INTRODUCTION:

Gums are widely employed in the pharmacy as thickeners, suspending agents, emulsifying agents, binders and film formers. With the increase in demand for natural gums, it has been necessary to explore the newer sources of gums to meet the industrial demands¹. There are reports about the successful use of Ocimum gratissimum, Butea monospermama and Leucaena leucocephala seed gum as suspending agent^{2, 3, 4}.

A pharmaceutical suspension is a coarse dispersion in which insoluble solid particles are dispersed in a liquid medium. The particles have diameter for most part greater than 0.1 micrometer⁵. A suspension is a heterogeneous or biphasic system consisting of solid phase in liquid phase⁶, it necessary to include in the dosage form, a stabilizer or suspending agent which reduces the rate of settling and permits easy redispersion of any settled particulate matter both by protective colloidal action and by increasing the consistency of the suspending medium⁷ .

Suspending agents are (i) inorganic materials, (ii) synthetic compounds and (iii) polysaccharides. Natural gums like acacia, tragacanth, khaya, karaya and albizia belong to the latter group⁸. Recent advances in natural suspending agents have been very impressive.

These materials have attracted due to their novel properties as they are derived from plant sources. Hence, they are termed to be biocompatible, biodegradable and cheap⁹.

Leucaena latisiliqua [family: Leguminosae (Mimosaceae)] is a gum–producing tree wildly found in India southern region¹⁰ (National Academy of Sciences). The seed mainly contains predominantly carbohydrates. Hence, in the present investigation an attempt has been made to evaluate the suspending property of Leucaena latisiliqua as a suspending agent in the formulation of acetaminophen suspension and compared with the commonly available natural suspending agents such as acacia, tragacanth and gelatin. Acetaminophen was chosen for this investigation because it is a typical representative of practically insoluble drugs which would require a suspending agent to be prepared as a liquid dosage form¹¹.

MATERIALS AND METHODS:

The materials used for the preparation of suspension includes, suspending agent isolated from Leucaena latisiliqua (Seed). acetaminophen, tragacanth, gelatin, gum acacia, benzoic acid, glycerin, amaranth solution, raspberry syrup and chloroform water (vehicle).

Plant Material:

The seeds of Leucaena latisiliqua were collected in Erode (Tamilnadu)and its surrounding areas. The authentication of plant material was done by “Botanical Survey of India” (TNAU) Coimbatore, Tamilnadu. Seed specimen sample is kept in the laboratory for future use. The seeds of Leucaena latisiliqua were washed thoroughly with water to remove the adhering materials, before isolation of the natural mucoadhesive agent from it.

Isolation of natural suspending agent from the seeds:

The seeds of Leucaena latisiliqua were cleaned by soaking them (100g) in 200 ml of warm water. Seeds were swell and to detach suspending material from the kernel and the tegmen. The resultant solution was treated with absolute alcohol to precipitate the polysaccharide. The mass was then dried, pulverized and stored in a desiccate for further use.

Figure- 1 Sedimentation profile of suspensions made with different concentrations (0.5, 1.0, and 1.5 and 2 % W/V) of gum of Leucaena latisliqua,acacia,trgacanth and gelatin.

Preparation of acetaminophen suspension:

Compound tragacanth powder (0.5 g) and 10 g of acetaminophen were triturated together with 20 ml of raspberry syrup to form a smooth paste. Benzoic acid solution (2 ml) and 1ml of amaranth solution were added gradually with constant stirring and then mixed with 50 ml of chloroform water double strength. The mixture was transferred into a 100 ml amber colour bottle, made up to volume with distilled water and then shaken. The same procedure was adopted using 1.0, 1.5, and 2.0 g of compound tragacanth powder. The above procedure was repeated with gum acacia, gelatin and Leucaena latisiliqua.

Evaluation of Toxicity:

The male albino rats of Wistar strain weighing 160-200 gm were divided into different groups comprising of six animals each. The control group received normal saline 25ml/kg. The other groups received 100, 200,400,600,800,1000,2000,3000 and 4000 mg/kg of gum suspension in normal saline orally. The animals were observed continuously for the behavioral changes for the first 4 hours and then observed for mortality if any for 24 hours¹².

Physical characteristics of Leucaena latisiliqua:

Swelling Index:

Natural suspending agent (Leucaena latisiliqua) 1 g was taken in a China dish then 10 ml of distilled water was added and the mixture was shaken and allowed to stand for 1 hour. After 1 hour the remaining water in china dish was discarded and the weight increase of the natural suspending agent was rated employing the formula.

Swelling index %= (w₂ – w₁/w₁) x 100 --------------- (1)

Where,

w₁ - weight of natural suspending agent before swelling

w₂ - weight of natural suspending agent after swelling

Figure-2 Rheological behavior of suspensions made with 3%w/v concentrations gum of Leucaena latisliqua, tragacanth, acacia and gelatin.

Measurement of viscosity:

The rheological behavior of the suspensions 3%w/v prepared with Leucaena latisiliqua acacia, tragacanth and gelatin were studied using Brookfield synchroelectric viscometer, spindle number 1 of low viscosity type with gear speed ranging 0.3 to 0.6 rpm. The dial readings for both up-curve and down curve were recorded and the experiment was repeated for three times. Using these observations, the rate of shear was calculated. The results were recorded and the rheogram were obtained by plotting rate of shear, G/sec versus shearing stress F, Dyne/cm² (Figure. 2).

Flow rate:

The time required for each suspension sample to flow through a 10 ml pipette was determined and the apparent viscosity (ηα in mls-1) was calculated using the equation:

Flow rate = ηα = Volume of pipette (ml) ------- (2)

Flow time (s)

Sedimentation volume:

Each suspension (100 ml) was stored in a 100 ml measuring cylinder for 6 days at 35^oC. Observations were made every 24 h for 6 days. The sedimentation volume, F (%), was then calculated using the following equation.

F = 100 V_u/V_o --------------------------------- (3)

Where, V_uis the ultimate volume of sediment and V_o is the original volume of the suspension.

Table-1 Determination of Sedimentation volume

Suspending agent

Concentration

Sedimentation volume in Days

Average

Leucaena latisliqua

0.5 %

1 %

1.5 %

2 %

0.91

0.97

0.86

0.96

0.81

0.94

0.99

0.72

0.94

0.97

0.94

0.70

0.92

0.95

0.94

0.68

0.90

0.95

0.93

0.78

0.93

0.97

0.96

Acacia

0.5 %

1 %

1.5 %

2 %

0.30

0.34

0.39

0.45

0.27

0.32

0.35

0.41

0.24

0.32

0.34

0.39

0.24

0.30

0.32

0.39

0.20

0.28

0.30

0.36

0.19

0.28

0.33

0.24

0.30

0.33

0.38

Tracaganth

0.5 %

1 %

1.5 %

2 %

0.59

0.66

0.61

0.6

0.58

0.66

0.60

0.6

0.58

0.65

0.60

0.59

0.57

0.65

0.60

0.58

0.56

0.64

0.59

0.58

0.55

0.62

0.59

0.58

0.57

0.64

0.59

0.58

Gelatin

0.5 %

1 %

1.5 %

2 %

0.69

0.70

0.76

0.85

0.68

0.70

0.76

0.85

0.68

0.96

0.76

0.85

0.68

0.69

0.75

0.84

0.67

0.69

0.75

0.84

0.67

0.69

0.74

0.83

0.67

0.74

0.75

0.84

Table 2: Physical Properties of suspension

Suspending agent

Concentration % w/v

Flow rate mls^-1

Swelling index (in water)

Leucaena latisliqua

0.2

0.4

0.6

0.8

0.039

0.035

0.033

0.030

13.29 ± 2

Tracaganth

0.2

0.4

0.6

0.8

0.035

0.031

0.028

0.026

8.92 ± 2

Acacia

0.2

0.4

0.6

0.8

0.029

0.024

0.018

0.014

11.24 ± 3

Gelatin

0.2

0.4

0.6

0.8

0.037

0.033

0.030

0.029

13.18±2

Particle size analysis:

After shaking, 10 ml of each sample was separately transferred into 200 ml cylinder. Distilled water (150 ml) was then added, mixed and 10 ml aliquot was removed at a distance of 10 cm below the surface of the mixture and at 15, 30 and 60 minutes. This was transferred into an evaporating dish and evaporated to dryness in an oven at 105^oC and the residue weighed. The particle diameter (d in cm) was then calculated using the Stokes equation⁶.

D = 18ηh -------------------------- (4)

(ρ_s-ρ_o) gt

Where, h is the distance of fall of the particle (cm), t is the time (s), η is the viscosity of the dispersion medium (centipoise), ρ_s – ρ_o is the density gradient between the dispersed particles and the liquid (g cm^-3) and g is the gravitation constant (cm s^-2).

RESULTS AND DISCUSSION:

Toxicity study of the gum revealed in that no behavioral changes for first four hours and no mortality was observed even at the dose level 4000mg/kg body weight after 24 hours, indicating the safety of the gum.

The sedimentation volume profile of the suspensions prepared with gum of Leucaena latisiliqua, tragacanth, gelatin, gum acacia, are shown in Table-1 and figure-1, the sedimentation volume of the suspensions prepared with gum of Leucaena latisiliqua, are comparable with the suspensions prepared using gelatin but low then tragacanth and gum acacia.

The effects of the type and concentration of the suspending agents on flow rate and swelling index are as shown in Table- 2.

The rheological behavior of the suspensions prepared with gum of Leucaena latisiliqua, tragacanth, gelatin and gum acacia are given in figure. 2. The results reveal that the suspensions are pseudoplastic in their behavior and their viscosity decreases with increase in shear rate, which is an essential property in the formulation of suspension.¹³

These observations indicate that the suspending property of Leucaena latisiliqua gum is comparable with that of gelatin but better then tragacanth and gum acacia.

Since, all the suspension produces sediment on storage it must be readily dispersible with slight agitation so, as to ensure the uniformity of the dose. All the suspensions were found to be redispersible irrespective of their concentration.

CONCLUSION:

The preparations were assessed based on their sedimentation volume, viscosity, and flow rate analysis. The results showed that sedimentation volume, viscosity and particle size were found to be directly proportional to in view of these properties, mucilage of Leucaena latisiliqua gum can be employed as stabilizer and thickener of choice when high viscosity is desired especially in cosmetic, pharmaceutical and food industries.

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Received on 30.03.2009 Modified on 28.05.2009

Research J. Pharm. and Tech.2 (4): Oct.-Dec. 2009; Page 719-722