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Powders & Granules - Coggle Diagram

- - - - Coarse division:
        
        involves cutting, chopping, crushing, grinding, milling, micronizing, and/or trituration.
        
        depends on the type of equipment used,
        
        depends on the raw material to be treated (vegetable, synthetic, mineral)
        
        depends on the particle size
      - Comminution: like coarse division but more intense. Appropriate devices are used to produce particles smaller than that of coarse division. Factors affecting device choice:
        
        Physical properties of the drug (hardness, abrasiveness, elasticity, friability, fribrousness, moisture content)
        
        Initial feed particle size and degree of size reduction desired
        
        Particle shape desired
        
        Quantity of material to be treated
    - - Particle size of powders influence dissolution
        rate in vivo, which influences absorption rate and the onset of therapeutic activity. Therefore this is the MOST IMPORTANT FACTOR in mixing powders.
      - Volumetric filling: used by manufacturing
        equipment which controls the mass of drug and other ingredients
        
        Alterations of the amount of the drug incorporated can reduce the content uniformity.
        
        Particle size affects flow and packing properties, which affects volume of powders during each step of manufacturing.
        
        Goal: particle size to be as uniform as possible
      - Ideally, do not use spherical equivalent diameter to determine particle size of powder. Instead, measure:
        
        equivalent volume
        
        sedimentation volume
        
        mass
        
        sieve mass of particle
        This is due to particle size distribution, which can be plotted on a histogram (%frequency of particle size against particle size diameter)
    - - Mixing and segregation
        are important parameters in mixing and segregation, especially during storage.
        
        Different flow characteristics to be considered during process of manufacturing and packaging (required for essential quality control and optimization formulation)
      - Excipients added have the following functions:
        
        Filler/diluent: dilute the active powder drug to give volume
        
        Glidant: improve the packaging properties
        
        Sweeteners/Flavouring: tastes masking and improve patient compliance
  - - - Particle size: ensure powders are milled and sieved before mixing so that they are the same size
      - Density of components: affects the stability of powder mixtures. Heavier particles have fall to the bottom, the lighter particles rise to the top of the powder bed.
      - Proportion of each component: Homogenity is affected. Components should be perfectly distributed throughout the whole mixture. If one component is too small, good homogeneity is more difficult to obtain as compared to if all components are of equal amounts.
      - If particle size, density and proportion are not under control, segregation/demixing can occur.
    - - Done by verifying the homogeneity of mixed powders, and determining the difference in amount of each component in each sample. (e.g. 3 diff samples from 3 diff locations in the same mixture)
      - Other characteristics of the mixed powder such as particle size, flavour, flow rate, and bulk density before and after tapping have to be verified
- - - - Drug then forms a solution close to pH 7, allowing rapid passage through the pylorus. This enables the drug to be rapidly and better absorbed as compared to conventional dosage forms
      - Requires very low and controlled relative humidity (<20%) to manufacture effervescent powders,
      - Powders that contain acid substances and carbonates/bicarbonates, which upon contact with water, react by releasing carbon dioxide.
    - - Acids: citric (monohydrate or anhydrate), tartaric, ascorbic (drug or excipient), fumaric, nicotinic, acetylsalicylic (drug or excipient), malic acids
        
        Anhydrides: glutaric, citric
        
        Acidic Salts: sodium dihydrogeno-citrate, sodium acid phosphate, sodium fumarate
      - Sources of CO2 Salts: Na2CO3, sodium carbonate, K2CO3, CaCO3, sodium glycine carbonate
      - Lubricants: PEG 6000 alone or in combination with sodium stearyl fumarate, sodium benzoate, sodium chloride, sodium acetate, or D,L-leucine
      - Binders: PVP, hydrogenated maltodextrin, maltodextrins, PEG 6000
      - Others: sweeteners, flavours, colours, surfactants, antifoaming agents