Suspensions are an important pharmaceutical dosage form that is still widely in use. Owing to their versatility they are often used in situations where the patients are unable to swallow tablets or capsules (Marriot et al.,  2010). Pharmaceutical suspensions are dispersions of an insoluble drug in an aqueous or non-aqueous continuous phase and like other disperse systems they are thermodynamically unstable. Thus, it is necessary to include in the dosage form a stabilizer or suspending agent. A well-formulated suspension should easily be re-suspended when moderately agitated and should allow uniform and accurate doses of the medicament to be withdrawn throughout the period of medication. Suspending agents are used in formulations to help the dispersed phase to remain suspended long enough when shaken and assist in easy re-dispersion of settled particles on standing (Ogaji, 2011). These have the benefit that consistent withdrawal of uniform doses is possible throughout the medication period. Natural gums from Irvingia gabonnsis, Albizia zygia, Grewia mollis and Khaya grandifolia have been reported to provide the needed platform for some of the quality attributes of a suspension due to their ability to swell when in contact with water and their viscous nature (Ndjouenkeu et al., 1996; Femi-Oyewo et al., 2004; Isimi et al., 2000; Ogaji, 2011; Nep and Conway, 2010). Natural gums are generally biodegradable, cheap, easily available, effective, and ecofriendly as compared to synthetic and semi-synthetic materials as pharmaceutical excipients (Prasad et al., 1998; Rana et al., 2011; Bakre and Abimbola, 2013).

 

Okra (Abelmuscus esculentus) is an annual or perennial herbaceous plant, growing up to 2 m tall straight up with very little phototropism. The pod could be green, red or purple, long, slender or chunky with numerous ridges running along the length of the pod. The pod varies in length from a few to about 7 cm in length and 1 to 4 cm in width. Okra plant grows very fast; therefore, it must be harvested every two days. Although, the crop can be grown on all soil types; sandy loam soils high in organic matter are the most desirable. Okra is among the most heat-and drought-tolerant vegetables in the world. Once established, it can survive severe drought conditions. The edible pods are used in soups and as a vegetable (Smith et al., 2002).

 

Chrysophyllum albidium fruit is almost spherical, with a slight point at the tip. There are 3 to 5 seeds brown, shiny seeds (1-1.5 × 2 cm), arranged in a star-shaped pattern in the yellow pulp. The seeds have a hard seed coat and the fruit turns from greenish grey when immature to orange, pink or yellow when ripe (Smith et al., 2002).

 

Although some works (Boyinbode and Iranloye, 1986; Odeku and Akinlosotu, 1997) had been carried out on the gums extracted from okra and C. albidium gums as excipients in pharmaceutical formulations, it appears that no work has been done to assess the suitability of these gums as suspending agents in paracetamol suspension as compared to the relatively common natural agents like gelatin and compound tragacanth gum. Paracetamol was chosen for this investigation because it is a practically insoluble drug which would require a suspending agent to be prepared as a liquid dosage form.

Materials

 

The materials used were paracetamol powder (Spectum chemicals, USA), benzoic acid, acetone (BDH Chemicals, UK), compound tragacanth gum (Searl Co., England), and gelatin (Merck, Germany). Water was double distilled and every other chemical was of analytical grade.

 

 

Extraction of gums

 

Okra gum was extracted from the pods of A. esculentus fruit using the method of Onunkwo and Mba (1996). The fruits were cleaned, washed, sliced, crushed and then macerated in distilled water for 10 h with intermittent stirring. The mucilage was filtered through a white muslin cloth to extract the gum and acetone was added to precipitate the extracted gum. The gum obtained labeled as AEG was then filtered under vacuum to remove acetone and dried in a dessicator. The same procedure was used for the extraction of gum from ripped (RCAG) and unripped (UCAG) C. albidium fruit.

 

 

Formulation of paracetamol suspension

 

A 0.5 g quantity of compound tragacanth powder and 5 g of paracetamol were triturated together with 50 ml of water to form a smooth paste. The mixture was transferred into a 100 ml of measuring cylinder 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 suspension contains 0.1% w/v benzoic acid as preservative. The procedure was repeated using 1.5, 2.5, 3.0, and 4.0 g of compound tragacanth powder. The aforementioned procedure was repeated with gelatin, okra and C. albidium gums

 

 

Phytochemical analysis

 

Phytochemical analysis was carried out following established procedures in the British Pharmacopoiea (1998).

 

 

Determination of sedimentation volume and rate

 

Each suspension (50 ml) was stored in a 50 ml measuring cylinder for 7 days at 35°C. Observations were made at every hour for 7 h and then every 24 h for 7 days. The sedimentation volume, F (%), was then calculated using the following equation.

 

F = 100 Vu/Vo             (1)

 

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

 

 

Rheological assessment using Brookfield viscometer

 

Viscosities of the prepared suspensions were determined using a Brookfield Synchro-electric viscometer; model LVF (Brookfield Laboratories,   Massachusetts).  Different    concentrations   of    the prepared suspensions were put separately in a 600 ml beaker, appropriate enough to immerse the spindle groove in the fluid. Viscosity values at rotational speeds of 10, 20, 50, and 100 rpm were determined at room temperature. All determinations were made in at least triplicate and the results obtained are expressed as the mean values.

 

 

Determination of flow rate

 

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

 

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

 

 

Ease of re-dispersibility of formulated suspensions

 

Fifty milliliters quantities of the formulated suspensions were poured into bottles, stoppered and kept on a vibration free platform. The suspensions were shaken 3 times, manually by hand after 7 days to find out how much of it was re-dispersed.

Phytochemical analysis of gums

 

Phytochemical tests carried out on RCAG and AEG gums confirmed the absence of alkaloids, anthraquinones and carbohydrates in accordance with the belief that gums do not contain carbohydrates, but complex acids built up of less common sugar (Femi-Oyewo et al., 2004).

 

 

Effects of various suspending agents on the sedimentation volume of paracetamol suspension

 

Table 1 shows the sedimentation volume of the paracetamol suspensions at 0 to 4.0% w/v suspending agents for 7 days. The internal phase settled rapidly within the first 1 h of preparation for suspensions containing RCAG and compound tragacanth and settled constantly over the next 7 days. Paracetamol suspension formulated with AEG exhibited the highest sedimentation volume while suspensions containing UCAG had the lowest sedimentation volume. High sedimentation volume is an indication that although the internal phase particles have settled, as would be expected with suspensions, the inter particle attraction and bonding were loose and not strong enough to form hard cake during the study period. The result suggested that differences in the sedimentation profiles was probably due more to the suspending agent used than the properties of  the internal phase. The rank order of the suspending ability of the suspendants as evaluated by the sedimentation volume was AEG > Gelatin > Compound Tragacanth > RCAG > UCAG.

 

 

Most pharmaceutically useful polymers contain polar functional groups that are separated by a hydrocarbon backbone. This structure provides the polymer molecule with many active centres that permit interaction with a particle surface. At very low concentration of polymer, a large number of sites on the surface of the dispersed solids are available for adsorption of the polymer. The simultaneous adsorption of the polymer molecule on to the surfaces of different particles creates a bridge. At a high concentration of polymer, there is complete coverage of the particles by the polymer and insufficient binding sites remain on the particles to form interparticulate bridges. This consequently leads to deflocculation due to formation of adsorbed layers of polymer on different particles (Gennero, 2000). Generally, at higher gum concentration of 3.0 and 4.0% w/v, it was observed that the suspensions showed low sedimentation volume.

 

 

Effects of types of suspending agents and concentrations on the viscosity, flow rate and re-dispersibility of paracetamol suspension

 

The viscosity of suspensions is a factor of great importance for stability and pourability of suspensions. Suspensions are the least stable dosage form due to sedimentation and cake formation. The viscosity of different concentrations of the test gums are as shown in Table 2.

 

 

formulated with RCAG have comparative viscosity with those containing gelatin and compound tragacanth. However, paracetamol suspensions containing AEG have significantly higher viscosity (p<0.05) than those containing RCAG, gelatin and compound tragacanth. This suggests that paracetamol suspensions formulated with AEG have a low terminal settling velocity; thus, the dispersed phase settles at a slower rate and remains dispersed for a longer time yielding higher stability to the formulated suspension. As the concentration of the gum increases, the viscosity of the paracetamol suspension increases. This suggests that paracetamol suspension with higher gum concentration is expected to give a suspension that settles slowly. The flow rate decreases with increase in the concentration of the suspending agent and increase in the viscosity. Paracetamol suspension containing RCAG and UCAG were easily re-dispersible with minimum agitation and are stable enough for adequate dose withdrawal.

 

 

Effect of speed of rotation on the viscosity of gums

 

Figure 1 shows the effect of speed of rotation on the viscosity of paracetamol suspension formulated with 1.5% w/v concentrations of test gums.

 

 

The decreased viscosity values observed with increasing speed of rotation for formulations containing AEG could be attributed to the nature of the mixture which may likely be pseudoplastic. This implies that with minimum agitation the suspension will be easily re-dispersed and a stable dose can be withdrawn. However, the viscosity of formulations containing RCAG, UCAG, gelatin and compound tragacanth was proportional to the speed of agitation

On the basis of these findings, A. esculentus and C. albidium may find application as suspending agents in pharmaceutical suspensions for pediatric and geriatric patients

The authors declare that they have no conflict of interests.

The authors acknowledge the Department of Pharma-ceutics and Pharmaceutical Technology, Olabisi Onabanjo University for the use of its laboratory facilities.