Documente Academic
Documente Profesional
Documente Cultură
DOI 10.1007/s12272-009-1231-0
(Received October 25, 2008/Revised January 14, 2009/Accepted January 19, 2009)
A study has been made of the effects of sun and oven drying methods on the physicochemical charac-
teristics and compressibility of Okra powder and the release properties of its metronidazole tablet for-
mulation. Corn starch was used as the reference standard. The mechanical properties of the tablets were
evaluated using crushing strength and friability, while the release properties were determined using the
disintegration times and dissolution rates. The results obtained showed that sun-dried Okra powder had
smaller particle size, exhibited good flow and possessed higher hydration and swelling capacities com-
pared to the oven dried samples. The compressibility of Okra powders assessed by the indices of plas-
ticity from Heckel (Py) and Kawakita plots (Pk) showed that sun dried Okra powders had higher Py but
lower Pk values than the oven-dried Okra powder. Metronidazole tablets formulated with oven dried
Okra powder formed stronger tablets than tablets containing sun dried Okra powder. Generally, tablets
containing sun dried Okra powders had faster disintegration and dissolution than tablets formulated with
oven-dried powder. The results suggest that the choice of drying method during the processing of phar-
maceutical raw materials is critical to its physicochemical properties and the release properties of its tab-
let formulations.
Key words: Drying methods, Okra, Physicochemical and release properties, Metronidazole tablets
259
260 L. G. Bakre and K. T. Jaiyeoba
when absorbed is converted to heat, chemical and vibra- 15 mL plastic centrifuge tubes, distilled water was added,
tional energy. It is the heat energy that results in evapora- the tubes covered with parafilm and the contents mixed
tion of moisture from the material. However, the drying on a vortex mixer for 2 minutes. The mixture in each tube
conditions and choice of drying method may significantly was left for an additional 3 minutes and then centrifuged
affect structural and functional properties such as tablet- at 3000 g on a centrifuge (CFB-502-010, Griffin and
ing behaviour of pharmaceutical materials (Bataile et al., George, U.K). The supernatant was decanted and the
1993; Chatract and Staniforth, 1990), (Habib et al., 2002) sediment weighed. The weight of water absorbed and re-
and subsequent formulation characteristic (York, 1983, tained was determined as the gain in weight of dry sample
1992). from Eq. (1). Determinations were made in quadruplicate.
The aim of this study is to compare the effects of sun
Hydration Capacity
and oven drying methods on the physicochemical and
compression characteristics of Okra powder and the ( weight of tube + se dim ent) – weight of tube
= ---------------------------------------------------------------------------------------------------------- (1)
release properties of its metronidazole tablet formulation. Sample weight (dry basic)
Sun dried (FOP-SD) powder was prepared by drying Okra
pods in the sun for 72 h at 67% relative humidity while Moisture sorption capacity
the oven dried powder (FOP-OV) was obtained by drying Two gram of the Okra powder was accurately weighed
the pods in the oven at 60oC for 9 h. and evenly distributed over the surface of a 70 mm tarred
petri dish. The sample was then placed in a large desicca-
MATERIALS AND METHODS tor containing distilled water in its reservoir (RH = 100%).
The desiccator was stored at room temperature at various
The materials used were metronidazole BP and corn time intervals over a five-day period. The weight gained
starch BP (BDH Chemical, Poole, U. K.) polyvinylpyroli- by the exposed sample was recorded and the amount of
done, PVP (30,000, Merck, Germany), lactose (DMV water sorbed was calculated from the weight difference.
Veghel, Netherlands), magnesium stearate (Hopkin and
Williams, England), Okra powder prepared in Pharma- Swelling capacity
ceutics laboratory, University of Ibadan, Nigeria. Water Three gram of the Okra powder was placed in a 50 mL
was double distilled and every other chemical was of ground-glass stoppered graduated cylinder. 20 mL of water
analytical grades. was added and the cylinder closed. This was shaken
vigorously every 10 minutes for 1 h and then allowed to
Preparation of Okra powders stand for 5 h. At 2.5 h after the beginning of the test, any
A 5.0 kg weight of fresh Okra pods from which the large volume of liquid retained in the layer of the sample
stalk and the apex of the pod had been removed was and particles of the drug floating at the surface of the
weighed, sliced with a hand knife and spread in the sun liquid was released by rotating the cylinder about a
for 72 h. The sun drying was done between 9:00 hrs and vertical axis. The volume occupied by the sample includ-
16:00 hrs daily. The average temperature during this ing any adhering mucilage was noted. The test was
period was 33oC and the relative humidity was 67%. The performed in triplicate and the swelling index calculated
sun dried pods were then crushed into tiny bits in a from the mean of the three tests.
mortar and then pulverized in an osterizer blender to VS
produce powdered Okra labeled as FOP-SD. Fresh okra Swelling Capacity = ------ (2)
VO
pods without the apex and the stalk was prepared as
above but dried in an oven (Gallenkamp, UK), at 60oC
for 9 h to produce powdered Okra labeled as FOP-OV. Bulk and tap densities
The bulk density was determined by a modification of
Evaluation of physicochemical properties of Okra the method of Kumar and Kothari, 1999. 25 g of each of
powders the Okra powder was passed through a 1.00 mm mesh
Elemental Constituents of the Okra powder screen to break up agglomerates which had been formed
A 500 mg quantity of each Okra powder was introduc- during storage. This was then levelled carefully (without
ed into the Link Analytical XR300 (Wallis Worthing, compacting) into a 100 mL cylinder. The bulk density
Europe). The results of the elemental constituents was was calculated from the ratio of the weight of the sample
displayed on the screen. to the bulk volume. This was carried out in triplicate and
the final bulk density was the mean determination of the
Hydration capacity three values. Tap density was determined by subjecting
Four hundred (400) mg samples were placed in each of the powder to 300 taps by a standardized tapping proce-
Effects of Drying Methods on Okra Powder Properties 261
dure of 38 taps per minutes (British Standard 1460) and From the value of the intercept, A, the relative density,
then repeated with 700 taps. The final tapped volume was Da, can be calculated using the following equation
obtained when the difference between 200 times taps is (Humbert-Droz et al., 1983):
less than 2%. The powder porosity was computed from –A
Da = 1 – e (6)
the bulk density and true density using the equation below:
The relative density of the powder bed at the point
bulk density
e = 1 – ---------------------------- (3) when the applied pressure equals zero, Do, is used to
true density
describe the initial re arrangement phase of densification
as a result of die filling. The relative density, Db,
Particle or true density describes the phase of rearrangement at low pressures and
The particle densities of the Okra powder samples and is the difference between Da and Do.
corn starch were determined by the pycnometer method The Kawakita and Ludde (1970/71) equation is used to
using liquid immersion technique with benzene as the study powder compression using the degree of volume
displacement liquid. A 50 mL pycnometer bottle was reduction, C, and is written as:
weighed when empty (w). This was filled with benzene
P P 1
to the brim till it overflows. The excess was wiped off ---- = --- + ------ (7)
C a ab
the bottle and its contents were weighed (W1). The
difference between the two weights recorded was calcu- The constant a is equal to the minimum porosity of the
lated (W2). A 2 g quality of the Okra pod powder was material before compression; the constant b, which is
weighed (W3) and quantitatively transferred into the termed the coefficient of compression, is related to the
pycnometer bottle. The excess solvent was wiped off and plasticity of the material. The reciprocal of b is related to
the bottle weighed again (W4). The particle density r was the pressure term Pk, which is the pressure required to
calculated from the following equation. reduce the powder bed by 50% (Shivinand,and Sprockel,
W 2 ⋅ W3 1992; Lin and Chan, 1995)
ρ = ----------------------------------------- (4)
50(W1 + W3 + W4)
Preparation of tablets
The results given are the means of three determina- Batches (500 mg) of metronidazole formulations con-
tions. taining 50% w/w metronidazole powder, 2.5%-15%
disintegrant, 5% PVP (binder) and lactose diluent were
Determination of precompression density of Okra compressed for 30s into tablets on a hydraulic hand press
powders (Model C, Carver Inc., Menomomee Falls, WJ, USA)
The precompression density (Do) was calculated as a using a 12.5 mm die and flat faced punches lubricated
ratio of the loose bulk density to the particle density. with a 2%w/v dispersion of magnesium stearate in 96%
ethanol. The tablets were stored over silica gel for 24 hr
Preparation of Okra powder compacts to allow for elastic recovery and hardening, and prevent
Five hundred (500) mg of the Okra powder were com- false low yield values. Tablet weights and dimensions
pressed for 30 seconds into tablet with pre-determined were determined within ±1 mg and 0.01 mm respectively.
loads using a hydraulic hand press. The tablets weight
and dimensions were determined within ±1 mg and 0.01 Determination of tablet properties
mm respectively. Their relative densities (D) were calcu- Crushing strength
lated. Heckel plots of In (1/1-D) versus the compression The load (N) required to diametrically break the tablet
pressure, P and Kawakita plots of P/C vs. P were con- (crushing strength) was determined at room temperature
structed. using a Monsanto Hardness tester. Ten tablets, randomly
selected from each batch were used in the test. Each
Compaction data analysis tablet was held between a fixed anvil and a moving jaw
The Heckel (1961a) equation is widely used for relating apparatus until the tablet just fractured. The value of the
the relative density, D, of a powder bed during compres- load on the gauge at this point gives a measure of the
sion to the applied pressure, P. It is written as: tablet crushing strength in Kilogram force (KgF). Deter-
minations were made in quintuplicate for each batch of
1
In⎛ -----------⎞ = KP + A (5) the tablet tested.
⎝ 1 – D⎠
The slope of the straight line portion, K, is the reci- Tablet friability
procal of the mean yield pressure, Py, of the material. The percentage friability of the tablet was determined
262 L. G. Bakre and K. T. Jaiyeoba
using the Veego tablet friability apparatus (Veego Scien- materials. Oven dried Okra powder had a relatively high
tific Devices, Mumbai, India). The weights of 10 tablets bulk density value which is of advantage in tableting
were taken and then placed in the friabilator which was because of a reduction in the fill volume of the die. Oven
then operated for 4 minutes at 25 revolutions per minute. dried sample had higher tapped density value and are
The tablets were collected, dusted and weighed again. more porous than the sun dried sample. These differences
The percentage weight loss was calculated as percentage might be due to different particle shape and differing
friability. Determinations were made in duplicate. percentage of fines both of which significantly affect the
packing arrangement of particles. Table I shows that both
Disintegration test the sun and oven dried Okra powder had greater hydration
The disintegration times of the tablets were determined and swelling capacities than corn starch. This implies that
in distilled water at 37±0.5oC using BP Manesty disin- the rate of water uptake and the extent of water retention
tegration test unit (Manesty Machines, Poole, U.K). Six by the Okra powders are higher than those of corn starch.
tablets from each formulation were placed on the wire Thus, tablets formulated with Okra powders as disintegrants
mesh just above the surface of the distilled water in the may be expected to exhibit faster disintegration than
tube and the apparatus was started simultaneously. The those with corn starch. However, the sun dried sample
time taken for all the tablets to disintegrate and go through had higher hydration and swelling capacities than the
the wire mesh was recorded. Determinations were made oven dried sample. The high hydration capacity suggests
in triplicate. an ability to hold large amounts of water in the pores
between the powders. Water uptake is known to precede
Dissolution test disintegration process (Caramella et al., 1986; Wan and
The dissolution test of metronidazole from the tablets Choong, 1986) and several workers have documented the
was studied in a rotating basket BP Apparatus II [Veego relationship between the disintegration process and the
digital dissolution tester, India] operated at 100 rpm using development of a disintegrating force inside a compact
900 mL of 0.1 mL hydrochloric acid maintained at 37± (Colombo et al., 1998). Consequently, determination of
0.5oC. Five (5 mL) samples were withdrawn at specified swelling capacity as well as the hydration capacity of a
time intervals and immediately replaced with 5 mL powder will be indicative of its potentials as a tablet
samples of fresh buffer solution maintained at the same disintegrants (Iwuagwu and Okoli, 1992). Also it may be
temperature. The amount of metronidazole in each sample expected that the mechanism of action of the Okra
was analysed spectrophotometrically at 250 nm on a SP6- powders would likely be via uptake of large amount of
450 UV/VIS spectrophotometer (Pye Unicam, Middlesex, water which will break interparticulate as well as hydrogen
England). Determinations were made in triplicate. bonds in the compacts. However, it has been observed
that hydration capacity may not be an absolute index of
RESULTS AND DISCUSSION disintegrant efficacy (Adebayo and Itiola, 1998a)
Effect of drying methods on physicochemical proper- Effect of drying methods on compressional character-
ties Okra powder istics of Okra powder
The British Pharmacopoeia (BP, 2005) gives limit tests The Heckel plots of In (1/1-D) versus the applied
for a number of possible contaminants in pharmaceutical pressure are shown in Fig. 1. The curves for the sun dried
raw materials but the requirements are not specific on the sample and corn starch shows two distinct region; a short
exact tolerable level of any possible contaminants. However, region of rapid increase in density with increase in
it should not be presumed that unusual impurities are compression pressure (32.1 to 83.5) followed by a region
tolerated. Heavy metals like lead which are highly un- of apparent linearity. This is typical of Type A materials
desirable in pharmaceutical raw materials were absent in which consolidate mainly by plastic deformation. The
both the sun and oven dried samples. Silicon is present in Heckel plots for the oven dried sample flatten out into a
both samples and might have been introduced by earthly plateau at all compression pressures. This resembles a
too high or too low. Metronidazole tablets formulated with Table IV. Disintegration and Dissolution characteristics of
corn starch formed harder tablets than those formulated Metronidazole tablets containing powders at concentrations
with the Okra powders (Table III). In addition, there was that produced the best dissolution profiles
a decrease in tablet strength as the concentration of Okra Powder Conc %w/w DT(min) T50 (min) T90 (min)
powder increased in tablets containing Okra powder. This FOP-SD 17.5 18.17 5.00 19.80
could be attributed to a decrease in metronidazole particle FOP-OV 12.5 14.48 6.00 17.00
–to- particle contacts as a result of increased Okra powder Corn starch 12.5 15.65 3.40 13.00
concentration which consequently resulted in weak bond
formation. Tablets containing the oven dried Okra powder
formed harder tablets than tablets formulated with the sun tablets containing powders at concentrations that produc-
dried Okra powder. The friability test is especially impor- ed the best dissolution profiles. Tablets formulated with
tant because the tablet is likely to be subjected to various sun dried powder disintegrated faster and had lower T50
abrasive motions during production and subsequent use. values than those containing the oven dried Okra. There
There are now requirements for it in the British Pharma- was a fair linear correlation between T50 and disintegra-
copoeia (BP, 2005) but with no clear limits for acceptance tion time, DT, for FOP-OV (r = 0.875, P<0.05) and FOP-
or rejection of tablet batches probably because the SD (r = 0.858, p< 0.05). All the tablets formulated with
principles of the test are not understood (Podczeck F and either the sun or oven dried Okra powders passed the
Sharma, 1996). Generally, metronidazole tablets formulated British Pharmacopoeia (BP 2005) specifications for disin-
with the sun and oven dried Okra powders had friability tegration time of uncoated tablets (<15 minutes) while the
values less than 1% except tablets formulated with 15 time required for 90% drug release (T90) was also within
%w/w FOP-SD and 7.5 %w/w FOP-OV. By convention, one hour which is characteristic of immediate release
tablets that lose not more than 1% of their weight in the formulations. In addition, both the tablets formulated with
friability test are usually considered acceptable. In addi- sun and oven dried powders passed the BP dissolution
tion, tablet formulations containing the oven dried Okra test for tablets which specifies that at least 70% of the
powder are less friable than those formulated with the drug substance should be in solution after 30 minutes.
sun dried Okra powder. The values of crushing strength
(CS) and friability (F) provide the measures of tablet Mechanism of the effects of the drying methods
strength and weakness, respectively. Thus, the crushing The differences in the physicochemical properties of
strength-friability ratio can be useful as an index of tablet the sun and oven dried Okra powders and the release
quality. However, the crushing strength-friabrasion/disin- properties of their tablets might be as a result of greater
tegration time ratio (CS-F/DT) has been suggested as a amount of heat absorbed during oven drying than in sun
better index of tablet quality because in addition to mea- drying. In oven drying, the materials absorb heat by all
suring tablet strength and weakness, it simultaneously the three mechanisms of heat transfer namely conduction
evaluates any negative effects of these parameters on through the drying tray, convection of the hot air in the
disintegration time (Upadrashta et al., 1992). oven and radiation from the walls of the oven. This
Metronidazole tablets formulated with oven dried Okra generates large amount of heat energy which may cause
powder had higher CS-F/DT values than tablets contain- rotation of the entire molecules of the okra powder,
ing sun dried Okra powders at all the concentrations used vibration of chemical bonds and changes in electron
in this study. However, tablets formulated with corn configuration of the okra powder molecules which may
starch had higher CS-F/DT values than tablets containing consequently lead to significant structural changes in the
the Okra powders. okra powder molecules. The structural changes in turn
affect the physicochemical properties of the material.
Effect of drying method on the release properties of Similar observations were made by Ayanwale et al. (2007)
metronidazole tablets when they studied the effect of sun-drying and oven
Tablets containing the Okra powders generally passed drying on the nutritive value of meat pieces in hot humid
the official disintegration test for uncoated tablets i.e. <15 environment. On the other hand, the solar radiation is
minutes (BP, 2005). Generally, sun dried Okra powder transmitted only by radiation, it is unevenly distributed
had shorter disintegration times than oven dried powder and it varies in intensity from one geographical location
except at concentrations of 2.5 and 15 %w/w. Tablets to the other depending on the latitude, season and time of
containing the Okra powders showed good dissolution the day. Cloud formation may also hinder the overall
profile. There was a general increase in dissolution rates atmospheric transmission of solar radiation to a degree
as concentrations increases. Table IV shows the disinte- determined by the thickness and density of clouds. Very
gration and dissolution characteristics of metronidazole dense clouds, about 1000 m in thickness, are said to
266 L. G. Bakre and K. T. Jaiyeoba
reflect back into space more than 90% of the incident solar Chatrath, M. and Staniforth, J. M., The relative influence of
radiation (Acra, 1994). All these reduce the intensity and dielectric and other drying techniques on the physico-
the effect of the total solar radiation that strikes the mechanical properties of a pharmaceutical tablet excipient.
particles of the materials exposed to it. Part I: Compaction characteristics. Drying Technol., 8, 1089-
1109 (1990)
CONCLUSIONS Colombo, P., Colombo, P., Conte, U., Ferrari, F., La Manna,
A., Gazannagi, A., and Peppas, N. A., A physical analysis
The study showed that the sun and oven dried powders of the phenomenon of tablet disintegration. Int. J. pharm.,
had different physicochemical and compressional charac- 44,177-186 (1988).
teristics that are attributable to the relative amount of heat Deodhar, U. P., Paradkar, A. R., and Purohit, A. P., Preliminary
absorbed during the drying process. Therefore, the choice evaluation of Leucaena leucocephala seed gum as a tablet
of the drying method during the processing of local phar- binder. Drug Dev. Ind. Pharm., 24, 577-582 (1998)
maceutical raw materials is critical to the physiochemical Habib, Y. S., Augsburger, L. L., and Shangraw, R. F., Produc-
properties of the material and the release properties of tion of inert cushioning beads: effect of excipients on the
their tablets. physico-mechanical properties of freeze-dried beads con-
taining microcrystalline cellulose produced by extrusion
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