Chap 14 dispersed systems

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Discussion on the 2 kinds of Disperse Systems 1. Suspensions 2. Emulsions. The principles of emulsification, types and examples of emulsifying agents used.

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  • Particle shape affects caking and product stability
  • GREENHOUSE EFFECT AND DESTRUCTION OF OZONE LAYER
  • COLD TEMPERATURE IS NECESSARY TO LIQUEFY THE GAS
  • See table14.6 page 424.
  • Chap 14 dispersed systems

    1. 1. Chapter 14:DISPERSE SYSTEMSAsst. Prof. MA. LOURDES L. MOJARES, R. Ph Faculty CEU School of Pharmacy
    2. 2. DISPERSE SYSTEMS: COMPONENTS DISPERSED PHASEThe undissolved or immiscible drug (suspensoid) distributed throughout the liquid vehicle. Also called the “internal phase”
    3. 3. DISPERSE SYSTEMS: COMPONENTS DISPERSION MEDIUMThe liquid vehicle, to which the insoluble drug is distributed. Also called “external phase”
    4. 4. DISPERSE SYSTEMS: COMPONENTS DISPERSING /SUSPENDING AGENTStabilizes the suspension, maintains the homogeneity of the internal and external phases, after agitation of the contents.
    5. 5. DISPERSE SYSTEMSRemember the“Shake Well” instruction beforeadministeringsuspensions / emulsions.
    6. 6. DISPERSE SYSTEMS PARTICLE SIZES Colloidal dispersions – 1 nm to 0.5 nm Coarse dispersions (suspensions and emulsions) – 10 um to 50 um Fine dispersions ( magmas and gels) – 0.5 um to 10 um
    7. 7. SUSPENSIONS: DEFINITION Disperse systems containing finely divided, insoluble drug particles (“suspensoids’) distributed somewhat uniformly throughout a liquid vehicle.
    8. 8. SUSPENSIONS: DEFINITION Ready to use liquid form (antacids and analgesics) Labeled as “Oral Suspension” Dry powders for Reconstitution (antibiotics and other drugs that are unstable in liquid form for longer time)
    9. 9. REASONS for SUSPENSIONS1. For improving product stability2. Ease of administration and flexibility in administration of a range of doses3. For masking unpleasant taste of
    10. 10. Features desired in Pharmaceutical Suspension1. Particles should settle slowly and should be readily re-dispersed upon shaking of the container.2. The particle size of the suspensoid should remain fairly constant throughout long periods of undisturbed standing.3. The suspension should pour readily and evenly from its
    11. 11. DISPERSED PHASE: PHYSICAL FEATURES Particle diameter is 1 to 50 m Particle size reduction is accomplished by:  Micropulverization – 10-50 m  Fluid energy grinding (jet milling or micronization) – under 10 m
    12. 12. SUSPENDING AGENTS: TYPES AND EXAMPLES1. HYDROPHILIC COLLOIDS Increase the viscosity of water by binding water molecules Support the growth of microorganisms Mostly anionic, except methylcellulose (neutral) and chitosan (cationic) Incompatible with quaternary antibacterial agents
    13. 13. HYDROPHILIC COLLOIDS: EXAMPLES Acacia –used as 35% mucilage; form colored complex with organic compounds due to peroxidase Tragacanth – used as 5% dispersion in water; does not contain peroxidase Methylcellulose (MC) Carboxymethylcellulose (CMC)
    14. 14. SUSPENDING AGENTS: TYPES AND EXAMPLES2. CLAYS Silicates that are anionic in aqueous dispersion Strongly hydrated Exhibit thixotropyBentonite (as 5% magma), Veegum
    15. 15. SUSPENDING AGENTS: TYPES AND EXAMPLES3. OTHER AGENTS Agar Chondrus(carrageenan) Gelatin Pectin Gelatinized Starch
    16. 16. TYPES OF SUSPENSION1. ORAL SUSPENSIONS Ready to use Dry powders for reconstitution Uses: Antacid,Anthelmintic, Antibacterial(see table 14.1 pp.390-391)
    17. 17. TYPES OF SUSPENSION2. SUSPENSIONS FOR INJECTION Particles must exhibit “SYRINGEABILITY” The product must have the ability to be successfully administered by a syringe and appropriate needle.
    18. 18. TYPES OF SUSPENSION3. OPHTHALMIC SUSPENSIONS Particle size must not exceed 10 microns
    19. 19. TYPES OF SUSPENSION4. SUSPENSIONS FOR TOPICAL USE Fine particles (impalpable) are desired to avoid grittiness when applied to the skin The smaller the particle size, the greater the covering and protective power of the preparation.
    20. 20. TYPES OF SUSPENSION3. OPTHALMIC SUSPENSIONS Particle size must not exceed 10 microns Particles must be “impalpable”
    21. 21. TYPES OF SUSPENSION4. SUSPENSIONS FOR TOPICAL USE Fine particles are desired to avoid grittiness when applied to the skin The smaller the particle size, the greater the covering and protective power of the preparation.
    22. 22. TYPES OF SUSPENSION 5. RECTAL SUSPENSIONS Barium Sulfate for Suspension, USP  May be employed orally or rectally for diagnostic visualization of the GIT.
    23. 23. TYPES OF SUSPENSION MesalamineSuspension (Rowasa)  For the treatment of Crohn’s disease, distal ulcerative colitis, proctosigmoiditis, and proctitis.  No longer commercially available but is compounded by pharmacist.
    24. 24. PREPARATION OF SUSPENSIONSI. WETTING OF PARTICLES  Wetting agents are employed for hydrophobic (non-wetting) powdersII. BLENDING OF ALL THE INGREDIENTS  All soluble components must have been dissolved in the dispersion medium
    25. 25. CLASSES OF SUSPENSION1. LOTIONS2. GELS3. MAGMAS AND MILKS4. MIXTURES
    26. 26. LOTIONS Suspensions for external application. A low to medium viscosity, topical product, intended to be applied on “unbroken” skin. Lotions have lower viscosity than Creams and Gels.
    27. 27. LOTIONS Prepared by: (1) Trituration method (2) By chemical reaction method
    28. 28. TYPES of LOTIONS MEDICATED LOTIONS1. Kwell (Lindane) Lotion - scabicide 2. Calamine Lotion - antipruritic - protective
    29. 29. TYPES of LOTIONS NON MEDICATED LOTIONS1. Jergen’s Lotion - emollient 2. Aveeno Lotion - moisturizer
    30. 30. EMULSIONS: DEFINITION A dispersion in which the dispersed phase is composed of small globules of liquid distributed throughout another liquid, in which it is immiscible. A two-phase system in which one immiscible liquid is intimately dispersed in another liquid (as droplets).
    31. 31. PHASES OF EMULSIONSDISPERSED PHASE– the liquid droplet, internal phase, or discontinuous phase.DISPERSION MEDIUM– the liquid vehicle, external phase, or continuous phase
    32. 32. TYPES OF EMULSIONS W/O emulsion - water is the internal phase - oil is external phase O/W emulsion - oil is the internal phase - water is external phase
    33. 33. EMULSIFYING AGENTS Any compound that lowers the interfacial tension and forms a film at the interfaceTYPES:1. Natural emulsifying agents – acacia, tragacanth, agar, pectin, gelatin, methylcellulose2. Synthetic emulsifying agents – anionic, cationic, or nonionic
    34. 34. SYNTHETIC EMULSIFIERS ANIONIC AGENTS – include sulfuric acid esters, sulfonic acid derivatives, and soapsAlkali soaps – form O/W emulsionMetallic soaps – form W/O emulsionMonovalent and Polyvalent soaps – form W/O emulsion
    35. 35. SYNTHETIC EMULSIFIERS CATIONIC AGENTSUsed as surfactant in 1% concentrationExample: Benzalkonium chloride
    36. 36. SYNTHETIC EMULSIFIERS NONIONIC EMULSIFIERSResistant to the addition of acids and electrolytesExamples:Sorbitan esters – SPANS, hydrophobic, low HLB values, form W/O emulsionsPolysorbates – TWEENS, hydrophilic, high HLB values, form O/W emulsions
    37. 37. HLB SYSTEM HYDROPHILE – LIPOPHILE BALANCE Used to classify non-ionic surfactants All NON –IONIC surfactants have an HLB value. The higher the HLB number, the more hydrophilic The lower the HLB number, the more lipophilic
    38. 38. HLB SYSTEMHYDROPHILIC SURFACTANTS High HLB values (>10) Form O/W emulsionLIPOPHILIC SURFACTANTS Low HLB values (1-10) Form W/O emulsion
    39. 39. Application of SurfactantsHLB VALUE SURFACTANT RANGE APPLICATION 1–3 Antifoaming agents 4–6 Water-in-Oil emulsifiers 7–9 Wetting agents 8 – 18 Oil-in-Water emulsifiers 13 – 15 Detergents 10 – 18 Solubilizing agents
    40. 40. METHODS OF PREPARATION1. WET GUM METHOD (English method) 4:2:1 of oil : water : gum Formation of Primary Gum as the nucleus of the emulsion.
    41. 41. METHODS OF PREPARATION2. DRY GUM METHOD (Continental method) 4:2:1 ratio of oil: water: gum Formation of Primary Mucilage as the nucleus of the emulsion
    42. 42. METHODS OF PREPARATION3. BOTTLE METHOD – (Forbes Bottle method or 2:2:1 method) 2:2: 1 ratio of oil : water : gum Applicable to emulsions containing Volatile Oils.
    43. 43. METHODS OF PREPARATION4. NASCENT SOAP METHOD The soap is formed first by mixing equal volumes of oil and alkali The soap acts as emulsifying agent A 50:50 ratio of oil to water ensures sufficientemulsion
    44. 44. THEORIES OF EMULSIFICATION1. SURFACE-TENSION THEORY Initially, when oil and water are mixed it becomes immiscible due to the presence of surface tension. The use of surfactants result in the lowering of interfacial tension between two immiscible liquids.
    45. 45. THEORIES OF EMULSIFICATION2. ORIENTED WEDGE THEORY This theory assumes monomolecular layers of emulsifying agent curved around a droplet of the internal phase.
    46. 46. THEORIES OF EMULSIFICATION3. PLASTIC FILMOR INTERFACIAL FILM THEORY This theory places the emulsifying agent at the interface between the oil and water, surrounding the droplets of the internal phase as a thin layer of film adsorbed on the surface of the drops.
    47. 47. THEORIES OF EMULSIFICATION4. VISCOSITY THEORY The final product will exhibit increased viscosities. When the contents are agitated, it will have a thick, creamy consistency which will make the emulsion acceptable for use.
    48. 48. METHODS OF DETERMINING THE TYPE OF EMULSION DYE SOLUBILITY TEST Uses methylene blue or brilliant blueIf the dye is dissolve and uniformly diffuse – O/WIf the particle of the dye lie in clumps on the surface – W/O
    49. 49. METHODS OF DETERMINING THE TYPE OF EMULSION DILUTION TESTIf freely mixes with water – O/WIf not diluted with water – W/O
    50. 50. METHODS OF DETERMINING THE TYPE OF EMULSION ELECTRIC CONDUCTIVITY TEST O/W conducts electric current W/O do not conduct electric current
    51. 51. MICROEMULSION Thermodynamically stable system Optically transparent isotropic mixture of a biphasic O/W system stabilized with surfactants
    52. 52. MICROEMULSION Diameter of particle: 100 Å (10 mμ) to 1000 Å (Angstrom)
    53. 53. AEROSOLS Pressurized dosage forms designed to deliver drug systemically or topically with the aid of a liquefied or propelled gas (propellant). A dispersion of solid, liquid or gas forms of a drug in gas.
    54. 54. AEROSOLS:COMPONENTS Product concentrate PropellantCompressed gases – CO2, N2, NOLiquefiable gases – saturated HC’s, CFC’s, dimethyl ether, and HFC’s
    55. 55. AEROSOL CONTAINER
    56. 56. ADVANTAGES Convenience of application Stability Wide range of products to be dispensed as sprays, foams, or semisolidsDISADVANTAGES Environment hazard Inadvertent inhalation of the gas
    57. 57. FILLING METHODS of AEROSOLSI. Cold Filling Method Product concentrate and propellant are cooled at -34.5 to -40°C Dry ice and Acetone are the cooling systems used.
    58. 58. FILLING METHODS of AEROSOLSII. Pressure Filling Method 1.Product concentrate is quantitatively placed in the aerosol container. 2.Valve assembly inserted and crimped in place. 3. Liqiefied gas (under pressure) is metered into the valve system.
    59. 59. ACTUATOR MOUNTING CUP WITH FLOWED-IN GASKETSTEM HOUSINGSPRING DIP TUBEGASKET 59
    60. 60. PARTS of the VALVE ASSEMBLY ACTUATOR MOUNTING CUPSPRING GASKETHOUSING
    61. 61. Types of Aerosols1. Inhalational aerosols – MDI’s2. Topical aerosols Tolnaftate (antifungal)3. Vaginal aerosols Nonoxynol- 9 (contraceptive foam)4. Rectal aerosols Proctofoam
    62. 62. METERED DOSE INHALERS (MDI’s) These devices allow a drug to be inhaled as a fine mist of drug or drug-containing particles for systemic or pulmonary delivery Use special metering valves to regulate the amount of formulation and the drug that is dispensed in
    63. 63. METERED DOSE INHALERS (MDI’s) Commonly employed in asthma therapy

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