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الموضوع: صيدلانيات

  1. #1

    افتراضي صيدلانيات

    ارجو المساعدة جزاكم الله خير ويوفقكم دنيا والاخرة
    عند اختبار بكرة صيدلانيات وانا مافهم شى لان الدكتور يشرح شرح حتى المتخرجين مايفهمون
    وهذة المذكرات(مادري وشئ اذاكر لاني باقي المستوى3)
    الجزء1





    nSUSPENSIONS

    nDefinition:
    n Suspension means the dispersion of finely divided, insoluble solid particles (the dispersion phase) in a fluid (the dispersion medium). Most of the pharmaceutical suspensions consist of an aqueous dispersion medium, or it may be organic or oily liquid.
    nThere are two types or suspensions:
    nColloidal suspension: when the mean particle diameter of the dispersed phase is up to 0.5 µm.
    nCoarse suspension: when the particles are above colloidal size (i.e. above 0.5µm)

    nPhysical properties of a well-formulated suspension:

    n1-The suspension must remain sufficiently homogenous for at least the period between shaking the container and removing the required dose.

    n2-The sediment product on storage must be easily resuspended by agitation.



    n3-If the suspension required to be thickened; its viscosity must not be so high that removal of the doses from the container and transfer to the sits of application is difficult.

    n4-The suspended particles should be small and uniformly sized in order to give a smooth, elegant product free from gritty texture.

    nPharmaceutical application of suspension:

    n1) If the drug is insoluble or poorly soluble in a suitable solvent then formulation is usually required to be in suspension.

    nExample: eye drops of hydrocortisone and neomycin are available as suspension because of their poor solubility in a suitable solvent.



    n2) The degradation of drug may occur in the presence of water, so, it may be possible to synthesize an insoluble derivative which can be prepared as suspension.

    nExample:OxytetracyclineHCl could be prepared by suspending its calcium salt in a suitable aqueous vehicle.




    n3) Drugs which degrade in aqueous medium may be suspended in non-aqueous vehicle.

    nExample:Phenoxymethylpenicilline is suspended in coconut oil and also, tetracycline HCl in the same base for ophthalmic use.


    n4) Prolonged contact between the solid drug particles and the dispersion medium can be reduced by preparing the suspension prior to administration.

    nExample:Ampiciline is provided by the manufacturer as the base or the trihydratemixed with the other ingredients. The pharmacist adds water immediately before use. The suitable shelf life is about 7 days at room temperature, and 14 days in a refrigerator.


  2. #2

    افتراضي

    n5) Some materials are required to be present in the GIT in a finely divided form, and their formulation as suspension will provide the desired high surface area.

    nExample:Kaolin, Mg. carbonate and Mg. trisilicate which are used for the adsorption of toxins and to neutralize hyperacidity.



    n6) The taste of drug is more noticeable if in solution than if in a suspension.

    nExample:Paracetamol suspension is more palatable than Paracetamol Elixir BP, and, also, chloramphinicol mixture in suspension are more palatable than solution.



    n7) Suspension of drug can be formulated for topical application.

    nExample:Calamine Lotion BP, which leaves a light deposit of the active agent on the skin after the evaporation of the dispersion medium.



    n8) Suspension can also be formulated for parenteral administration, in order to control the rate of absorption of the drug.

    nThe drug may be suspended in fixed oil, such as arachis or sesame oil, and after injection, it is present in the form of oil globule in the tissue fluid forming a small surface area for drug release.



    n9) Vaccines, which are used for the induction of immunity, are often formulated as suspension.

    nExamples:
    n A-Dispersion of killed microorganisms, as in Cholera Vaccine.
    n
    n B-The constituent toxoids, adsorbed on aluminium hydroxide, as in diphtheria and tetanus vaccine.


    n10) Some X-ray contrast media are formulated in suspensions.
    Examples:
    n1- Barium sulphate, for examining the alimentary tract for rectal or oral administration.
    n2- Propyliodone, dispersed in water or arachis oil for examining the bronchial tract.
    nFormulation of Suspensions

    n1) Particle size control:
    n The drug to be suspended must be finely subdivided prior to formulation as the rate of sedimentation of a suspended particle can be retarded by reducing its particle size.
    n Large particles (more than 5µm) give a gritty texture to the product and may cause irritation if injected or instilled into the eye. The ease of administration of a parenteral suspension depends upon particle size and shape. If the particle size is over 25 µm it may block the needle especially if they are acicular in shape rather than isodiametric.

    2) The use of wetting agents:
    n Insoluble solids may be:
    n1- easily wetted by water and will disperse readily throughout the aqueous phase with minimum agitation, or
    n2- exhibit hydrophobicity and not easily wetted, some of which form large porous clumps within the liquid, while the others remain on the surface and attached to the upper part of the container. This may be due to the interfacial surface tension between the solid and the liquid.The wetting agent reduces this effect and displaces the adsorbed air on the surface of the particles by the liquid.
    nSome of the most widely used wetting agents in pharmacy:

  3. #3

    افتراضي

    nSome of the most widely used wetting agents in pharmacy:

    nA) Surface active agents (Surfactants):
    nSurfactants would project into the aqueous medium becoming hydrated. Thus wetting of the solid would occur due to a fall in interfacial tension between the solid particles.

    Examples: Most surfactants are in 0.1% as wetting agents.
    n-The polysorbates (Tweens) and Sorbitan esters (Spans), for oral use.
    n-Sodium laurylsulphate and sodium dioctylsulphosuccinate for external applications.

    nB) Hydrophilic colloids:
    nThese materials behave as protective colloids by coating the solid hydrophobic with a multimolecular layer. This will impart a hydrophilic character to the solid and thus promote wetting.

    nExamples:acacia, bentonite, tragacanth, alginates and cellulose derivatives.

    C) Solvents :
    n Water miscible materials will reduce liquid /air interfacial tension and will penetrate the loose agglomerates of powder displacing the air from the pores of the individual particles thus enabling wetting to occur by the dispersion medium.

    nExample:alcohol, glycerol and glycols.
    nFlocculation or Deflocculation:

    n Suspensions may be flocculated or deflocculated depending on the forces of repulsion and the forces of attraction between the particles. In the deflocculated suspensions; the dispersed particles remain as discrete units and, since the rate of sedimentation depends on the size of each unit, settling will be slow. The repulsive forces between individual particles allow them to slip over each other. The slow rate of settling prevents the entrapment of liquid within the sediment which thus becomes compacted and very difficult redisperse. This phenomenon is called caking or claying, and is the most serious problems of physical stability of suspension formulation.



    n In the flocculated system, aggregation of particulars will lead to much more rapid rate of sedimentation because each unit (or aggregate) is composed of many individual particles and is therefore larger. The rate also depends on the porosity of aggregates since, if porous, the dispersion medium can flow through and around each aggregates of floccule as it sediment.





    nThe sediment of the flocculated system: consists of aggregates, each of them entraps a large amount of the liquid phase. These aggregates produce Looseor"fluffy" floccules of higher porosity with large volume and will easily redisperse by moderate agitation. The fast sedimentation rate, thus a danger of inaccurate dosing may occur, and also the product may look inelegant.



    nThe slow sedimentation of deflocculates system enabling uniform dosing but after settling, sediment is compact and difficult to residperse. An ideal situation could be obtained by preparing deflocculated system with a sufficiently high viscosity to prevent sedimentation.
    nFlocculating agents:

    n1) Electrolytes: the addition of an inorganic electrolyte to an aqueous suspension will alter the zeta potential of the dispersed particles and if this value is lowered sufficiently then flocculation may occur.

    nExample:sodium salts of acetates phosphates and citrates.



    n2) Surfactants: both ionic and non ionic surfactants have been used to bring about flocculation of the particles in suspension. Ionic surfactants may cause deflocculation by neutralization of the charge on each particle. Non-ionic surfactants may be adsorbed onto more than one particle and produce flocculated system at the appropriate concentration.

    n3) Polymeric flocculating agents: Polymers can be used to control the degree of flocculation. Their linear chain molecules form a gel-like network within the system and become adsorbed on to the surfaces of the dispersed particles thus holding them in a flocculated system.
    nExample:starch, alginates, cellulose derivatives, tragacanth, Carbomers and silicates.

  4. #4

    افتراضي

    Viscosity modifiers

    1) Polysaccharides:
    a) Acacia gum (gum Arabic), Tragacanth, Alginates (eg. Sodium alginate), or Starch (eg. Sodium starch glycollate; Explotab, Primojel, is a derivative of potato starch used for the extemporaneous preparation of suspension, and also as disintegrant).

    b) Water soluble cellulose: (eg. Methyl cellulose, Hydroxyethylcellulose, Sodium carboxymethylcellulose or Microcrystalline cellulose, Avicel)



    2) Hydrated silicates: (Bentonite, or Magnesium aluminium silicate ,Veegum):

    3) Carboxypolymethylene: (Carbopol)

    4) Colloidal silicon dioxide: ( Aerosil, Cab-O-sil )
    Formulation additives


    1) Buffers:
    The inclusion of buffers may be necessary to:
    a) maintain chemical stability,
    b) control tonicity, or,
    c) to ensure physiological incompatibility.


    2) Density modifier:
    If the disperse and the continuous phase have the some densities, sedimentation would not occur. Minor modification of the aqueous phase of a suspension, by adding sucrose, glycerol or propylene glycol; may prevent or modify the rate of sedimentation.



    3) Flavours, colours and perfumes:
    These materials may be useful to improve the attractiveness of the product: and to enable easy product identification.

    4) Humectants:
    These materials are sometimes incorporated at a concentration of about 5% into aqueous suspension for external application to prevent the product from drying out after application to the skin.
    Example:glycerol and propylene glycol.



    5) Preservatives:
    Preservatives may be added specially if naturally occurring materials to prevent the growth of microorganism. Care must be taken to ensure that no inactivation of the preservative occur due to interaction with other ingredients.



    6) Sweetening agent:
    High concentration of sucrose, sorbitol or glycerol, which will exhibit Newtonian properties, may adversely affect the rheological properties. Sweeteners may be salts and can affect the degree of flocculation.
    Stability testing of suspension

    The physical stability of a suspension is assessed by the measurement of these parameters:
    1) Its rate of sedimentation.

    2) The final volume or height of the sediment, and

    3) The ease of redispersion of the product.

    The first two parameters can be assessed easily by measuring the total initial volume of a suspension (Vo), and the volume or hight of the sediment (V), by plotting the value of V/Vo against time for a series of trial formulations, the slope of each line indicate which suspension shows the slowest rate of sedimentation.
    The value V/Vo becomes constant when sedimentation has seaced (or stopped).

  5. #5

    افتراضي

    nThe term flocculation value can be used which is a ratio of the final volume or height of the sediment of a flocculated systems to the volume or height of the fully sedimented cake of the same system which has been deflocculated.
    nβ = degree of flocc. (or Flocc.Value)
    nβ = Volume of Sediment of flocculate / Volume of Sediment of deflocculated
    nβ = 50/10 = 5.0

    nThe ease of redispersion of a system can be assessed qualitatively by simple agitations of the product.
    nCentrifugation:
    nThe process of centrifugation may destroy the structure of a flocculated system which may remain intact under normal storage conditions. The sediment formed would become tightly packed and difficult to redisperse wither the initial suspension is flocculated or deflocculated. This method gives a useful indication of the relative stability of a series of trial products.

    nTemperature cycling:
    n The physical stabilities of a series of suspension may be possible to be compared if subjected to raising of temperature under normal storage conditions.
    n Cycles consisting of storage for several hours at a temperature of about 40˚C followed by freezing have been used successfully.
    nManufacture of suspension

    n It is important to ensure, initially, that the powder to be suspended is in suitably fine degree of subdivision in order to ensure:
    na) minimum sedimentation rate, and,
    nb) adequate bioavailability.
    nPreparation of suspension on small scale:

    n The powdered drug can be mixed with the suspending agent and some of the vehicle using a pestle and mortar. A wetting agent, if necessary, may be added, at this stage, to aid dispersion. Other soluble ingredients should then be dissolved in another portion of the vehicle, mixed with the concentrated suspension and then made up to volume.
    nPreparation of suspension on large scale:
    n By making a concentrated dispersion of the suspending agent first by adding the material slowly to the vehicle while mixing, using suitable mixer, such as a propeller type blender or a turbine mixer. This stage is important as it ensure that agglomerates of the suspending agent are fully broken up. If the suspending agent is blended with one of the water soluble ingredients, such as sucrose, this will also, aid dispersion.

    nThe drug to be suspended is then added in the same way along with the wetting agent. Other ingredients should now be added, preferably dissolved in a potion of the vehicle, and the whole made up to volume.
    n Finally homogenization would ensure complete dispersion of the drug and the production of a smooth and elegant preparation. In normal cases, aqueous suspensions may be autoclaved for sterilization if the process dose not affects the physical or chemical stability.

  6. #6

    افتراضي

    السلام عليكم
    ربي يكون في العون
    انا عندي الاتنين امتحان صيدلانيات فاينال بس انا سنة اولى لكن المنهج بتاعك تماما يشبه منهجنا صيدلة فيزيائية ودكتورنا اجنبي وما بنفهم شئ منه

  7. #7
    تاريخ التسجيل
    Sep 2007
    الدولة
    Jordan & palestine
    المشاركات
    602

    افتراضي

    بالتوفيق يارب اخ الAMAF و pharmacy girl
    الماده واضحه وترتيبها تمام يعطيك العافيه على نقلها ..
    انت حاول افهمها فهم وبعدين احفظ الامثله والنقاط هيك بكون اسهل عليك
    تحياتي


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