis, it was conclude that the drug, Zidovudine showed
a λmax at 293 nm. Therefore the observed λmax was used for further work to analyse the test
sample.

Standards graph of Zidovudine in PH 6.8 phosphate buffer

The solution obeyed Beer’s Lambert’s law over a concentration range of 5-50 µg/ml with a
regression co-efficient of 0.993. This standard curve was used further to estimate Zidovudine
in the in vitro studies. The absorbance measures at 293 nm in UV Spectrophotometer against
reagent blank with simulated saliva pH 6.8 PBS.

Table 2: Data of standard calibration curve of Zidovudine in pH 6.8 PBS.

Sl. No. Concentration (µg/ml) Absorbance at 293 nm
1 5 0.061
2 10 0.094
3 15 0.117
4 20 0.145
5 25 0.200
6 30 0.218
7 35 0.264
8 40 0.287
9 45 0.333
10 50 0.369

Fig. 3: Standard calibration curve of Zidovudine in pH 6.8 PBS.

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Table 3: Pre compression parameters of formulation F1-F9.

Formulation Angle of Loose bulk Tapped bulk Carr’ index Hausner’s
code repose (Ɵ) density (gm/cm3) density (gm/cm3) (%) ratio
F1 25.17 0.35 0.42 16.67 1.2
F2 23.26 0.37 0.46 19.56 1.24
F3 25.17 0.41 0.51 19.60 1.24
F4 25.17 0.35 0.42 16.66 1.2
F5 25.64 0.38 0.46 17.39 1.21
F6 25.17 0.37 0.45 17.55 1.22
F7 25.17 0.38 0.44 14.22 1.18
F8 22.3 0.36 0.45 18.18 1.22
F9 23.26 0.37 0.45 17.77 1.22

Micromeritic properties
Flow properties of batches were evaluated by measuring the angle of repose and
compressibility index. In the evaluation of flowability of dry solid, the substances shows
excellent flowability of performance, when the angle of repose have the value less than 25º
17´while when compressibility index has value below 14.22 %, Hausner’s ratio was below
1.24, no aid is needed for enhancing the flowability of power. Thus, angle of repose and
compressibility index are indicates of good flowability of power blend, showing no need for
addition of glidant to enhance flowability. The better flows properties of power blend indicate
that the mixture of power produced were non-aggregated. The micromeritic properties of
powder blend is shown in table 3.

Table 4: Post compression parameters of Zidovudine tablets from F1-F9.

Hardness Friability Thickness
Formulation code Weight Variation (mg)
(kg /cm2) (%) (mm)
F1 Passes 4.2 0.52 4.26
F2 Passes 4.3 0.53 4.28
F3 Passes 4.4 0.52 4.42
F4 Passes 4.3 0.53 4.42
F5 Passes 4.2 0.62 4.36
F6 Passes 4.5 0.61 4.38
F7 Passes 4.0 0.52 4.35
F8 Passes 4.2 0.52 4.32
F9 Passes 4.2 0.51 4.29

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Table 5: Wetting time, Water absorption ratio and in vitro disintegration time.
Formulation Wetting time Water absorption In vitro disintegration time
code (Sec) ratio (%) (Sec)
F1 16 20 30
F2 15 30 26
F3 11 20 25
F4 18 40 28
F5 14 20 23
F6 12 30 21
F7 15 40 25
F8 10 50 18
F9 12 40 20

Wetting Time
Wetting time is closely related to the inner structure of the tablet, these are less wetting time
for batch F8. Due to high concentration of Cross Carmellose sodium than sodium starch
glycolate. The results of wetting time are shown in table.

In-vitro Disintegration Test

In-vitro disintegration time was measured using disintegration test apparatus. Randomly six
tablets were selected from each batch for disintegration test. Disintegration test was
performed in 900 ml phosphate buffer pH 6.8 at 30 ± 2°C. which was determine as per Indian
pharmacopeia specification for all developed formulations. Formulation F8 showed rapid
disintegration (18 Sec). Compare to other formulation due to higher concentration of Cross
Carmellose Sodium (1:3 ratio of SSG: CCS). The highest disintegration time batch F1 & F4
(Low concentration of SSG and CCS Respectively).

Water absorption ratio

Water absorption ratio which is important criteria for understanding the capacity of
disintegrates to swell in presence of little amount of water, was calculated. It was found to be
in the range of 10 – 50% seconds. The values of water absorption ratio shown in table.

The formulation prepared by direct compression method formulation containing individual

superdisintegrants shows lower water absorption ratio when compare to formulation
containing high concentration of cross Carmellose sodium than sodium starch glycolate. The
water absorption ratio also decreases due to less swelling property.

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Fig. 4: Schematic representation of Wetting time (Sec).

Fig. 5: Water absorption ratio of Zidovudine tablets.

Fig. 6: In vitro disintegration time of Zidovudine Tablets.

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Table 6: In vitro drug release data for F1-F9.

Time F1 F2 F3 F4 F5 F6 F7 F8 F9
(min) (%) (%) (%) (%) (%) (%) (%) (%) (%)
0 0 0 0 0 0 0 0 0 0
5 28.42 32.2 41.24 30.09 33.08 39.09 43.21 68.21 50.21
10 38.42 40.4 43.56 42.31 46.17 49.51 58.31 72.21 62.45
15 42.26 46.2 50.23 44.37 49.51 52.23 63.11 80.21 65.36
20 45.45 50.56 52.54 48.37 52.38 58.38 72.61 82.34 78.48
25 50.41 55.06 58.76 52.88 60.18 64.61 76.93 85.34 86.34
30 65.52 68.04 70.002 68.85 72.85 78.31 88.31 98.51 92.51

Fig. 7: In vitro drug release of Zidovudine fast dissolving tablets (F1-F3).

Fig. 8: In vitro drug release of Zidovudine fast dissolving tablets (F4-F6).

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Fig. 9: In vitro drug release of Zidovudine fast dissolving tablets (F7-F9).

In vitro drug release study

All the formulations were subject for in vitro dissolution studies tablets dissolution tester
USP XXIII. The dissolution medium PH 6.8 PBS were used to study the drug release. The
samples were withdrawn at different intervals of time and analysed at 293 nm using UV
spectrophotometer. Percentage drug release was calculated on the basis of average amount of
Zidovudine present in the respective formulation. The data obtained in the in- vitro release of
pure drug and formulations prepared by sublimation technique are tabulated in the table no.6.
The plots of percentage of Zidovudine related as a function of time (t) for formulation
prepared by sublimation technique (F1-F9) are shown in the figure. The percentage of drug
release from conventional tablets is shown in Fig.7, 8 and 9. All the formulation showed
rapid % drug release (28.42% - 98.51%) in the dissolution medium of pH 6.8 phosphate
buffer solution. a faster disintegration time could lead to an enhancement of rate of
dissolution, except formulations F1, which showed only between 28.42% - 65.52% drug
release respectively due to inadequate amount of superdisintegrant. But the greater drug
dissolution was noticed in F8 formulations in pH 6.8 PBS, 98.51% as compared to other
formulation respectively at the end of 30 min. Low percentage of drugs release of Zidovudine
in pH 6.8 PBS for batch F1. The fast dissolution might be due to quick disintegration of the
tablets to form particles and rapid absorption will take place. From the overall observations,
formulation F8 containing low concentration of SSG and high concentration of CCS
considered as the optimizing formulation, which release up 98.51% of the drug in 30 min.

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CONCLUSION
In present studies, it may be conclude that the fast dissolving tablets of Zidovudine can be
prepared by direct compression using superdisintegrants by sublimation technique. Among
all the formulations (F1-F9) the F8 formulation was found to be the best formulation in which
combinations of superdisintegrants (SSG & Cross Carmellose Sodium was used in 1:3
proportion (4%, 12%). This formulation showed the least disintegration time of 18 sec and
the highest release of more than 98.51% of drug in 30 min. The prepared tablets disintegrate
within few seconds without need of water; thereby enhance the patient compliance and the
absorption leading to its increased bioavailability. Direct compression technique would be an
effective and simple alternative approach compared with the use of more expensive process
and adjuvant in the formulation of oral disintegrating tablets. From the characterization of
oral dispersible tablets of Zidovudine it can be concluded that formulation containing Cross
Carmellose sodium 12% and SSG 4% is optimised formulation.

ACKNOWLEDGEMENT
We express our sincere thanks to Matrix Pvt Ltd Hyderabad, India. for providing gift sample
of drug. We also express our gratitude to the Principal, Management of Swami Vivekananda
Institute of Pharmaceutical Sciences, Vangapally, Yadagirigutta, Yadadri-Bhuvanagiri-
508286, Telangana, India, for providing all facilities during the study.

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