Stability of suspensions
- 1. Stability of Suspensions Dr. kamal badr Nehal Abdelmoneim Elsayed Hadeer Rabeaa Kamal Marten Shenoda Aya Musa Ammar Rehab Abd Elmohsen Marwa Ahmed Mohammed
- 2. Introduction • A Pharmaceutical suspension is a disperse system in which internal phase is dispersed uniformly as finely divided insoluble particles throughout the external phase. • The internal phase consisting of insoluble solid particles having a specific range of size which is maintained uniformly throughout the suspending vehicle with aid of single or combination of suspending agent. • The external phase (suspending medium) is generally aqueous in some instance, may be an organic or oily liquid for non oral use.
- 3. Pharmaceutical Applications of suspensions Suspensions may be used pharmaceutically for anumber of reasons. Some are given bellow; Suspension is usually applicable for drug which is insoluble or poorly soluble. E.g. Prednisolone suspension To prevent degradation of drug or to improve stability of drug. E.g. Oxytetracycline suspension To mask the taste of bitter or unpleasant drug when formulated in solution form. Drugs are formulated in as suspesnion which will be more palatable E.g. Chloramphenicol palmitate suspension Suspension of drug can be formulated for topical application e.g. Calamine lotion.
- 4. Pharmaceutical Applications of suspensions Suspensions may be used pharmaceutically for anumber of reasons. Some are given bellow; Suspension is usually applicable for drug which is insoluble or poorly soluble. E.g. Prednisolone suspension To prevent degradation of drug or to improve stability of drug. E.g. Oxytetracycline suspension To mask the taste of bitter or unpleasant drug when formulated in solution form. Drugs are formulated in as suspesnion which will be more palatable E.g. Chloramphenicol palmitate suspension Suspension of drug can be formulated for topical application e.g. Calamine lotion.
- 5. Stability of suspensions • Factors that contribute to appreciable stability of a suspension include: • a)Small particle size- reduse the size of the dispersed particle increases the total surface area of the solid. The greater the degree of subdivision of a given solid the larger the surface area. The increase in surface area means also an increase in interface between the solids and liquids leading to an increase in viscosity of a system.
- 6. Stability of suspensions B) Increasing the viscosity • increasing the viscosity of the continuous phase can lead to the stability of suspensions. This is so because the rate of sedimentation can be reduced by increase in viscosity. Viscosity increase is brought about by addition of thickening agents to the external phase. In water these must be either soluble or swell. It is important to note that the rate of release of a drug from a suspension is also dependent on viscosity. Of a product. The more viscous the preparation, the slower is likely to be the release of a drug. Sometimes this property may be desirable for depot preparations.
- 7. Stability of suspensions C).TEMPERATURE. • Another factor which negatively affects the stability and usefulness of pharmaceutical suspensions is fluctuation of temperature. Temperature fluctuations can lead to caking and claying.
- 8. Viscosity of Suspensions • Viscosity of suspensions is of great importance for stability and pourability of suspensions. As we know suspensions have least physical stability amongst all dosage forms due to sedimentation and cake formation. • So as the viscosity of the dispersion medium increases, the terminal settling velocity decreases thus the dispersed phase settle at a slower rate and they remain dispersed for longer time yielding higher stability to the suspension. • On the other hand as the viscosity of the suspension increases, it’s pourability decreases and inconvenience to the patients for dosing increases. • Thus, the viscosity of suspension should be maintained within optimum range to yield stable and easily pourable suspensions.
- 9. Surfactants • Surfactants decrease the interfacial tension between drug particles and liquid and thus liquid is penetrated in the pores of drug particle displacing air from them and thus ensures wetting. • Surfactants in optimum concentration facilitate dispersion of particles. Generally we use non-ionic surfactants but ionic surfactants can also be used depending upon certain conditions. • Disadvantages of surfactants are that they have foaming tendencies. • Further they are bitter in taste. Some surfactants such as polysorbate 80 interact with preservatives such as methyl paraben and reduce antimicrobial activity.
- 10. Hydrophilic Colloids • Hydrophilic colloids coat hydrophobic drug particles in one or more than one layer. This will provide hydrophillicity to drug particles and facilitate wetting. • They cause deflocculation of suspension because force of attraction is declined. • e.g. acacia, tragacanth, alginates, guar gum, pectin, gelatin, wool fat, egg yolk, bentonite,Veegum, Methylcellulose etc.
- 11. Solvents • The most commonly used solvents used are alcohol, glycerin, polyethylene glycol and polypropylene glycol. The mechanism by which they provide wetting is that they are miscible with water and reduce liquid air interfacial tension. Liquid penetrates in individual particle and facilitates wetting. • Co-solvents Used in suspensions • Some solvents which themselves have high viscosity are used as co- solvents to enhance the viscosity of dispersion medium: • Glycerol, propylene glycol, sorbitol.
- 12. Mixing procedures the dispensing of suspensions • The method of dispensing suspensions is the same for most, with some differences for specific ingredients. • Crystalline and granular solids should be finely powdered in the mortar.The suspending agent should then be added and mixed thoroughly in the mortar. Do not apply too much pressure, otherwise gumming or caking of the suspending agent will occur and heat of friction will make it sticky. • Add a little liquid vehicle to make a paste and mix well until smooth and free of lumps. Continue with gradual additions until the mixture can be poured into a bottle. Further liquid is used to rinse all the powder into the bottle where it is made up to volume. • When water is prescribed as a vehicle, use freshly boiled and cooled water or potable water where permissible
- 13. Variations • If the wettinng agents are included in the formulation, add them before forming the paste • If syrup and/or glycerol are in the formulation, use this rather than water to form the initial paste • If soluble solids are being used, dissolve them in the vehicle before or after making the paste • Leave addition of volatile components, colouring or concentrated flavouring tinctures such as chloroform spirit, liquid liquorice extract and compound tartrazine solution until near the end