The ingredients employed in suspensions vary as per the nature of the drug, ie diffusible or indiffusible. Suspensions containing indiffusible solids require thickening agents Suspensions for internal use are mostly aqueous, whereas, for other routes it may be aqueous non-aqueous, hydroalcoholic or oily.
Drug- The drug should have minimum solubility, maximum chemical stability and good wettability in the vehicle. Drugs with some solubility in the vehicle, could result in the growth of crystals due to fluctuations in storage temperatures.
Preparation of suspensions in pharmaceutics containing diffusible solids is less complex than that of the Those with indiffusible solids. Incorporation of suspending agent latter type may lead to problems such as, adsorption of flavours and preservatives, unpourability, etc.
The drug particles are also generated by chemical reaction or by precipitation eg Blight milk of magnesia. The precipitation is done either by change in solvent or the pH of solvent of some systems. The precipitate formed should not be too fluid or too gelatinous. Rarely, active Reducing ingredients used in suspensions not in solid state, but it requires to be produced in suspension piacim form, eg. volatile oils in inhalations in such cases, a suitable excipient is required for unifam distribution of such volatile oils.
Drug, should have pleasant organoleptic properties. Drugs in insoluble state have less objectionable taste than their solution.
Ingredients used in formation of suspension -
Additives,
structured vehicle is included in the formulation of a suspension in order to (pdf)
1) Vehicle: Water is the choice of vehicle for oral liquids. Syrup, sorbitol, glycerin are usually used with water either to impart body to the preparation, as anti-gelling agents, or to improve palatability of the preparation. The added co-solvents or pH of system should not change the solubility of the drug in the vehicle. Suspensions administered by routes other than oral route may contain other non-aqueous or oily vehicles Calamine lotion is official in two forms, aqueous form and oily form.
2) Wetting Agents : Some insoluble drugs do not wet readily with water and their lumps float on the surface of the liquid. This poor wetting is attributed to the presence of entrapped air on the surface of solid. To ensure satisfactory wetting and escape of entrapped air from liquid preparations, the solid-liquid interfacial energy must be reduced; and for this purpose, surfactants having HLB 7-9 are useful in concentrations up to 0.1 per cent. For oral administration, of non-ionic surfactants, used externally, quillaia tincture and sodium lauryl sulphate are used. The second approach is Solid levigation. Glycerin, propylene glycol, sorbitol are Figure 12.2: Mechanism of Levigation valuable levigating agents. These viscous solvents flow into the voids/pores of the particles to displace air. e.g. sulphur lotion contains quillaia incture, alcohol and glycerin to increase wettability of precipitated sulphur. Hydrocolloids, such as acacia, tragacanth and sodium alginate forms hydrophilic coat on the surface of hydrophobic particles.
3) Suspending Agents: Suspending agents act mainly by increasing the viscosity of external phase, thus reducing the rate of sedimentation of dispersed particles. In addition, some suspending agents also form a protective coat around the individual particles, making them less sensitive to electrolyte concentration. Hydrocolloids like acacia, tragacanth, and cellulose increase the viscosity of water by binding water molecules and thereby limiting their mobility and fluidity. Many of them are protective colloids in low concentration (<0.1 per cent) and viscosity enhancers in relatively high concentration. Suspending agents are selected on the basis of viscosity thus produce.
Types of Suspending Agents
1) Natural suspending agents (Natural hydrocolloids)
1) Acacia : Acacia is usually used as mucilage, which is 35 per cent dispersion of acacia water. It increases viscosity of the water phase. Secondly, it is less sensitive to elect concentration and forms protective coat around the dispersed particles. It is sticky to be alone, and is thus, usually is combined with tragacanth. The viscosity of acacia solution maximum between pH 3-9. Acacia is suitable for use in mixtures containing alcohol up to 25 per cent. Acacia often has high microbial count, therefore, use of preservative is necessar It also contains a peroxidase enzyme which causes oxidation of oxygen-sensitive d Heating the acacia mucilage for a few minutes at 100°C destroys the peroxidase enzymes.
2) Tragacanth: Tragacanth in 6 per cent concentrated mucilage is employed in quantes to 10 ml/100 ml of mixture. It produces a viscous, but less sticky preparation Viscosity solution increases to maximum after several days. Tragacanth mucilage is effective smaller ofrange pH 4 to 6. Like acacia, it is suitable for use in mixtures containing alcoho to 35 per cent of the total volume. Advantage of tragacanth over acacia is its effectivene lesser amounts and it is free from the oxidase enzyme. Since material is from a natural sour preparations containing tragacanth require inclusion of preservative.
3) Starch: Starch mucilage is 2.5 per cent starch in water and it is used as ingredients
compound powder of tragacanth.
4) Compound powder of tragacanth (CPT): It is a mixture of 20 per cent of powdered acacia, 15 per cent of tragacanth, 20 per cent of starch and 45 per cent of sucrose. It has combined properties of all ingredients and used in quantities of 2 g/100 ml of mixture. 5) Sodium alginate Sodium alginate forms a viscous colloidal solution with water. To avoid lump formation, sodium alginate should be wetted with alcohol, glycerin or propylene glycol and then mixed with water, using high speed mixer. It is stable in pH range of 4-10 and possesses maximum viscosity at pH 7.
6) Clays Clays are naturally occurring minerals. Bentonite, hectorite and veegum are the different clays used as suspending agents. Bentonite is natural colloidal hydrated aluminum silicate. It hydrates readily, absorbing many times of their volume of water and swell up to about twelve times its original volume. 5per cent dispersion is generally used suspending agent. Hectorite absorbs more water than bentonite does and exhibits thixotropy. Properties of Veegum are intermediatery between bentonite and hectorite.
The pH of aqueous clay dispersion is somewhat alkaline in nature and they are most stable between pH 9 and 11. Clays require adequate preservation and non-ionic preservatives are most suitable.
I) Semi-synthetic suspending agents
1) Methyl cellulose (MC): Methyl cellulose is soluble in cold water, but insoluble in hot water. It can be used in mixtures containing 70 per cent alcohol, Methyl cellulose is resistant to bacterial attack.
2) Sodium Carboxymethyl cellulose (Sodium CMC): It is soluble in both cold and hot water. Sodium CMC is generally used in 0.25 to 1 per cent concentration as suspending agent. Being anionic, it is incompatible with cationic compounds. It can tolerate alcohol concentration upto 50 per cent.
3) Hydroxyethyl cellulose (HEC): It is soluble in both cold and hot water. It can be used successfully in mixtures containing alcohol upto 80 per cent.
4) Microcrystalline cellulose (MCC): MCC disperse readily in water to produce thixotropic gels.
Ill) Synthetic suspending agents
1) Carbopols: Carbopols are synthetic, high molecular weight carboxyvinyl polymers. Thus dissolve in water and the dispersion is acidic in nature. Its advantage as a suspending agent is its effectiveness in low concentration, resistant to microbial attack and uniformity in composition.
2) Colloidal silicon dioxide: It is used in concentration of 1.5 - 4 per cent to stabilise
suspensions.
4) Density Modifiers: Ideally, the density of suspended phase and medium should be equal. Although it is difficult, the density of vehicle can be increased by replacing water totally or partly with syrup, sorbitol, etc.
5) Preservative: Preservatives employed in suspensions are the same as that of monophasic liquids. However, suspended particles with high surface-free energy may adsorb preservatives, e.g. benzalkonium chloride adsorbed by kaolin.
6) Organoleptic Additives Flavouring agents, colours and sweeteners are selected in association with each other on the basis of the age of the patient and the route of administration Both dyes and lakes, are used in combination to overcome limitations of individual. The other selection criteria are the same as that for monophasic liquids.
Examples of suspending agents:-
For definition and classification of pharmaceutical suspension,
Advantages and disadvantages of suspension, formulated and Defocculated suspension. Click on above link. Thank you.
Comments
Post a Comment