INTRODUCTION:

A pharmaceutical suspension is a biphasic system composed of finely divided insoluble solid material suspended in a liquid medium. The average size of suspended particles ranges from 0.5 µm to 5 µm in most of the pharmaceuticals suspensions[1]. An acceptable suspension possesses certain desirable qualities, including the following. The suspended material should not settle rapidly; the particles that do settle to the bottom of the container must not form a hard cake, but should be readily redispersed into a uniform mixture when the container is shaken; and the suspension must not be too viscous to pour freely from the orifice of the bottle or to flow through a syringe needle. For Pharmaceutical purposes, physical stability of suspensions may be defined as the condition in which the particles do not aggregate and in which they remain uniformly distributed throughout the dispersion[2]^.

A pharmaceutical suspension, like other disperse systems, is thermodynamically unstable, thus, making it stable is 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[3]. Suspending agents may be inorganic materials, synthetic compounds and polysaccharides. The suspending agent works by increasing the viscosity of the liquid vehicle, and there by slowing down settling in accordance with Stokes Law. Commonly used suspending agents include materials like hydrophilic colloids, clays and few miscellaneous agents. 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 demands. In the present work we were using various suspending agents, with their different concentration such as gelatin, tragacanth and bentonite.

Most suspending agents perform two functions i.e. besides acting as suspending agent they also imparts viscosity to the solution. Suspending agents form film around particle and decrease inter-particle attraction. A good suspension should have well developed thixotropy. At rest, the suspension should be sufficiently viscous to prevent sedimentation and thus aggregation or caking of the particles. When agitated the viscosity should be reduced and provide good flow characteristics so that the suspension flows smoothly from the mouth of bottle.

Acacia, a natural material is often used as a suspending agent for preparation of suspensions. its value as a suspending agent is largely due to its action as a protective colloid. Acacia is not very effective for dense powders, and for these it is often combined with other thickeners such as tragacanth, starch and sucrose in compound tragacanth powder. Unfortunately, acacia mucilage becomes acidic on storage as a result of enzyme activity, and it also contains an oxidase enzyme which may cause deterioration of active agents that are susceptible to oxidation. This enzyme can, however, be inactivated by heat[4-7]. Because of the stickiness of acacia it is rarely used in preparations for external use. Another suspending agent, Tragacanth product will form viscous aqueous solutions. Its thixotropic and pseudoplastic properties make it a better thickening agent than acacia and it can be used both for internal and external products. Like acacia, it is mainly used for the extemporaneous preparation of suspensions with a short shelf-life. Tragacanth is stable over a pH range of 4-7.5 but takes several days to hydrate fully after dispersion in water. The maximum viscosity of its dispersions is not, therefore, achieved until after this time, and can also be affected by heating[8-12]. In the same series, Gelatin is a heterogeneous mixture of water-soluble proteins of high average molecular weights, present in collagen. The proteins are extracted by boiling skin, tendons, ligaments, bones, etc. in water.Type A gelatin is derived from acid-cured tissue and Type B gelatin is derived from lime-cured tissue.In the pharmaceutical industry, gelatin is used as a suspending agent, encapsulating agent, and tablet binder. Likewise, Bentonite is essentially highly plastic clay containing not less than 85% clay mineral, montmorillonite. Bentonite has high swelling properties along with good viscosity[13-18]. This property made Bentonite a suitable suspending agent. Guar gum a useful suspending agent, also called guaran, is a galacto mannan. It is primarily the ground endosperm of guar bean(Cyamopsis tetragonoloba). It is not affected by ionic strength or pH, It remains stable in solution over pH range 5-7.

We have prepared oral antacids suspension; antacids are weak bases that react with gastric hydrochloric acid to form salt and water. They are employed in the treatment of hyperchlorhydria and peptic ulcer, collectively known as acid-peptic disease. Antacid and radiopaque suspensions generally contain high concentration of dispersed solids. Most antacids preparations are composed of water-insoluble materials that act within the gastrointestinal tract to counteract the acid and/ or soothe the irritated or inflamed linings of the gastrointestinal tract. A few water soluble agents are employed, including sodium bicarbonate, but for the most part, water- insoluble salts of aluminium, calcium, and magnesium are employed; these include aluminium hydroxide, aluminium phosphate, dihydroxyaluminium amino acetate, calcium carbonate, calcium phosphate, magaldrate, magnesium hydroxide.

The ability of each of these to neutralize gastric acid varies with the chemical agent. For instance, sodium bicarbonate, calcium carbonate, and magnesium hydroxide neutralize acid effectively, whereas magnesium trisilicate and aluminium hydroxide do so less effectively and much more slowly. In selecting an antacid, it is also important to consider the possible adverse effects of each agent in relation to the individual patient[19]. Among various antacid we were selected calcium carbonate, because its reaction with HCL in the stomach is not as rapid as of sodium bicarbonate, and for this reason, it produces a more prolonged reduction in gastric acidity. It reacts in the stomach, and 1 g neutralizes 200 ml 0.1 N HCL.

CaCo₂+ 2HCl CaCl₂ + H₂O + CO₂

The calcium chloride is converted in the intestine to insoluble salts (carbonate and Phosphate) and calcium soaps[20]. On the basis of this work we observed that, among various suspending agent, which are mentioned in this article, gelatin is a better suspending agent in comparison to other at the optimum concentration that is 2 % w/v (Table 1) and hence we can conclude that the gelatin can be used as a suspending agent for various antacid formulations and we were given the surety that this article helps the researcher, when they work on antacid suspension and it is also helpful in large scale production of antacid suspension too.

MATERIAL AND METHOD:

Material:

The materials used include Calcium carbonate, bentonite, acacia, guargum, gelatin, and tragacanth are procured from (Loba chemical). All solvents used were of analytical grade.

Method of preparation:

2 gram of calcium carbonate was taken in a clean mortar and pestle and triturated well. Then a small quantity of water was added to make a paste like consistency and then more amount of water was added and triturated well and then it was transferred to clean 100ml measuring cylinder and made the volume up to 100ml with water. Similarly, calcium carbonate suspensions containing different concentration (1%, 1.5%, 2%) of suspending agents (acacia, tragacanth, guar gum, bentonite, gelatin) were prepared[21].

Rheology:

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

The viscosity (in poise) of the suspensions prepared with gum tragacanth, bentonite, gelatin, guar gum and acacia were determined at 25^◦C using Brookfield viscometer (Brookfield engineering laboratories, INC. USA) at 50 rpm by using spindle no.3. All determinations were made in at least triplicate and the results obtained are expressed in (table 1) as the mean values[22].

pH:

The pH of the suspensions was determined at intervals of one week for 14 days using pH meter (Neo chemiphar company)[23].

Degree of Flocculation:

The degree of flocculation was determined following the equation β= F/Fα, where F is the ultimate sedimentation volume in the flocculated suspension and Fα is the ultimate sedimentation volume in the deflocculated suspension[24].

Redispersibility

Redispersibility can be estimated by shaking the suspension with the help of a mechanical device, which simulates motion of human arm during shaking. Fixed volume (50 ml) of the each suspension was kept in calibrated tubes which were then stored at room temperature for various time intervals (5, 15, 25 days). At regular interval of 5 day, one tube was removed and shaken vigorously to redistribute the sediment and the presence of deposit if any is recorded[25].

Rate of separation:

The rate of separation of the suspensions were determined by keeping 50 ml portion of each suspensions in stoppered measuring cylinder and stored undisturbed at room temperature. The separation of clear liquid was noted at intervals of 5 d up to 45 d[26].

Sedimentation volume:

The sedimentation volume is ratio of the ultimate height (Vu) of the sediment to the initial height (Vo) of the total suspension as the suspension settles in a cylinder under standard conditions. It was determined by keeping a measured volume of the suspension in a graduated cylinder in an undisturbed state for a certain period of time and notes the volume of the sediment, the sedimentation volume, F (%), was then calculated using the following equation[27].

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

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 at 1, 5, 10, 20, and 30 min[28]. The particle diameter (d in cm) was then calculated using the Stoke’s equation:

Where, h is the distance of fall of the particle (cm), t is the time in (s), η is the viscosity of dispersion medium (poise), Ps – Po is the density between dispersed particles and the liquid (g/cm³), g is the gravitational constant (cm/s²).

Table 1 Observation of stability parameters of suspension using different suspending agent at different concentration

Suspending agent	Concentration (%)	Flow Rate (ml/sec)	Viscosity (poise)	PH	Sedimentation volume
Gelatin	1	0.83	0.065	7	0.20
Gelatin	1.5	0.71	0.09	6	0.58
Gelatin	2	0.33	0.15	7	0.78
Tragacanth	1	1	4.1	7	0.12
Tragacanth	1.5	0.66	6.0	8	0.18
Tragacanth	2	0.55	7.8	8	0.25
Bentonite	1	0.83	5.4	6	0.14
Bentonite	1.5	0.71	7.2	7	0.28
Bentonite	2	0.67	7.4	6	1.53
Acacia	1	1.25	1.25	7	0.10
Acacia	1.5	1	1.40	7	0.20
Acacia	2	0.83	1.59	7	0.18
Guar gum	1	0.47	1.11	7	0.18
Guar gum	1.5	0.33	2.39	6	0.28
Guar gum	2	0.014	5.23	6	0.34