Introduction:

Aluminum hydroxide is proved to be used to provide symptomatic relief

in gastric and duodenal ulcer and in reflex oesophagitis, and in treatment

of hyperchlorhydria. It exerts its antacid action by reaction with

hydrochloric acid resulting in the formation of aluminum chloride which,

further, reacts with alkaline secretion of the intestine to for basic

aluminum salts.

Aluminum hydroxide proved to be one of the most efficient antacids.

It is available in USA market under the names of Amphojel, Alternagel,

Gallipet and Riopan.

Aim:

To develop a suitable formula of flocculated aluminum hydroxide

suspension for relief of hyperacidity and to some extent for treatment of

gastric and duodenal ulcer.

Objective:

-To prepare flocculated aluminum hydroxide suspension.

-To check the stability of the prepared aluminum hydroxide suspension.

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Statements of problem:

Aluminum hydroxide suspension constitute a problem in formation of

deflocculated suspension such deflocculated suspension cause inaccuracy

of dosage and instability of the product.

Thus it seems to prepare a flocculated suspension of aluminum

hydroxide.

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Review of literature

Suspensions:

Suspensions may be defined as preparations containing finally divided

drug particles (the suspensoid) distributed somewhat uniformly

throughout a vehicle in which the drug exhibits a minimum degree of

solubility. Some suspensions are available in ready-to-use form that is,

already distributed through a liquid vehicle with or without stabilizers

and other additives.

Reasons of suspension:

There are several reasons for preparing suspension. For one thing, certain

drugs are chemically unstable in solution but stable in suspension. For

many patients, the liquid form is preferred to the solid of the same drug

because of the ease of swallowing liquids and flexibility in of

administration of a range of doses. Thus particularly for infants, children,

and the elderly. The disadvantage of a disagreeable taste of certain drugs

in a solution form is overcome when the drug is administered as

undissolved particles of an oral suspension.

Features desired in a pharmaceutical suspension:

There are many considerations in the development and preparation of a

pharmaceutically elegant suspension. In addition to therapeutic efficacy,

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chemical stability of the components of the formulation, permanency of

qualities in all pharmaceutical preparations – a few other features apply

more specifically to the pharmaceutical suspension:

1. A properly prepared pharmaceutical suspension should settle slowly

and should be readily redispersed upon gentle shaking of the container.

2. The particle size of the suspensoid should remain fairly constant

throughout long period of undistributed standing.

3. The suspension should pour readily and evenly from its container.

This main features of a suspension, which depend on the nature of the

dispersed phase, the dispersion medium, and pharmaceutical adjunct.

Deflocculated suspension:

If a suspension is deflocculated the dispersed particles remain as discrete

units and, since the rate of sedimentation depends on the size of each

units, settling will be slow. The repulsive forces between individual

particles allow them to slip past each other as they sediment. The slow

rate of settling prevents the entrapment of liquid within the sediment

which becomes composed and can be very difficult to redisperse. This

phenomenon is also called caking or claying and is the most serious of all

the physical stability problems encountered in suspension formulation.

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Flocculated suspension:

Aggregation of particles in a flocculated system will lead to a much more

rapid rate of sedimentation or subsidence because each unit is composed

of many individual particles and is therefore larger. The rate of settling

will also depend on the porosity of the aggregate since, if porous, the

dispersion medium can flow through as well as round each aggregate or

floccule as it sediments.

From that of deflocculated one. The structure of each aggregate is

retained after sedimentation thus entrapping a large amount of liquid

phase. The volume of the final sediment will still be large and will easily

be redispersed by moderate agitation.

Preparations of suspensions:

In the preparation of suspension, the pharmacist must be acquainted with

the characteristics of both the intending dispersed phase and dispersion

vehicle to be employed and is readily wetted by it. Other drugs are not

penetrated easily by the vehicle and have attendency to clump together or

the float on the vehicle. In the later case, the powder must be wetted to

make it more penetrable by the desperation medium. Alcohol, glycerin,

propylene glycol and other hygroscopic liquids are employed as wetting

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agents when an aqueous vehicle is to be used as the dispersion phase.

They function by displacing the air in the crevices of the particles,

dispersing the particles, and allowing penetration of dispersion medium

into the powder. In large-scale preparation of suspensions the wetting

agents are mixed with the particles by an apparatus such as a colloid mill,

Once the powder is wet, the dispersion medium (to which have been

added all of the formulation's soluble components, such as a colorants,

flavorants, and preservatives) is added in portions to the powder, and the

mixture is thoroughly blended before subsequent additions of vehicle. A

portion of the vehicle is use to wash the mixing equipment free of

suspensoid, and ensure that the suspension contain the desired

concentration of solid matter. The final product is then passed through a

colloid mill and other blender or mixing device to ensure uniformity.

Antacid oral suspensions:

Antacids are intended to counteract the effects of gastric hyperacidity and

as such are employed by persons, such as peptic ulcer patients, who must

reduce the level of acidity in the stomach. They are also widely employed

and sold over the counter (OTC), to patients with acid indigestions, from

the stomach to the esophagus and take antacids to counter the acid in the

Most antacids preparations are composed of water-insoluble materials

that act within the gastrointestinal tract to counteract the acid and/or sooth

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the irritated or inflamed linings of the gastrointestinal tract. Example of

these materials salts of aluminum, calcium, and magnesium are

employed, these include aluminum hydroxide, aluminum phosphate,

dihydroxyaluminum, aminoacetate, calcium carbonate and calcium

phosphate, magnesium carbonate, and magnesium hydroxide. The ability

of each of these to neutralize gastric acid varies with the chemical agent.

For instance magnesium carbonate and magnesium hydroxide neutralize

acid effectively, whereas magnesium trisilicate and aluminum hydroxide

do 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. Each agent has its own peculiar

potential for adverse effect, for example excessive use of aluminum

hydroxide may lead to constipation and phosphate depletion with

consequent muscle weakness, bone resorption and hypercalciuria.

Aluminum hydroxide:

This compound is used as an antacid and it is available as Suspension,

Granule, Tablet, Chewable, Liquid, Tablet, Capsule, Liquid Filled

Capsule, Powder for Suspension, Powder, Effervescent, Tablet,

Effervescent, Tablet, and Extended Release Solution. It is available in

USA markets under the names of Amphojel, Alternagel and Riopan.

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Aluminum Hydroxide Suspention:

Identification:

Clear, white suspension, free from any foreign odour or taste.

Presentation:

200, 300, 500 and 600 mL glass or plastic amber bottles.

Mechanism of action:

The hydroxide reacts with excess acid in the stomach, reducing its

acidity. This decrease of acidity of the contents of the stomach may in

turn help to relieve the symptoms of indigestion, sour stomach, and

stomach ulcers. It is forms aluminum chloride; when this reaches the

intestine, the chloride is released and is reabsorbed. Aluminum hydroxide

raises the pH of gastric juice to about 4; it also adsorbs pepsin. It acts

gradually and it is affect continuous for several hours (there was

suggestion – no longer widely believed – that aluminum, if absorbed,

could be involved in the pathogenesis of Alzheimer's disease. In fact,

aluminum is said not to be absorbed to any significant extent during

administration of aluminum hydroxide, but some perhaps overly cautious

practitioners may prefer to use other antacid). Colloidal aluminum

hydroxide combined with phosphate in the gastrointestinal tract and the

increased excretion of phosphate in the feces that occurs results in

8
decreased excretion of phosphate via the kidney. This is important in the

management of patients with chronic renal failure).

Before Using:

Allergies:

Tell your doctor if you have ever had any unusual or allergic reaction to

medicines in this group or any other medicines. Also tell your health care

professional if you have any other types of allergies, such as to foods

dyes, preservatives, or animals. For non-prescription products, read the

label or package ingredients carefully.

Pediatric:

Antacids should not be given to young children (under 6 years of age)

unless ordered by their doctor. Since children cannot usually describe

their symptoms very well, a doctor should first check the child. The child

may have a condition that needs other treatment. If so, antacids will not

help and may even cause unwanted effects or make the condition worse.

In addition, aluminum-containing medicines should not be given to

premature or very young children because they may cause serious side

effects, especially when given to children who have kidney disease or

who are dehydrated.

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Geriatric:

Aluminum-containing antacids should not be used by elderly persons

with bone problems or with Alzheimer's disease. The aluminum may

cause their condition to get worse.

Pregnancy:

Studies on effects in pregnancy have not been done in either humans or

animals. However, there have been reports of antacids causing side

effects in babies whose mothers took antacids for a long time, especially

in high doses during pregnancy.

Breastfeeding:

Some aluminum-containing antacids may pass into breast milk. However,

these medicines have not been reported to cause problems in nursing

babies.

Side Effects:

• Bone pain.

• Constipation (severe and continuing).

• Feeling of discomfort (continuing).

• Loss of appetite (continuing).

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• Mood or mental changes.

• Muscle weakness.

• Swelling of wrists or ankles.

• Weight loss (unusual).

• Nausea.

• Vomiting.

• Constipation.

• Large doses can cause obstruction.

• Excessive doses or normal doses in patients with low phosphate

diets may lead to phosphate depletion accompanied by increased

resorption and urinary excretion of calcium with the risk of

osteomalacia.

• Osteomalacia, encephalopathy and dementia have occurred in

patients with chronic renal failure on high aluminum-dose as a

phosphate-binding agent.

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Special Precautions:

• In patients with chronic renal failure, hyperaluminaemia may

occur.

Hypophosphataemia may occur with prolonged administration of large

doses of aluminum-containing antacids (except aluminum-phosphate)

especially in patients with an inadequate dietary uptake of phosphorus.

• Laboratory Tests - Serum phosphate levels should be monitored at

monthly or bi-monthly intervals in patients on maintenance

haemodialysis who are receiving chronic aluminum hydroxide

therapy.

Drug interactions:

1. Renal impairment:

Aluminum is absorbed and may be accumulate.

2. Citrate:

Absorption of aluminum salts is increased by citrate, which are contained

in many effervescent preparations (such as effervescent analgesics).

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3. Folic acid:

Folic acid is needed by the body to utilize vitamin B12. Antacids,

including aluminum hydroxide, inhibit folic acid absorption. People

taking antacids are advised to supplement with folic acid.

4. Phosphorus:

Depletion of phosphorus may occur as a result of taking aluminum

hydroxide. For those with kidney failure, reducing phosphorus absorption

is the purpose of taking the drug, as excessive phosphorus levels can

result from kidney failure. However, when people with normal kidney

function take aluminum hydroxide for extended periods of time, it is

possible to deplete phosphorus to unnaturally low levels.

5. Calcium:

Aluminum hydroxide may increase urinary and stool loss of calcium.

Also, aluminum is a toxic mineral, and a limited amount of aluminum

absorption from aluminum-containing antacids does occur.

6. Deferasirox:

Aluminum hydroxide possibly reduce absorption of Deferasirox.

7. Thyroid hormone:

Possibly reduce absorption of levothyroxin.

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How should I take aluminum hydroxide suspension?

To ensure that you get the correct dose, measure the liquid form of

aluminum hydroxide with a dose-measuring spoon or cup, not a regular

table spoon. If you do not have a dose-measuring device, ask your

pharmacist where you can get one. Shake the suspension well before

measuring a dose. A dose of the liquid formulation can be followed with a

drink of water if you desire.

What happens if I miss a dose?

Take the missed dose as soon as you remember. However, if it is almost

time for the next dose, skip the dose you missed and take only the next

regularly scheduled dose. Do not take a double dose of this medication

unless otherwise directed by your doctor.

Overdose:

Seek emergency medical attention.

Symptoms of an aluminum overdose include weight loss, decreased

appetite, general feeling of sickness, muscle weakness, kidney failure,

and softening of the bones.

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Description of the proposal project:

Aluminum hydroxide constitute a problem in formulation including

tendency to form a deflocculated suspension, such deflocculated

suspension cause inaccuracy of dosage and instability of the product.

Thus, It seems important to prepare a flocculated aluminum hydroxide

suspension to relief hyperacidity and for treatment of ulcers, heartburn,

gastritis, peptic ulcer or dyspepsia acid reflux, acid indigestion, sour

stomach, and stomach ulcers.

The second thing in the project is checking the stability of the prepared

suspension by test of sedimentation ratio, flocculation, redispersability,

acid neutralizing capacity, rheological characters and extent of

flocculation.

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Methodology:

Identification of the type of surface charge of aluminum hydroxide

powder:

This is achieved by the preparation of aluminum hydroxide suspension

(10%w/v) in distilled water using different concentration of aluminum

chloride and potassium dihydrogen phosphate as flocculating agents. The

sedimentation volume, clarity of supernatant and degree of redispersion

of the prepared suspension were observed after 2, 15 and 30 days.

Preparation of the suspension:

Aluminum hydroxide powder (2.5g of 30u average particle size) were

levigated with each of the selected stabilizer as solution in a mortar and

the flocculating agent solution, if any, was added with trituration. The

suspension was diluted with distilled water, transferred to 25 ml glass

stoppered measuring cylinder, complete to volume with water with

shaking, stored at room temperature (20º± 5º), and examine at specific

time intervals for:

Sedimentation ratio:

Is the ratio between the height of the sedimented volume in ml (Hu)

and the original height of the sample column in ml (Ho).

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Flocculation:

Measure the degree of flocculation by three means:(1) the sedimentation

ratio, (2) examine the supernatant layer for evidence of opalescence

caused by small discrete particles settling slowly in deflocculated state

and (3) examine the sedimented particles under microscope where the

presence of sphere or agglomerated particles indicates flocculation.

Redispersability:

Determination of redispersion of the prepared suspension by upside down

inversions of the containing measures through an angle of 180º at a

constant speed of 20 inversions per minute. Record the number of

inversions that necessary to restore the suspension homogeneity.

Acid neutralizing capacity:

The best formulae proved to be physically stable were submitted for

determination of their acid neutralizing capacity relative to the plain

suspension (without adjuvants). This is carried by adopting the method

described by BP.

Extent of flocculation:

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The extent of flocculation will be determined by dividing the sediment

volume of the suspension to which the flocculating agent was added over

that without flocculating agent. Values greater than one indicates

flocculation and the larger the value, the more enhanced is the degree of

flocculation.

Rheological characters:

Examination for their flow behavior when fresh and after three months

storage using rotary viscometer at 25±1cº.

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Summary and Conclusion:

Development of a suitable formula of flocculated suspension of

aluminum hydroxide for treatment of hyperacidity.

19
References:

1. British pharmacopoeia commission. 1999. The requirement of third

edition.

2. V. T. Allen, Jr. G. Nicholas, and P. H. C. Ansel. Ansel's Pharmaceutical

dosage form and delivery systems. Eighth edition. 2005. Disperse system.

P. 387-401.

3. H. P. Rang, M. M. Dale, J. M. Ritter, and P. K. Moore. 2003. The

Gastrointestinal tract, Pharmacology. Fifth edition. P. 371.

4. British National Formulary (BNF). September 2007. P. 685, 765.

5. M. E. Aulton. 2002. Suspension, The science of dosage form design.

Second edition. churchill-livingstone, London p. 269-285.

6.

http://en.wikipedia.org/wiki/Antacid#Action_mechanism#Action_mecha

nism

7. http://www.drugs.com/mtm/amphojel.html

8. http://www.mayoclinic.com/health/drug-

information/DR602357#top#top

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9.

http://www.medicinenet.com/script/main/art.asp?articlekey=44655&page

=1#OtherUses

10. http://www.truestarhealth.com/Notes/2818004.html

11.

http://www2.mooremedical.com/index.cfm?PG=CTL&CS=HOM&FN=P

roductDetail&PID=5095

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