International Journal of Drug Development and Research

Key words

natural polysaccharide, suspending Agents, sedimentation volume, rheology, particle Size

INTRODUCTION

A pharmaceutical suspension, like other disperse systems, is thermodynamically unstable, thus, making 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 medium. Suspending agents are (i) inorganic materials, (ii) synthetic compounds, or (iii) polysaccharides. Natural gums like Acacia, Tragacanth, Khaya, and Karaya gum come under this category of polysaccharide (1-3). Gums have been wildly used as tablet binders, emulgents and thickeners in cosmetics and suspensions as film-forming agents and transitional colloids. In this study, above mentioned four polymers viz. tragacanth gum, gum acacia, tamarind gum and gelatin were studied as suspending agent in paracetamol suspension as compared to the relatively common suspending agents of inorganic and synthetic category, using sedimentation volume, rheology and particle size analysis as assessment parameters. As reported, tragacanth is the dried gummy exudation from Astragalus gummifer and other species of Astragalus (2). The gum is obtained through injury to the stem and is accumulated in the pith and medullary rays. In general, for most of the gums absorption of water causes the gum to swell and exude through the incision. Most of the gums consist of the calcium, magnesium and potassium salts of bassoric acid, known as bassorin. Most of them have been reportedly used as a suspending agent for insoluble powder, an emulsifying agent for oils, resin and a binding agent. Whereas, gelatin is derived from animal skin and is polysaccharide in nature which shows good suspending property. Paracetamol was chosen as a model drug for this investigation (1,3) because it is a typical representative of practically insoluble drugs which would require a suspending agent to be prepared as a liquid dosage form.

MATERIALS AND METHODS

The materials used include paracetamol (fine powder), gelatin, benzoic acid BP, and amaranth solution, chloroform water and raspberry syrup BP (RANKEM limited, New Delhi), Acacia gum powder, compound tragacanth powder (central drug house (P) LTD, New Delhi). Tamarind gum was extracted from the seed of Tamarindus indica.

Isolation of gum from Tamarind Seed: The crushed seeds of Tamarindus indica were soaked in water for 24 h, boiled for 1 h, and kept aside for 2 h for the release of gum into water. The soaked seeds were taken and squeezed in a muslin bag to remove marc from the filtrate. Then, to the filtrate, equal quantity of absolute ethyl alcohol was added to precipitate the gum. The gum was separated by filtration. The marc was not discarded but it was sent for multiple extractions with decreasing quantity of extracting solvent, i.e., water with the increase of number of extractions. The isolation was continued until the material was free of gum. The separated gum was dried in hot air oven at temperature 40?C. The dried gum was powdered and stored in airtight containers at room temperature (4, 5).

Preparation of suspension: For preparation of paracetamol suspensions, polysaccharide powder (individually 0.5 g) and 10 g of paracetamol 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 bottle, made up to volume with distilled water and then shaken vigorously for 2 min (thus making 0.5%w/v of the gum in the preparation). The procedure was repeated using 1.0, 1.5, 2.0, 2.5, 3.0, 3.5 and 4.0%w/v of polysaccharide powder (4-6).

Sedimentation Volume: Each suspension (50 ml) was stored in a 50 ml-measuring cylinder for 7 days at 35oC. Observations were made at every hr for 7 hr and then every 24 hr for 7 days. The sedimentation volume, F (%), was then calculated using the following equation:

F = 100Vu/Vo (1)

Where, Vu is the ultimate volume of the sediment and Vo is the original volume of the suspension.

Rheology: The time required for each suspension sample to flow through a 10 ml pipette was determined and the apparent viscosity (one gm per cm per sec) was calculated using the equation:

Flow rate = Volume of pipette (ml) /Flow time (s) (2)

The viscosity (in poise) of the samples was determined at 25°C using the Brookfield Synchro-lectric viscometer, model LVF (Brookfield Laboratories, Massachusetts) at 30 revolutions per min (Spindle #4). All determinations were made in at least triplicate and the results obtained are expressed as the mean values (7-11).

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 1, 5, 10, 15, 20, 25 and 30 min. This was transferred into an evaporating dish and evaporated to dryness in an oven at 105°C and the residue weighed. The particle diameter (d in cm) was then calculated using the Stokes equation(7,10-14):

d = η h/(γs-γ0) gt (3)

Where, h is the distance of fall of the particle (cm), t is the time (s), η is the viscosity of the dispersion medium (poise), (γs-γ0) is the density gradient between the dispersed particles and the liquid (g cm-3) and g is the gravitational constant (cm s-2) (15-17).

RESULTS

The effects of the type and concentration of the suspending agents on sedimentation volume, viscosity and particle size can be enumerated with the help of tables given below (Table 1- 4).

A suspension containing Paracetamol as model drug was prepared in batches containing tamarind gum, compound tragacanth, acacia and gelatin as suspending agents (in the concentration range of 1,2,3,4,5,7% w/v). The preparations were evaluated on the basis of their sedimentation volume, flow rate, viscosity, and particle size analysis.

Flow rate at higher concentrations of each suspending agent shows the fact that Tragacanth Gum has very poor flow rate in formulated suspension using paracetamol as model drug (Table5) Inverse proportionality was thus obtained between sedimentation volume and flow rate. The flow rate was found to obey the following order Tamarind gum > Gelatin > gum Acacia > Tragacanth gum. The results also illustrated the fact that the sedimentation volume, viscosity and particle size (except the flow rate) were found to be directly proportional to the concentration of the suspending agent. Inverse proportionality was noticed between time for sedimentation and sedimentation volume.

DISCUSSIONS

As demonstrated by all the parameters evaluated, Tamarindus indica seed gum possesses least potential as a candidate to act as suspending agent as compared to Gelatin, Gum Acacia and Gum Tragacanth. The present study also indicates the fact that Tamarind Gum cannot be used as stabilizer and thickener of choice when products of low viscosity grade are desired to be employed especially in cosmetic, pharmaceutical and food industries. All the studies also reveal the fact that Tragacanth gum has a very high potential to be used as suspending agent, stabilizer and thickener in pharmaceutical formulations in varying range of concentrations. The other two i.e. Gelatin and gum Acacia show better chances to be used but, not as prominent as that of Tragacanth gum. Thus, it can be predicted on the basis of all previous studies and present research work that though all gums possess characteristics to act as suspending agent but, suspending ability may differ. The study also illustrates that though gums may act as suspending agent, there are other natural polymers like Gelatin which possess significant suspending property when formulated in form of suspension.

Conclusion

The results show the fact that sedimentation volume, viscosity and particle size were found to be directly proportional to the concentration of the suspending agents. The reverse case has been reported on flow rate parameter. Inverse proportionality was observed between the storage time on one hand and sedimentation volume on the other. All the formulations were observed to obey the Stoke’s law (Equation 3) when subjected to particle size analysis. The suspending ability of the suspendants (as evaluated by the above assessment parameters) were in the order of Tragacanth gum > Gum Acacia > Gelatin > Tamarind gum. Thus, Tragacanth gum appeared to exhibit the best suspendability of all the materials which were under investigation.

Acknowledgment

Authors are highly thankful to Department of Pharmaceutical Technology, M.I.E.T, Meerut; for providing all the necessary facilities and support at every hour of work.

Conflict of Interest

NIL

Source of Support

NONE

Tables at a glance

Table 1 Table 2 Table 3 Table 4 Table 5

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