Micromeritics PDF

Physical Pharmacy Micromeritics Khalid T Maaroof PhD.Pharmaceutical sciences 2023 1  Micromeritics The science and technology of small particles size, and hence surface area, of a particle can be related...

Physical Pharmacy Micromeritics Khalid T Maaroof PhD.Pharmaceutical sciences 2023 1  Micromeritics The science and technology of small particles size, and hence surface area, of a particle can be related in a significant way to the physical, chemical, and pharmacologic properties of drugs. 2  ParticleInsize Pharmaceutics: & pharmaceutics Physical stability: The particle size in a formulation influences the physical stability of the suspensions & emulsions. Smaller the size of the particle, better the physical stability of the dosage form. Dose uniformity: Good flow properties of granules & powders are important in the manufacturing of tablets & capsules. Release & dissolution: Particle size & surface area influence the release of a drug from a dosage form. Higher surface area allows intimate contact of the drug with the dissolution fluids in vivo & increases the drug solubility & dissolution. Absorption & drug action: Particle size & surface area influence the drug absorption & subsequently the therapeutic action. Higher the dissolution, faster the absorption & hence quicker & greater the drug action. 3  Particle size is usually expressed or quantified as diameter or volume But diameter is mostly used because sometimes volume measurement is difficult. How to measure the size of this particle? 4  But for irregular particles: The Surface diameter, ds, is the diameter of a sphere having the same surface area as the particle. The Volume diameter, dv, is the diameter of a sphere having the same volume as the particle. The Projected diameter, dp, is the projected diameter of a sphere having the same observed area as the particle. The Stokes diameter, dst, is the diameter which describes an equivalent sphere undergoing sedimentation at the same rate as the asymmetric particle. 5  Particle size distribution It very rarely occurs that all particles in a sample are of the same size (monodisperse). There is usually a mix of different sizes present (polydisperse). Number of particles Number of particles Size Size monodisperse polydisperse 6  Particle Size Distribution Frequency distribution curve. Normal distribution curve 7  Methods of particles size measurement Microscopy Sieving Sedimentation technique Other techniques: 8  Optical microscopy Range : 0.2 - 100µm 300-500 particles should be measured in this case for good representation. only two dimensions are visible. Advantages and disadvantages? 9 Example of microscopy data σ n d 36850 dav = = = 103.8 σn 355 10  Sieve method  Sieve analysis is performed using a nest or stack of sieves where each lower sieve has a smaller aperture size than that of the sieve above it.  Sieving method used to find weight size distribution and average diameter  Error causing variables include:  sieve loading duration  intensity of agitation.  sieving can cause attrition of granular materials 11  Example of sieving data σ(% retained ) × ( ave size ) 29.232 dav = = = 0.2923mm 100 100 12 Number & weight distribution curves 13  Sedimentation method (range: 0.08-300 µm) By measuring the terminal settling velocity of particles through a liquid medium in a gravitational or centrifugal environment. Stocks law is used to measure the size. 18 0 h d st = (p − s )gt v : velocity of settling h : distance of fall in time t p : density of particle s : density of dispersion medium g : acceleration due to gravity 0 : viscosity of medium 14 Why gravitational sedimentation method is not applicable to colloidal formulations??  Other methods In a machine like coulter counter the powder is suspended in an electrolyte solution. This suspension is then made to flow through a short insulated capillary section between two electrodes and the resistance of the system is measured. When a particle passes through the capillary there is a momentary peak in the resistance, the amplitude of the peak is proportional to the particle size (volume). Counting is done by a computer. Precise But expensive 15  Powder properties Measuring Porosity of powders: Void volume (v) : the volume of space among particles Vb − Vp Vp 𝑣 = Vb − Vp 𝜀= = 1− Vb Vb Bulk volume (Vb) True volume (Vp) 16  Densities of Particles True density (): Density of the actual solid material True density Granule density ( g) (Particle density): The mass of particles divided by the volume (including intra-particle pore volumes) Tap density Granule density Bulk density ( b) (Apparent density): ? The mass of a powder divided by the bulk volume Bulk density 17  Particle size distribution: Cumulative curves Cumulative curves are another way to express particle size distributions. Lets say we have this size data: Size range 40-45 45-50 50-55 55-60 Number Frequency 7 12 15 3 Cumulative Frequency 7 19 34 37 (undersize) Upper class boundary 45 50 55 60 18  Cumulative frequency curve 40 Cumulative frequency 30 20 10 0 35 40 45 50 55 60 Size (mm) 19  Types of cumulative curves Cumulative frequency curve: particle number versus size. Cumulative percentage curve: percentage vs size. Cumulative weight curve: weight vs size. Cumulative undersize VS Cumulative oversize 20  Median 40 Cumulative frequency 30 20 10 0 35 40 45 50 55 60 Height (mm) Median ≈ 49mm 21