Beruflich Dokumente
Kultur Dokumente
Received on 27 April, 2011; received in revised form 25 September, 2011; accepted 29 September, 2011
HECKEL AND KAWAKITA ANALYSES OF GRANULES OF THE CRUDE LEAVES EXTRACT OF VERNONIA GALAMENSIS
PREPARED USING GELATIN AS BINDER
ABSTRACT
Keywords: The powdered leaf of Vernonia galamensis (Asteraceae) is a herbal drug used
Compressibility, in the treatment of diabetes mellitus in folk medicine in northern Nigeria.
Heckel equation, The crude aqueous extract of the leaves is deliquescent and usually stored in
Kawakita equation, airtight desiccators. Efforts to use common diluents such as lactose, starch,
Gelatin,
and magnesium carbonate for tablet formulation of the extract produced
Diluents
tablets with defects such as sticking and picking. The purpose of this
Correspondence to Author:
study was to use the Heckel and Kawakita equations to investigate the
Musa Autamashih compressibility of the granules of the deliquescent crude extract of Vernonia
galamensis prepared using gelatin a universally accepted pharmaceutical
Department of Pharmaceutics and
Pharmaceutical Microbiology, Faculty of
binder and selected efflorescent pharmaceutical diluents namely; Aerosil
Pharmaceutical Sciences, Ahmadu Bello 200, Avicel PH 103 and calcium phosphate. The Kawakita model provided an
University, Zaria, Nigeria excellent fit having higher R2 values than the Heckel model. The very low PK
values of the Kawakita (indicating good fluidity) for all the different
formulations made it preferable in explaining the compressibility of granules
of the extract. The ranking for good compressibility based on the diluent type
using gelatin as binder was as follows; calcium phosphate > aerosil 200 >
Avicel PH 103.
INTRODUCTION: In folk medicine, herbal drugs are This necessitates the need for standardization and
usually prepared in form o extracts and solution by formulation of the medicines in conformity with
1
maceration, extraction and decoction techniques . current Good Manufacturing Practice (GMP). Some
Oral communication with traditional herbalists in researchers have chosen the tablet over other dosage
northern Nigeria revealed the decoction of leaves of forms for the formulation of medicinal plant extracts 2
Vernonia galamensis (Asteraceae) have been used in due to the advantages of the former. Most plant
folk medicine for ages in the treatment of diabetes extracts are hygroscopic and susceptibility to microbial
mellitus. The dry powdered leaves of Vernonia degradation, so the choice of a suitable pharmaceutical
galamensis (Asteraceae) have been used by traditional dosage form that will conform to current GMP cannot
herbalists in northern Nigeria for ages in the treatment be overemphasized. Tablets are by far the most
of diabetes mellitus. Folkloric medicines however, have frequently used dosage form for all active medicinal
neither standard dose nor acceptable method of ingredients; they have advantages for both
formulation 1. manufacturer and user.
Ease of administration, convenience of administration, portion of the graph, reflects the reduction in porosity
and accurate dosing make tablets a versatile and or the resistance to volume reduction of granules and
popular dosage form 3. A is a constant. The yield pressure, PY, is usually
calculated as the reciprocal of the linear portion of the
The purpose of this study was to use the Heckel and slope of the Heckel plot. The relative density DA was
Kawakita equations to investigate the consolidation calculated from the intercept, A, using the equation:
behavior of granules of the dry crude leaf extract of
Vernonia galamensis (EVG) prepared using gelatin DA = 1eA .. (2)
(GLT) a universally accepted pharmaceutical binder
and selected efflorescent pharmaceutical diluents DB, the relative density during the rearrangement
namely; Aerosil 200 (AR), Avicel PH 101 (AV) and phase was calculated from the difference between DA
calcium phosphate (CP). The EVG is highly hydroscopic and DO (relative density of the granules at nil pressure).
and deliquescent and is stored over silica gel in a Kawakita Analysis: The Kawakita equation 8 describes
dessicator. Efforts to use common diluents such as the relationship between the volume reduction of
lactose, starch, and magnesium carbonate for tablet powder column and the applied pressure;
formulation of the extract produced tablets with
defects such as sticking and picking. In the attempt C = [Vo V/ Vo] = [abP/1 + bP](4)
to check the deliquescent characteristics of the extract,
efflorescent diluents were selected for this formulation Where, C, is degree of volume reduction, Vo is Initial
process. volume, V is volume of powder column under the
applied pressure P. a, b are constants characteristic to
The Heckel equation has by far been the most popular powder being compressed. The equation above can be
in recent years among pharmaceutical scientists, and re arranged in linear form as:
many apparent yield pressure values (in-die, Py) and
mean yield pressure values (out-of-die) of active P/C = P/a + 1/ab .. (5)
substances and tableting excipients have been From the graphical presentation of P/C versus P, the
published 4. The model has often been applied to study
constants maybe evaluated. The constant a, is given
powder mixtures and to evaluate granule
as a reciprocal of the slope from the linear portion of
manufacture. Of recent, scientists have also made
the plot and equivalent to the value of C at infinitely
attempts to use the Heckel relation for predicting
high pressures. 1/ab is the intercept. a, gives an
powder characteristics of active crude plant extracts 2.
indication of the maximum volume reduction available
Despite the versatility of the Heckel equation however, and is considered to describe the compressibility of a
drawbacks and limitations to its use have been powder, while b is considered to describe an
reported 4. Some scientists have used more than one inclination toward volume reduction. However, the
equation to try to eliminate the shortcomings of the actual physical meaning of the constants a and b have
other 5, 6. Hence, in this study, both Heckel and been in question 9. Consequently, Kawakita in 1983
Kawakita plots have been used to assess the have applied another equation in describing the
compression characteristics of EVG in combination volume reduction on tapping and vibrating processes,
with the three efflorescent diluents; AR, CP and AV. where the pressure P, is replaced by the tapping
number, N 10.
Heckel Analysis: The plots constructed according to
the Heckel equation 7 were used to characterize the N/C = [(1/a) N 1/ab] (6)
consolidation behavior of the formulations: Where, N is the tapping number, C is the degree of
Ln [1/(1D)] = KP +A (1) volume reduction and a and b are constants. C in
equation vi is given by;
Where D is the ratio of the density of the powder mass
at pressure P to the density of the powder mixture C = [Vo VN] Vo .. (7)
(i.e., relative density); K, the slope of the straight
Where Vo is the initial apparent volume and VN, the passed through a 1000 m screen to break up
volume at tapping number N. The constants of agglomerates.
Kawakita equation can be used to estimate the flow
and cohesiveness properties of powders. Constant a, 3. Granule Analysis:
describes the compressibility and constant 1/b a. Moisture content analysis: One gram (1.0g) of
describes cohesive properties of powders or the the sample was transferred into each of several
fastness of how the final packing stage is achieved 9. Petri dishes and then dried in an oven at 105C
MATERIALS AND METHODS: until a constant weight was obtained. The
moisture content was then determined as the
Materials: These include Gelatin (May and Baker, ratio of weight of moisture loss to weight of
Germany), aerosil 200 (GmbH, Meggle, Germany), sample expressed as a percentage.
avicel PH-103 (FMC Corporation, USA) calcium
phosphate (BDH chemicals Ltd., Poole, England), maize b. Angle of repose: The static angle of repose, a,
starch (May and Baker, Germany) and the leaves of was measured according to the fixed funnel
Vernonia galamensis (collected from the natural and free standing cone method. A funnel was
habitat of Ahmadu Bello University, Zaria, Nigeria and clamped with its tip 2cm above a graph paper
identified in the herbarium unit of the Department of placed on a flat horizontal surface. The
Biological Sciences of the University where a sample powders were carefully poured through the
was deposited with a voucher specimen number 994). funnel until the apex of the cone thus formed
just reached the tip of the funnel. The mean
Methods: diameters of the base of the powder cones
were determined and the tangent of the angle
1. Preparation of the extract: Leaves of Vernonia of repose calculated using the equation:
galamensis were plugged from the main stem in
June, 2010 and washed, air dried, milled to a Tan a = 2h/D . (1)
coarse powder (particle size 1000 um) and
macerated in distilled water for 24 h at room c. Bulk density, Tapped density, Hausners ratio
temperature and the liquid extract filtered through and Carrs index of compressibility: Thirty
a calico cloth and concentrated to a ratio of 5:1 gram (30 g) quantity each of the granules was
using a rotary evaporator. The concentrated filtrate carefully poured through a short stem glass
was then transferred into a tray and dried in an funnel in a 100ml measuring cylinder and the
oven at 40 C, pulverized using a mortar and pestle volume, V0, occupied by the granules without
and then passed through a 150 m sieve. tapping was noted. After 100 taps on the table,
the occupied volume V 100 was read. The bulk
2. Preparation of granules: The wet granulation, a and tap densities were calculated as the ratio of
versatile process, was employed because of the weight to volume (V 0 and V 100 respectively).
very high humidity and poor flow property of the Carrs index and Hausners ratio were
extract 11. Appropriate quantities of the dry extract calculated using the following equations:-
and diluent ratio 1:1.4 were mixed in a mortar for 5
minutes. Disintegrant (maize starch, 6.8% w/w) Carrs index= Tapped density Bulk density x 100 (2)
was added and mixing continued for another 5 Tapped density
minutes. The liquid binder prepared using gelatin
Hausners ratio = Tapped density (3)
5% w/v in water was added in 1-mL portions and
Bulk density
mixed with a pestle. The moistened mass was
forced through a 1000m sieve, dried at 40 C for 2 4. Preparation of compacts: The tablet formula was
h to give a moisture content of 4% 6%, designed by varying the type and quantities of the
determined on an Ultra X moisture balance (August excipients to obtain tablets of highest quality
Gronert Co., Germany). The granules were again (Table 1). Tablets equivalent to 300mg of granules
were produced by compressing the granules for 60 fitted with 10.5 mm flat punch and die set. After
s at 26.25 KN (303 MNm-2) using a single punch ejection, the tablets were stored over silica gel in a
tablet machine (Tianxiang and Chentai dessicator for 24 h to allow for elastic recovery and
Pharmaceutical Machinery Co Ltd, Shanghai, China) hardening.
TABLE 1: MEAN GRANULE SIZE AND HECKEL CONSTANTS FOR DIFFERENT FORMULATIONS
2
Diluent Binder (GLT) (%) Py (MNm-2) A DA Do DB R
AR 5.0 711.241.70 -0.180.01 -0.19 0.180.07 -0.37 0.995
AV 5.0 323.212.40 -0.690.01 -0.99 0.150.04 -1.14 0.999
CP 5.0 115.942.10 -2.190.02 -7.95 0.300.01 -8.25 0.999
GLT = Gelatin, AR = Aerosil 200, AV = Avicel PH 101 and CP = calcium phosphate. Results were expressed as mean SD of three runs
Data analysis: The graphs were plotted and data extremely hygroscopic and deliquescent chondroitin
analyzed using GraphPad Prism version 5.03 software. sulfate were by plastic flow 14. The increase in slope at
The data used to plot the graphs were the mean of higher pressure indicates an increase in the rate of
three readings SD, granule size, moisture content densification as the void spaces between particles
decrease. Figure 1 also shows that the EVG/AV
RESULTS AND DISCUSSIONS: Three types of powder compacts were compressed at higher relative densities
compression behavior have been identified based on than those of EVG/AR and EVG/CP.
the Heckels equation, namely type A, B and C 12.
Figure 1 depicts the Heckel plots obtained for the The tendency of the material to deform either by
granulations formulated with AR, AV and CP as diluents plastic flow or fragmentation is described by the yield
and GLT at 5% w/v concentration as binder. The plots pressure Py, which is an important indication of granule
especially for formulations containing AR and AV compressibility. A faster degree of plastic deformation
exhibited linear and near parallel relationships at all is reflected by a low Py value (steep slope) in a general
applied pressures, where increase compression sense. Table 1 show that formulations made with AV as
pressure significantly increase the relative density of diluent gave lower Py values than those with either AR
the compacts. This implies that the plots are indicative or CP, indicating that granules of the former deformed
of type-A materials and that all the granules principally plastically at lower pressures than those of the later
undergo deformation by plastic flow 13. ones. But negative intercepts were observed in all the
different formulations using the selected efflorescent
diluents. This negative values of intercepts may be due
to the intrinsic characteristics of the extract; being
deliquescent in nature. The negative intercepts gave
rise to negative values of both DA and DB by
calculation.
phase or the extent of granule fragmentation by the Previous study have indicated that the smaller the
use of the Heckel equation. This is a limitation of the values of a, the better the fluidity 9. The value of PK
equation in this study. for formulations with AR is highest implying that the
cohesiveness of the granules would be higher than
Figure 2 shows the kawakita plots for Vernonia others. The low value of PK in other formulations is
galamensis tablet formulations containing selected indicative of the reduction in cohesion. A low value of
diluents and GLT as binder, where a linear relationship PK is indicative of materials that are soft and that
between N/C and N is obtained at all compression readily deform plastically under pressure 9.
pressures used with correlation coefficient 0.99 for
all the formulations, and hence, the equation can be CONCLUSION: Two models namely; Heckel and
used to predict the densification mechanisms of the Kawakita models were fitted to the pressure-density-
Vernonia galamensis formulations better than the volume data. Although the Heckel model presented
Heckel equation where negative intercepts were acceptably high R2 values, the negative values of DA
observed. and DB made it difficult to practically explain the
degree of densification at zero and low pressures and
the particle rearrangement phase and extent of
granule fragmentation. We can therefore conclude
that the Kawakita model with high R2 values and no
negative intercept is preferred in explaining the
compressional characteristics of granules of Vernonia
galamensis prepared using GLT as binder along with
the selected diluents (AR, AV, CP).
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tablets. IV. The effect of particle size on the mechanical Chemistry, Bradford, 1970: 33.
strength of tablets. Acta Poloniac Pharmaceutica Suecica 1982; 13. York P and Pilpel N: The tensile strength and compression
19: 381390. behavior of lactose, four fatty acids and their mixtures in
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mechanical properties of paracetamol tablet formulations. 1973; 25: 111.
African Journal of Pharmacy and Pharmacology 2008; 2: 2001- 14. Ebube NK, Mark W and Hahm H: Preformulation studies and
2006. characterization of proposed chondroprotective agents:
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Pharmacy. Henry Kimpton Publishers, London, Edition 2, 1976: Development and Technology 2002; 7: 457-469.
321-358.
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