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
SUSPENSIONS: DEFINITION Disperse systems containing finely divided, insoluble drug particles (“suspensoids’) distributed somewhat uniformly throughout a liquid vehicle.
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)
REASONS for SUSPENSIONS1. For improving product stability2. Ease of administration and flexibility in administration of a range of doses3. For masking unpleasant taste of
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
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
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
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)
SUSPENDING AGENTS: TYPES AND EXAMPLES2. CLAYS Silicates that are anionic in aqueous dispersion Strongly hydrated Exhibit thixotropyBentonite (as 5% magma), Veegum
SUSPENDING AGENTS: TYPES AND EXAMPLES3. OTHER AGENTS Agar Chondrus(carrageenan) Gelatin Pectin Gelatinized Starch
TYPES OF SUSPENSION1. ORAL SUSPENSIONS Ready to use Dry powders for reconstitution Uses: Antacid,Anthelmintic, Antibacterial(see table 14.1 pp.390-391)
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.
TYPES OF SUSPENSION3. OPHTHALMIC SUSPENSIONS Particle size must not exceed 10 microns
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.
TYPES OF SUSPENSION3. OPTHALMIC SUSPENSIONS Particle size must not exceed 10 microns Particles must be “impalpable”
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.
TYPES OF SUSPENSION 5. RECTAL SUSPENSIONS Barium Sulfate for Suspension, USP May be employed orally or rectally for diagnostic visualization of the GIT.
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.
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
CLASSES OF SUSPENSION1. LOTIONS2. GELS3. MAGMAS AND MILKS4. MIXTURES
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.
LOTIONS Prepared by: (1) Trituration method (2) By chemical reaction method
TYPES of LOTIONS NON MEDICATED LOTIONS1. Jergen’s Lotion - emollient 2. Aveeno Lotion - moisturizer
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).
PHASES OF EMULSIONSDISPERSED PHASE– the liquid droplet, internal phase, or discontinuous phase.DISPERSION MEDIUM– the liquid vehicle, external phase, or continuous phase
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
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
SYNTHETIC EMULSIFIERS ANIONIC AGENTS – include sulfuric acid esters, sulfonic acid derivatives, and soapsAlkali soaps – form O/W emulsionMetallic soaps – form W/O emulsionMonovalent and Polyvalent soaps – form W/O emulsion
SYNTHETIC EMULSIFIERS CATIONIC AGENTSUsed as surfactant in 1% concentrationExample: Benzalkonium chloride
SYNTHETIC EMULSIFIERS NONIONIC EMULSIFIERSResistant to the addition of acids and electrolytesExamples:Sorbitan esters – SPANS, hydrophobic, low HLB values, form W/O emulsionsPolysorbates – TWEENS, hydrophilic, high HLB values, form O/W emulsions
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
HLB SYSTEMHYDROPHILIC SURFACTANTS High HLB values (>10) Form O/W emulsionLIPOPHILIC SURFACTANTS Low HLB values (1-10) Form W/O emulsion
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.
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
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.
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
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.
THEORIES OF EMULSIFICATION2. ORIENTED WEDGE THEORY This theory assumes monomolecular layers of emulsifying agent curved around a droplet of the internal phase.
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.
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.
METHODS OF DETERMINING THE TYPE OF EMULSION DYE SOLUBILITY TEST Uses methylene blue or brilliant blueIf the dye is dissolve and uniformly diffuse – O/WIf the particle of the dye lie in clumps on the surface – W/O
METHODS OF DETERMINING THE TYPE OF EMULSION DILUTION TESTIf freely mixes with water – O/WIf not diluted with water – W/O
METHODS OF DETERMINING THE TYPE OF EMULSION ELECTRIC CONDUCTIVITY TEST O/W conducts electric current W/O do not conduct electric current
MICROEMULSION Thermodynamically stable system Optically transparent isotropic mixture of a biphasic O/W system stabilized with surfactants
MICROEMULSION Diameter of particle: 100 Å (10 mμ) to 1000 Å (Angstrom)
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.
ADVANTAGES Convenience of application Stability Wide range of products to be dispensed as sprays, foams, or semisolidsDISADVANTAGES Environment hazard Inadvertent inhalation of the gas
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.
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.
ACTUATOR MOUNTING CUP WITH FLOWED-IN GASKETSTEM HOUSINGSPRING DIP TUBEGASKET 59
PARTS of the VALVE ASSEMBLY ACTUATOR MOUNTING CUPSPRING GASKETHOUSING
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
METERED DOSE INHALERS (MDI’s) Commonly employed in asthma therapy