See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/235331715

Particle Characterization of Pre-Compressed Granules for Tablet Fabrication

using a Novel Pharmaceutical Excipient

Article · February 2013

CITATIONS READS

0 2,738

3 authors, including:

Nikhil K. Sachan Surajit Kumar Ghosh

University Grants Commission, India Dibrugarh University
69 PUBLICATIONS   607 CITATIONS    62 PUBLICATIONS   704 CITATIONS   

SEE PROFILE SEE PROFILE

Some of the authors of this publication are also working on these related projects:

Synthesis of hybrid class Phenylthiazole-1,3,5-triazine derivatives as a novel antifolate for PfDHFR-TS inhibition View project

A study of Socio-Economic Empowerment and Rural Livelihood Opportunities through Planned Tapping of Medicinal Plants as Minor Forest Produce View project

All content following this page was uploaded by Nikhil K. Sachan on 05 June 2014.

The user has requested enhancement of the downloaded file.

Indian Streams Research Journal
Volume 3, Issue.1,Feb. 2013
Available online at www.isrj.net
ISSN:-2230-7850
ORIGINAL ARTICLE

PARTICLE CHARACTERIZATION OF PRE-COMPRESSED

GRANULES FOR TABLET FABRICATION USING A NOVEL
PHARMACEUTICAL EXCIPIENT

1 2 3
SEEMA PUSHKAR , NIKHIL K SACHAN , S.K. GHOSH
1,2
University Institute of Pharmacy, C.S.J.M. University, Kanpur Uttar Pradesh
3
Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh Assam.

Abstract:

One of the most efficient processes for producing unit dose medication is the
compaction of pharmaceutical powder mixtures into tablets. The acceptability of tablets
formulations in the marketplace will be primarily determined by patient acceptance in a
class of equal therapeutic value. Therefore appropriate selection and use of components
that impact on these properties are of extreme importance. However, the pharmaceutical
excipients are required to comply with pharmacotechnical aptness and regulatory
qualifications desired and implemented for the purpose. Any potential formulation must
have to be financial viable simultaneously for business competiveness. In this
connection, granules fabricated with processed watermelon flesh as novel
multifunctional pharmaceutical excipient for tablet compression have been evaluated
for the pharmaceutical and micromeritic properties towards their potential use in
manufacturing of compressed tablets with identified trade merits. Evaluation of
granules was performed using drug content particle size analysis, angle of repose, bulk
and tapped density measurement, compressibility index, hausner's ratio and water
treatment. The particle size distribution was a normal distribution in all the batches. The
angle of repose of all batches depicts excellent flow of powder with added glidant which
was further supported by compressibility Index and Hausner's ratio. The results prove
the potential of formulated granules for successful compression.

KEYWORDS-

Granule characterization, pharmaceutical excipients, drug delivery, pharmaceutical tablets.

INTRODUCTION

Drug delivery systems play an important role in therapeutic performance of medicaments and
their commercial success, further these affect the improvement of medication compliance too. The easy
administration for the patient and the simple handling of the active drug dose makes the tablet a very
favored dosage form worldwide. In view to obtain desired properties of compacts, the usage of powder
formulations commonly consisting of one or more additives and it's quite seldom that any therapeutic active
medicament given as such in its pure chemical form. In fact the amount of excipients is many times more
that the quantity of drug itself. The Pharmaceutical excipients, therefore, have key role to play in
formulation of drug delivery systems. They can affect the overall efficiency and cost effectiveness of the
1
dosage form .Formulators apply practical understanding of pharmaceutical excipients to develop optimal,
robust formulations and the appropriate manufacturing processes. As with drug substances, excipients are
derived from natural sources or are synthesized either chemically or by other means. The International
Pharmaceutical Excipients Council defines an excipient as any substance other than the active drug or
Title : PARTICLE CHARACTERIZATION OF PRE-COMPRESSED GRANULES FOR TABLET FABRICATION USING A NOVEL
PHARMACEUTICAL EXCIPIENT Source:Indian Streams Research Journal [2230-7850] SEEMA PUSHKAR1, NIKHIL K SACHAN2,
S.K. GHOSH3 yr:2013 vol:3 iss:1
 PARTICLE CHARACTERIZATION OF PRE-COMPRESSED GRANULES FOR .....

prodrug that is included in the manufacturing process or is contained in a finished pharmaceutical dosage
form. During the past few years, industry has come to understand better, the excipient functionality and
variability as well as excipients' role in the drug-product supply chain2 . A limited choice of excipients with
all of these attributes are presently available in the market can make formulation design and challenge
selection of excipient 3 . Hence, there has always been a search for the better pharmaceutical excipients for
formulation development. Moreover, investigation of new pharmaceutical excipients is also an important
tool to overcome patent curtains and cost competitiveness 4 . Therefore presently in highly competitive and
increasingly global pharmaceutical market, when there is a mounting pressure on the research and
development (R&D), to shorten development time and get products to the market faster with a cost
effective formulation, new pharmaceutical excipients appears to be the master key at techno-scientific level
for financial planning and performance of pharmaceutical industries in developing countries5 .There has
been paradigm shift towards the utilization of various natural excipients which have previously been
consumed in some form by public so that it can be classified as GRAS (Generally Regarded as Safe) and
thereby reducing the cost and time for regulatory approvals. Moreover, the natural materials have been
extensively used in the field of drug delivery also because they are readily available, cost-effective, eco-
friendly, capable of multitude of chemical modifications, potentially degradable and compatible due to
5
their natural origin . In addition this can be a potential marketing tool in the 'herbal boom worldwide', the
present day consumer look for the natural ingredients in the food drug and cosmetics as they believe that
anything natural will be more safe and devoid of side effects as compared to their synthetic counterparts6 .
An increasing importance is the fact that plant resources are renewable and if cultivated or harvested in a
sustainable manner, they can provide a constant supply of raw material7.Hence the comprised research
work presents pharmacotechnical investigation of precompressed granules prepared for tablet fabrication
using processed flesh of Ctrullus lannatus as a novel excipient material functionally used towards tablet
disintegrant action. The Paracetamol was taken as model drug in this study.

MATERIALS AND METHODS:

Material and Instruments: Watermelon collected from open market, Poly, N-1-2-Vinyl Pyrollidone
(Merck chemicals, Mumbai, India); Calcium Carbonate, Magnesium Stearate, Talc (Central Drug House,
New Delhi, India), Maltodextrin (Hi- Media, Mumbai, India), Paracetamol was supplied by Merck
Chemicals, Mumbai, India. Hand Blender (Koryo, KHB 5011), Homogenizer (Remi India), Vertex Mixer
(SPINIX), Bulk density Apperatus (Hicon), Rotary Vacuum Evaporator (Evator Rotatory Evaporator,
Medica Instruments, Ltd, India), Spray Dryer (Custom made, Biotech Park, LKO), Refrigerator
(Samsung), Vacuum Oven (Hicon, India), Grinder (Philips), Sieve # 10 (B.P. Standard), Projection
Microscope (Olympous), Camera (Cannon), Lab. Lyophilizer (STARTEK), U.V visible spectrophoto-
meter (Shimadzu 1700), High Sensitivity Electronic Balance (KM-2, Deva Inc), USP – Tapped density
apparatus (Electrolab, India), pH meter (LI 127, Elico Ltd, India), Mechanical Stirrer (Remi, India) and
Desiccator etc.

Collection and Authentication of Fruit: Watermelon (Citrullus lanatus) fruits were purchased from fruit
and vegetable market Chakarpur and the same were confirmed with University Department of Life
Sciences. The watermelon being a well known fruit did not call for a voucher specimen to keep. Same lot of
the watermelon collected was used in all type of drying and subsequent evaluation for study.

Drying methods: The watermelon flesh taken off and blended (Koryo KHB 5011) to liquidize the pulp,
passed through sieve #10 and the strain collected was homogenized (Remi, India) and shaken in a vertex
shaker (Spinix, India) so as to obtain the desired hydro-extracted biomaterial in strain and to remove
undesired fruit parts. This blend filtered through a muslin cloth to have water soluble fraction which was
dried to powder using different drying methods viz. direct sun drying, vacuum drying, spray drying and
8
lyophilisation .
Preparation of Granules: The granules were fabricated using non-aqueous wet granulation technique
with calculated requisite quantities of the drug and additives (Table 1), mixed thoroughly in a double cone
mixer at 90 rpm for 15 min, and a sufficient volume of granulating agent (isopropyl alcohol) was added
slowly. After enough cohesiveness was obtained, the mass was sieved though # 14 standards sieve. The
granules were dried in oven at a temperature below 40°C for 30 min. re-shaped and unified through sieve #
12. Talc, magnesium stearate and aerosil were finally added as anti-adherent, lubricant and glidant9.The
granules so prepared were used for evaluation and stored in desiccators till further use for tablet
compression.

Indian Streams Research Journal • Volume 3 Issue 1 • Feb 2013 2

 PARTICLE CHARACTERIZATION OF PRE-COMPRESSED GRANULES FOR .....

Table 1: Formulation Com ponents of Granules

Act ive Medicament Paracetamo l (PCM)

Diluent M icrocrystallline Ce llulose (MCC)
Binder and Adhesive Corn Starch and PVPK-25
Test Disintegrant Spra y dried Watermelon Powder
Lubricant Stearic acid
Ant iadherent and Glidant Talc and Aerosil
Preservat ives Methyl paraben sodiu m a nd
Propyl paraben sodium

Drug Content Analysis: Accurately weighed quantity of the granules containing about 0.15 g of
Paracetamol, added to 50 ml of 0.1 M sodium hydroxide, diluted with 100 ml of water, shaken for 15
minutes and added sufficient water to produce 200.0 ml. Mixed, filtered and diluted 10.0 ml of the filtrate to
100.0 ml with water. To 10.0 ml of the resulting solution added 10 ml of 0.1 M sodium hydroxide and further
diluted to 100.0 ml with water. Mixed well, and the quantification of paracetamol was done by Measuring
the absorbance of the resulting solution at the maximum at about 257 nm through subsequent calculations
taking '715' as the specific absorbance at 257 nm10.

Granule Strength – Pinch Toughness: The mechanical strength and friability of the prepared granules
was evaluated through an empiric pinch toughness assessment which held responsible the percentage of
fines in the granulation and could also provide a clue regarding optimal binder concentration.

Particle size distribution: A sieve stack comprised 6 sieves with an aperture progression. Powder was
loaded in the coarsest sieve of the assembled stack and nest is subjected to mechanical vibration. After 10
min, the particles are considered to be retained on the sieve mesh; then weighed the powder retained in the
sieves and the respective parameters were calculated 9.

Bulk and Tapped Densities: Exactly 50 g of granules were weighed and transferred to the cylinder of Bulk
Density Apparatus (Hicon). The volume occupied by the granules recorded as the bulk volume. Tapped
volume was recorded after there was no further reduction in volume. Measurements were done
quadruplicate and average bulk and tapped volumes were recorded. Bulk and tapped densities were
11
computed as per the method given in USP General Chapters < 616> .The data generated were used in
computing the carr's index and Hausner's ratio of starch. Bulk density (LBD) and tapped density (TBD) was
calculated using the formula given below 12:

Bulk Density = Weight of the powder/ Volume of packing

Tapped Density = Weight of the powder/ Tapped Volume

Angle of repose: Angle of repose (è) was determined by fixed funnel method12 and inference drawn as
11
described under general chapters . The fixed funnel and free-standing cone method employ a funnel that is
secured with its tip at a given height, 'h' which was kept 2 cm above graph paper that was placed on a flat
horizontal surface. With 'r', being the radius of base of conical pile:

tan è = h / r thus è = tan-1 (h / r)

Indian Streams Research Journal • Volume 3 Issue 1 • Feb 2013 3

 PARTICLE CHARACTERIZATION OF PRE-COMPRESSED GRANULES FOR .....

Table: 2: Flow Properties and Corresponding Angle of Repose

Flow Property Angle of Repose (è)
Excellent 25-30
Good 31-35
Fair 36-40
Passable 41-45
Poor 46-55
Very poor 56-65
Very-very Poor > 66

Carr's Compressibility Index and Hausner's ratio: The Carr's compressibility index and Hauser's ratio
were calculated using tapped bulk density (TBD) and bulk density i.e loose bulk density (LBD) using the
formula as showed below12 :

Carr's compressibility index (%) = [(TBD-LBD) ×100/TBD]

Hausner's ratio = [TBD/LBD × 100]

Carr's compressibility index is a one point determination and serves as an empirical guide to
Flowability and consolidation behavior of a powder. It is a simple index that can be inferred through a scale
of Flowability as given below in Table 3.

Table 3: Scale of Flowability

Type of Flow Carr’s Index (%)
Excellent Flow 5 --15
Good Flow 12 --16
Fair to Passable Flow 18 --21
Poor Flow 23 --35
Very Poor Flow 33 --38
Extremely poor Flow >40

A similar index has been given by Hausner. Values less than 1.25 indicate good flow (=20% Carr's
index), while greater than 1.25 indicates poor flow (=33 % Carr's index). Between 1.25 and 1.50 added
glidant normally improves flow.

Water Treatment Test: Granules prepared with processed watermelon powder were subjected to
treatment with distilled water in a neat, clean and dry Petridis in view to assess their tendency to disperse
into GI fluid. The aquatic sample was mounted on to the stage of projection microscope for direct
observation of the granules undergoing deformational changes with time.

Indian Streams Research Journal • Volume 3 Issue 1 • Feb 2013 4

 PARTICLE CHARACTERIZATION OF PRE-COMPRESSED GRANULES FOR .....

RESULTS AND DISCUSSION:

The formulation of solid dosage forms involves processing of multiparticulate powders which are
heterogenous in shape, size and size distributions. The importance of regular flow properties of powder or
granules from the hopper to the die of the machine cannot be over emphasized. The need to ensure the free
flow properties of powders
poses a lot of challenges to
the pharmaceutical
formulator and hence
there is a desire for
pre-granulation procedure
prior to further processing.
Granulation is the process
by which powdered
particles are made to
possess cohesive qualities,
aggregate or adhere to
form regular larger sized
multiparticulate entities
called granules by the
addition of a granulating
(binding) fluid. Granulation
of drug particles is usually
carried out to impart
cohesiveness to the tablet
formulation and to improve
on the flow characteristic
properties of the
individual particles in order to improve the
inherent poor compression properties and to prevent segregation of the primarily from differences in
size or density 13-12. An important consideration which is often ignored during tablet processing is the
15
size of the particles before compaction . The goal of pharmacotechnical
characterization, therefore, is to
predict the desired formulation
parameters of the granulations
prepared for tablet fabrication
through appropriate
methodology which could assure
to a certain extent about the
suitability of powdered
components used for
formulation. The comprised
reviled the prepared granules
had normal particle size
distribution in all the batches and
ranges from 179.52±0.38 to
65.83 ± 0.48ìm. The
formulation F42 had highest
arithmetic mean diameter (ì)
and F5 found with lowest
arithmetic mean (ì) diameter. It
is tempting to think of each
particle in a granular material as a large molecule in a normal gas or liquid. This approach has problems
because it is immediately apparent that the masses of the individual particles are so large that classical
mechanics is all that is relevant to their dynamics and deformation16. Thus, the ability of an excipient to
impact and control the amplitude of its implicit property is intrinsically related to the process used to
17
generate the product .Characteristics of granulation are reported to affect a lot the properties of
compressed tablets manufactured18. A new component added or replaced in formulation may cause a
cognizable difference in attributes of granulation. It was therefore subjected to

Indian Streams Research Journal • Volume 3 Issue 1 • Feb 2013 5

 PARTICLE CHARACTERIZATION OF PRE-COMPRESSED GRANULES FOR .....

pharmaceutical evaluation for different micromeritic and physico-mechanical properties including

particle size and size distribution, flow behavior, compressibility, and densities etc which are
summarized in Table 4 for
the various batches
prepared.The granules
were also evaluated in
terms of mechanical
hardness and pinch
toughness which dictate
the resistance to friability
of the formulated granules,
compressibility and
hardness of compact
produced after compression.
The pinch toughness of the
granulation was found
dependent on the
concentration of PVP and
order of mixing.
The pinch toughness
was optimized through
experiential wisdom and PVP concentration was taken as variable for formulation
optimization in design
consideration using
Stat-Ease Design
Expert 8.4.0 software. The water treatment test depicts the dispersibility and resestance to hydrolytic
mechanical cleavage of inter-particulate bonding and demonstrates
functional capability and wicking potential of disintegrating agent used (Fig. 1-7). Particles exhibit so
many unique properties
that they could be
r e g a r d e d a s
constituting fourth stet
o f m a t t e r. W h e n
compacted they exhibit
rigidity of solid body, if
rounded in shape and
suitably graded they
will flow like liquid,
whilst the very fine size
particles in an open
system of the same
order of density behave
a s g a s . Ta b l e t
technology, however is
mainly concerned with
the particles in the solid
state, wherein
particulate materials
consist of a number of
particles which purport
dual nature, the one
fundamental properties and other derived properties; Heywood (1963) classified separately the
fundamental and derived properties of the particles defined chemical composition, molecular structure,
particle size, shape, porosity and density etc as fundamental properties while angle of repose, bulk density,
compressibility flow, adsorption behavior and segregation tendency as derived properties (Heywood
1963).The moisture present in pre-compressed granules affect qualities of final product especially the
compressibility of particles and hardness of tablet traduced. In fact, in present study granulations did not
have quantifiable moisture content being produced by non-aqueous wet granulation method adopted
because of highly hydrophilic nature of watermelon powder18.

Indian Streams Research Journal • Volume 3 Issue 1 • Feb 2013 6

 PARTICLE CHARACTERIZATION OF PRE-COMPRESSED GRANULES FOR .....

Formulations Angle of Rep ose Bulk Den sity Hausner’s Ratio Carr’s Index (%) Arithmetic Mean
(°) ± S.D (g/cc) ± S.D ± S.D ± S.D Diameter (µ) ± S.D

F1 17.26 ± 0.02 0.476 ± 0.03 1.19 ± 0.04 16.00 ± 0.01 89.72 ± 0.47
F2 17.02 ± 0.0 0.477 ± 0.04 1.16 ± 0.02 14.28 ± 0.02 146.22 ± 0.64
F3 18.25 ± 0.04 0.479 ± 0.06 1.23 ± 0.02 19.23 ± 0.04 121.68 ± 0.50
F4 17.52 ± 0.06 0.487 ± 0.05 1.23 ± 0.06 19.60 ± 0.06 151.29 ± 0.39
F5 16.58 ± 0.03 0.526 ± 0.02 1.13 ± 0.02 18.75 ± 0.05 65.83 ± 0.48
F6 21.57 ± 0.04 0.512 ± 0.03 1.21 ± 0.02 23.52 ± 0.03 163.56 ± 0.52
F7 16.29 ± 0.04 0.256 ± 0.01 1.25 ± 0.06 21.62 ± 0.02 119.80 ± 0.72
F8 18.75 ± 0.05 0.625 ± 0.03 1.21 ± 0.05 11.29 ± 0.01 155.33 ± 0.54
F9 17.46 ± 0.06 0.571 ± 0.04 1.25 ± 0.04 22.22 ± 0.04 108.56 ± 0.68
F10 18.71 ± 0.07 0.277 ± 0.06 1.25± 0.03 21.73 ± 0.03 82.97 ± 0.48
F11 18.51 ± 0.01 0.689 ± 0.06 1.23 ± 0.03 11.62 ± 0.02 197.98 ± 0.54
F12 19.25±0.25 0 .456±0.05 1.21±0.06 13.26±0.02 112.9 8±0.26
F13 17.25±1.23 0 .561±0.25 1.24±0.02 14.25±0.03 131.5 9±0.24
F14 18.25±0.36 0.59±0.26 1.15±0.05 11.26±0.08 168.3 5±0.39
F15 17.69±0.25 0 .458±0.36 1.14±0.04 20.15±0.07 157.2 6±0.27
F16 19.65±1.23 0 .436±0.45 1.23±0.07 17.56±0.07 167.0 8±0.26
F17 20.25±1.59 0 .256±0.25 1.19±0.09 17.56±0.05 154.2 6±0.13
F18 20.89±1.45 0 .248±0.46 1.11±0.02 18.12±0.04 86.26±0.45
F19 16.78±1.27 0 .268±0.78 1.25±0.04 19.24±0.01 104.5 6±0.43
F20 21.78±0.29 0 .598±1.23 1.18±0.03 14.23±0.06 97.26±0.35
F21 22.45±0.56 0 .458±0.26 1.10±0.01 11.24±0.05 68.35±0.19
F22 17.25±1.58 0 .476±1.35 1.25±0.05 14.26±0.01 115.9 7±0.16
F23 14.25±0.45 0 .248±2.36 1.21±0.06 16.25±0.06 116.8 7±0.43
F24 15.24±2.40 0 .756±0.78 1.22±0.04 18.24±0.03 92.26±0.89
F25 15.26±0.25 0 .456±0.89 1.25±0.08 18.36±0.08 145.3 5±0.75
F26 18.45±0.45 0 .489±1.74 1.16±0.04 11.59±0.09 124.3 6±0.36
F27 20.45±0.78 0 .459±1.56 1.25±0.05 18.36±0.04 113.4 5±0.48
F28 22.42±0.25 0 .364±0.45 1.25±0.06 17.89±0.06 116.4 8±0.32
F29 19.45±0.78 0 .257±0.49 1.22±0.03 18.23±0.07 128.3 5±0.31
F30 14.25±0.36 0 .459±0.85 1.12±0.05 15.24±0.01 85.96±0.29
F31 15.23±0.74 0 .459±0.73 1.16±0.06 14.56±0.03 97.86±0.24
F32 16.45±0.84 0 .789±0.72 1.25±0.01 18.24±0.04 105.3 6±0.15
F33 17.85±0.15 0 .457±1.36 1.15±0.05 15.47±0.06 111.4 5±0.19
F34 16.46±0.49 0 .526±0.91 1.18±0.09 14.56±0.07 85.26±0.35
F35 20.45±0.76 0 .604±0.14 1.25±0.04 18.69±0.02 117.8 9±0.35
F36 21.45±1.23 0 .625±1.56 1.21±0.08 19.45±0.04 123.6 4±0.45
F37 20.45±1.59 0 .548±1.27 1.19±0.07 18.24±0.06 128.3 9±0.64
F38 15.48±0.56 0 .568±1.69 1.22±0.02 18.78±0.07 134.2 6±0.62
F39 18.25±0.48 0 .412±0.36 1.12±0.05 12.34±0.03 138.4 5±0.72
F40 14.45±0.56 0 .526±0.94 1.15±0.06 14.24±0.04 145.3 7±0.25
F41 18.49±0.79 0 .479±0.73 1.16±0.04 13.45±0.08 168.4 5±0.52
F42 14.29±0.47 0 .604±0.64 1.14±0.05 14.89±0.08 179.5 2±0.38
F43 17.41±0.46 0 .607±0.63 1.25±0.03 17.46±0.09 137.2 5±0.75
F44 16.25±0.76 0 .705±0.26 1.15±0.04 15.24±0.05 112.3 6±0.84
F45 15.48±0.72 0 .736±0.38 1.17±0.06 16.24±0.04 128.6 9±0.76
F46 16.29±0.45 0 .432±0.42 1.24±0.07 17.59±0.05 137.2 6±0.34

When quantity of active medicament represents major weight of the granules, it is likely to affect derived
properties of the particles relevant for further compaction. Therefore the excipients properties suitable for
one formulation might not be similarly optimal to other formulation. This is, therefore, essential to study
and optimize the formulation along with pre-compressed particle properties in any new formulation even
though majority of the component might have been proposed to be utilized in similar proportions as
previously optimized.
The angle of repose ()

Indian Streams Research Journal • Volume 3 Issue 1 • Feb 2013 7

 PARTICLE CHARACTERIZATION OF PRE-COMPRESSED GRANULES FOR .....

is a valuable tool for

evaluation of flow
characteristics, when
moving particles fall
on one over another
then these slip to
surface under gravity
until corresponding
surface to angle of
repose is in equilibrium
and force of gravity is
mutually balanced
with inter-particulate
attraction and friction
etc. However, the
angle of repose is an
official test for tablets
as prescribed in I.P.
2007, the major
problem in its
interpretation and utilization
is that the value of
measured angle varies
according to the method
used and shape of pile gets deformed by diverging particles. Standing funnel method, official in some
compendia, valued the angle of repose for prepared granules in range of 22.45±0.56 (F21) – 14.25±0.36
(F30). All formulations
having Excellent flow
of granules (Table4),
which is significant to
uniform feed from
hopper so the
distribution of active
ingredient with all
excipients remain
equal and helps to
produce uniform
weight of tablets. The
flow behavior is
affected to a greater
extent by size and
shape of the particle
which dictates
compressibility and
segregation tendency
of particles of different
size range. Carr (1965)
suggested that it is
appropriate to assess
the compressibility and cohesiveness of particles in addition to the angle of repose and angle of spatula in
adjudicating the tendency of particles affecting the flow from hopper/feeder. Because the inter-particulate
interactions influencing the bulking properties of a powder are also the interactions that interfere with
powder flow, a comparison of the bulk and tapped densities can give a measure of the relative importance of
these interactions in a given powder. The index was devised to dictate powder flow property and used
parallel for comparison to the angle of repose. The Compressibility index and Hausner's ratio are measures
of the propensity of a powder to be compressed as described above. The pharmacotechnical properties,
interpreted considering interrelated aspects of derived properties and allied formulation factors. The
granules credit pharmaceutical fitness and owe additional merits of aesthetic appeal required in
pharmaceutical preparation owing popular fruit flavor. Moreover as suggested in literature the citrulline

Indian Streams Research Journal • Volume 3 Issue 1 • Feb 2013 8

 PARTICLE CHARACTERIZATION OF PRE-COMPRESSED GRANULES FOR .....

present is converted to an essential amino acid called arginine by a transamination reaction involving
glutamic acid and metabolically related compounds. Arginine produced is released into the renal vein after
being synthesized from citrulline, which is found to be beneficial to heart, liver and circulatory system of
21
body, and helps in improving the body's immune system .

CONCLUSIONS:

The amplitude of pharmacotechnical characterization incorporate prediction of desired

formulation parameters of the granulations prepared for tablet fabrication through appropriate
methodology towards implicit objective to assure to a certain extent about the suitability of powdered
components used for formulation especially excipients employed for ensuring efficient production of the
drug product and to improve patient acceptability and aesthetics of the final product. The results of study
have shown that the granules are appropriately formulated which can be used as such to compress tablets
for further quantitative optimization. The processed watermelon flesh seems excellent multifunctional
healthier excipient primarily a disintegrant as depicted in water treatment test simultaneously capable of
being put to use as natural antioxidant, colouring and flavouring agent.

REFERENCES:
1. Liberman, H., Lachman, Leon and Squartz, J.B. Pharmaceutical Dosage
Forms : Tablets. [Ed.] 2nd. New York : Marcel Decker Publications, 2005. Vol. 1.
2. Excipients Step into the Spotlight. Drakulish, A. 34, 2010, Pharm. Tech., Vol. 6,
pp. 34-42.
3. Bhattacharyya, L., et al. Excipients: Background/Introduction. [book auth.] A.
and Chaubal, M.V. Katdare. Excipient Development for Pharmaceutical,
biotechnology and Drug Delivery Systems. New York / London : Informa
Healthcare, 2006, pp. 1 - 2.
4. A New World of Excipients for Oral Solid Dosage Forms. Miinea, L., et al.
March 2009, Excipients Insight, pp. 1-3.
5. Kumar, Nikhil. Fabrication and Biopharmaceutical Characterization of
Microparticulate Controlled Drug Delivery System Composed of Assam Bora
Rice as Possible Mucoadhesive Backbone. Dibrugarh : Dibrugarh University,
India, 2011. Ph.D. Thesis.
6. Herbal excipients in novel drug delivery systems. Shirwaikar, A., et al. 4, 2008,
Ind J.Pharm Sci., Vol. 70, pp. 415 – 422.
7. Polymeric Material of the future based on renewable plant resources and
biotechnologies: Fibres, Film, Plastics. Perepelkin, K E. 2005, Fiber Chem, Vol.
37, pp. 417-430.
8. Pushkar, Seema, Sachan, Nikhil Kumar and Ghosh, S K. Pharmacotechnical
Assessment of Processed Watermelon Flesh as Novel Tablet Disintegrant. [book
auth.] L D Khemani, M M Srivastava and Shalini Srivatava. Chemistry of
Phytopotentials: Health, Energy and Environmental Perspectives. s.l. : Springer
Berlin Heidelberg, 2012, pp. 159-163.
9. Aulton, M E. Pharmaceutics, The science of daosage form design. s.l. : Churchill
Livingstone, 2000.
10. I.P. Indian Pharmacopoeia - 2007. 5th . New Delhi : Govt. of India, Ministry of
Health and Family Welfare, 2007. p. 903. Vol. 3.
11. USP-XXIX. United States Pharmacopeia and National Formulary (USP–NF)
General Chapter <1174> Powder Flow. Rockville : United States
Pharmacopoeial Commission, 2006.
12. Pharmaceutical Characterization and Assessment of Drug Release Behaviour of

Indian Streams Research Journal • Volume 3 Issue 1 • Feb 2013 9

 PARTICLE CHARACTERIZATION OF PRE-COMPRESSED GRANULES FOR .....

Diclofenac Sodium Extended Release Matrix Devices. Sachan, Nikhil K. and

Pushkar, Seema. 1, 2009, Int J Pharm Sci Tech, Vol. 2, pp. 14 - 21.
13. Rudnic, E.M. and Schwartz, J.D. Oral solid dosage forms. [book auth.] A.
Gennaro and R. Remington. [ed.] 20th. The Science and Practice of Pharmacy.
Philladelphia : Lippincott Williams Willkins, 2000, Vol. 1, pp. 858 - 893.
14. Norman, A.A. Tablet Manufacture. [book auth.] J. Swarbrik and J.C. Boylan.
Encyclopedia of Pharmaceutical Technology. 9th. New York : Marcel Decker Inc,
2002, Vol. 3, pp. 2713-2732.
15. Malcom, S. and Aulton, M. Granulation. [ed.] M. E. Aulton. Pharmaceutics:
The Science of Dosage Form Design. London : Harcourt Publishing Ltd, 2002,
pp. 3397 - 440.
16. Physics of the Granular State. Jaeger, H.M. and Nagel, Sidney R. 5051, March
20, 1992, Science, Vol. 255, pp. 1523 - 1531.
17. Functionality of Excipients in Medicinal Products. Parker, Andrew. 5,
September/October 2009, Chimica Oggi/ Chemistry Today, Vol. 27, pp. 5-7.
18. Effect of particle size of granules on some mechanical properties of paracetamol
tablets. Eichie, F.E. and Kudehinbu, A.O. 21, November 2, 2009, African
Journal of Biotechnology, Vol. 8, pp. 5913-5916.
19. The Evaluation of Powders. Heywood, H. 1963, Journal of Pharmacy and
P h a r m a c o l o g y, Vo l . 1 5 , p p . 5 6 T – 7 4 T. D O I : 1 0 . 1111 / j . 2 0 4 2 -
7158.1963.tb11190.x.
20. Qualifying Flow Properties of Solods. Carr, R.L. 1965, Chemical Engineering,
Vol. 72, pp. 69 - 72.
21. Lycopene content, antioxidant capacity and colour attributes of selected
watermelon (Citrullus lanatus (Thunb.) Mansfeld ) cultivars grown in India.
Nagal, Shweta, et al. 8, December 2012, International Journal of Food Sciences
and Nutrition, Vol. 63, pp. 1-5.
22. WHO Expert 46th. Committee, S.3.6. Bulk Density and Tapped Density of
Powders. 2012.
23. Kibbe, A H. Handbook of Pharmaceutical Excipient. s.l. : Pharmaceutical Press,
2000.

Indian Streams Research Journal • Volume 3 Issue 1 • Feb 2013 10

View publication stats