what aspects of solid dosage forms does the quality of mixing influence
efficacy, properties (right site, right rate), appearance, cost
definition of powder mixing
unit operatin aiming to treat two or more components so that each particle lies as nearly as possible in contact with a particle of each of the other components
what is a perfect mix?
a mix of two or more components where each particle lies as nearly as possible in contact with a particle of each of the other components
when is getting close to an ideal mix important?
small amount of potent drug
when is getting close to an ideal mix not important?
mixing in lubricants
what is a positive mix?
materials which mix spontaneously and irreversibly by diffusion e.g. gas/ miscible liquids. No energy required IF time is unlimited
what is a negative mix?
components tend to seperate unless energy is continuously input e.g. suspensions like calamine lotion. Or they tend to separate very slowly e.g. creams. Harder to form/ maintain and require higher mixing efficiency
what is a neutral mix?
static in behaviour, no tendency to mix/de mix e.g. ointments
what is a random mix?
a mix where the PROBABILITY of selecting a particular type of particle is the same at all positions, and is equal to the proportions of such particles in the mix
what is the scale of scrutiny?
to determine whether a random mix has been achieved and each dosage unit contains the right amounts an amount equal to the dosage unit is sampled.
what determines the number of particles in the scale of scrutiny?
sample weight, particle size, particle density
the greater the no. of particles and the greater the % of active the greater chance f obtaining the correct dose. Therefore what mixes are harder to mix?
components with large drug particles, very low dose drugs
how does selecting particular size fractions affect segregation?
removes dust/fines and lumps
how does milling of components affect segregation?
if all <30µm do not generally segregate
how does controlling crystallisation affect segregation?
gives particular shape/size
how does selecting excipients of similar density to active affect segregation?
how does granulation affect segregation?
so large numbers of particles are evenly distributed in each granule. however unless granules monosized smaller ones can fall to the bottom of the hopper, these will have a larger bulk density (less void) causing weight variation
how does reducing vibration/transport affect segregation?
how does powder hopper design affect segregation?
use hoppers designed so sloping surfaces do not form and powder resistance time is minimised
how does using multiple operations affect segregation?
use equiptment where several operations can be carried out without transferring the mix e.g. fluid bed drier, high speed mixer/granulator
how does the production of an ordered mix affect segregation?
if one powder is sufficiently small it may be come adsorbed onto the 'active sites' of a larger 'carrier' therefore segregation of fines can be minimised
ordered mixing is important in what kind of formulations?
direct compression, potent drugs, dry powder inhalation
how may segregation still occur in ordered mixes?
carrier particle diff sizes (if diff. sized carriers separate causing ordered unit segregation), another component competes for sites on the carrier and displaces adsorbed material (displacement segregation, this may occur when magnesium stearate is added), insufficient carrier particles (saturation segregation)