Powders&Sachets Flashcards
What is a powder ?
A pool of solid particles or same/ different chemical composition.
complex + heterogeneous
In what ways do powders act similar to: 1) liquids, 2) solids and 3) gases?
- FLOW like LIQUIDS
2) RESIST DEFORMATION (to a point) like SOLIDS
3) can be COMPRESSED like GASES
How can particle size be
a) estimated
b) determined?
a) equivalent sphere concept
1. Simplify size analysis for powders
2. Allow comparisons based on a single value
b) sieving- air jet sieve, sieving diameter (ds) corresponds to minimum apertrue size
what do Microscopy-based methods allow the determination of?
- Projected diameters =
independant of particle orientation (dp, da)
OR
dependant on particle orientation (dM. dF)
see video images
What is particle size distribution related to & whats it based on?
Relates to heterogeneity of a powder = impact on behaviour (dissolution rate, mixing, demixing, flow…)
- number distribution
- weight distribution
(* length, surface, volume distributions)
Particle size distribution: frequency curves-
Name for when particles all in same size class?
Narrow size distribution
Relation between particle sizes and size distribution?
higher variety of particle sizes detected in the powder = likely wider size distribution
obtained by generating a frequency histogram or curve.
how may size distribution be normalised for some powders?
by plotting the diameter values on a log scale
what do frequency curves + histograms allow the determination of?
whats the exception?
allow the mode, rather than the mean, to be determined, unless (of course) sizes are normally distributed
How to caluclate % frequency for particle size distribution table?
n (num of particles/freq) / total freq (add up whole column) x 100
normal distribution unlikely for powders but whats special about it?
mean, mode, median have same value
what is a skewed size distibution and what can be determined?
+ positively skewed: left peak = smaller mode, mean HIGHER than mode.
larger particles
- negatively skewed: right peak = higher mode value, mean LOWER than mode.
smaller particles
can only determine MODE directly
what does multimodal distribution imapct on?
2 modes- 2 peaks, use highest mode
impl on:
behaviour, properties of powder and final dosage form
what does cumulative frequence allow?
what does curve shape depend on
sigmoidal shape, MEDIAN rather than mean, to be determined.
shape changes depending on narrow/wideness of size distribution
what does sieving analysis allow?
a frequency can be determined for the undersize or oversize fractions
view table in noted about calculating frequency and %s.
how to obtain
a) number size distibution
b) weight distribution
a) microscopy based methods
b) sieving methods
T/F: BP clasisfication of powder fineness is based on mean particle size?
FALSE
A 250 micrometer sieve is placed on top of a receiver pan. The fraction retained on the sieve corresponds to the XXX fraction; the fraction of powder recovered in the receiver pan corresponds to the YYY fraction.
Retained XXX = oversize
Recovered YYY = undersize
For powders, flowability will depend on the balance between what two types of forces?
Flow promoting: drive flow
- gravity
- particle mass (related to density)
- angle of inclination
- applied mechanical force
and drag forces: resist flow x adhesion (diff) x cohesion (like) x electrostatic interactions x surface forces
Name the 2 drag forces that vary with particle size and moisture content
adhesion and cohesion
in what condition will a powder flow on?
when (flow promoting forces) > (drag forces)
what powder properties affect powder flow and whats the IDEAL for each?
particle shape: spherical
particle size: big (free flowing, more gravity, less adhesion+cohesion)
packing and porosity:
density: higher density
(moisture content: Low but not too dry)
ONLY IF ALL ELSE EQUAL
what does packing influence and what are the loosest and tightest forms?
how solid partcicles arranged in powder bed, will influence volume of powder bed.
Cubic: loosest, most porous
Rhombohedral: tightets, least porous
whats porosity and what is it for aggregates, real powder and polydisperse:
Porosity (e)= measure of how loosely/ tightly particles are packed.
For particles arranged in a cubic geometry: 48% of the powder volume is void.
Rhombohedral: 26%.
highest porosity: aggregates
then real powder
then polydisperse
impact of tapping on powder flow
tighten packing as INCREASE drag forces and DECREASE flow
whats bulk density?
related from packing thus porosity.
pB = m/v bulk density (g/cm3) = mass(g) / V (bulk volume (cm3)
in powders, bulk volume = sum of true volumes (vol of single powder particle + sum of void volumes (include both interparticular and intraparticular pores)
determined using a measuring cylinder.
how would you solve issues with powder flow? 4
- particle size and size distribution:
- remove smalls through sieving/adsorption
- granulate powder
- change shape
- spray-drying = regular shapes
- dry powder
- decrease cohesion. not too dry
- increase flow-promoting forces
- add excipeint: glidants, lubricant, anti-adherants
- mechanical assistance
when is angle of repose (AOR) determined?
and equation?
after powder left to flow and cone formed on flat surface.
Tan (alpha) = h (height poder cone) / r (radius of base of cone)
flatter cone = smaller AOR (25-30) = better flow :)
how is powder flow assessed using bulk density?
pB (poured density) = mass of powder / V0 (poured volume- bulk vol of known amount)
pT (tapped density) = mass of powder / VF(tapped volume)
how are Hausner ratio and Carrs index determined?
what are they indicatord of?
HR = pT (tapped vol) / pB (poured vol)
CI = (pT - pB)pT x 100
indicators of flowability.
want both values LOW: 1-10 CI/ 1-1.11 HR
examples of powders as dosage forms
- Powders for reconstitution: antibiotics, parenterals, sachets
- insufflation powders
- powders for inhalation
- granules
dispensed in bulk (multi-dose container) or as single dose unit (e.g. sachets).
use and packaging of bulk oral powders
contain non-potent active ingredients- minor ailments
dispense w measure( 5ml spoon) bottle with wide opening
bulk oral powders as dosage forms ads?
- increased stability and shelf life vs liquid
- large dose administartion possible
- fast absorption (esp if dissolved/dispersed in water)
Topical powders ads? (3)
ads:
- ease of use
- absorption of skin moisture
- reduce friction (chafing)
Where are insufflation powders administered and why rarely used?
admin in body cavities: nose, ear, vagina, tooth socket, throat
poor patient adherance, not convenient
powders for recon: role of and some examples of excipients
excipients: aid dissolution or prevent caking.
Others: preservatives, stabilisers, sweeteners, flavouring agents.
a problem/caution with powders for recon
product = suspension, drug conc in final product will vary with volume of vehicle/solvent added.
so must measure vol of solvent correctly to avoid over- or under-dosing.
Parenteral powders for reconstitution packaging
suitable vial to be reconstituted immediately before use. Small amounts of excipients may be added to the formulation, but most of the powder should be made of the drug.
what are eutectic mixtures and how handled?
result from combination of 2 powders. starts as solid then liquifies during processing at room temp
- force eutectic mixture: trigger liquification by mixing and processing powders
- prevent eutectic mix: mixx each separately with inert powder alr in formulation
quality assessment for powders for recon
before recon: powder
after recon: solution/suspension
Compounding of pharmaceutical powders main steps in production?
Size reduction:
- Breaks-up aggregates formed during storage
- Crush crystalline drugs/excipients into a finer powder
mixing:
- direct- for powders of similar properties
- doubling up method (geometric dilution)- START WITH SMALLEST VOLUME
calculate bulk volume by mass/density
what does pharmaceutical compounding method depend on?
the quantities required for the different powders and on their bulk volumes.
For powders with different bulk densities, mixing should be performed in increasing order of bulk volumes.
when may forcing eutectic mix be beneficial?
forcing the eutectic mixture can be beneficial as the liquefied mixture can be used to dissolve crystalline ingredients in the formulation.
If you are hoping to prevent the eutectic mixture, use a spatula and glass tile, rather than a mortar and pestle for mixing.
Why shouldn’t efflorescent powders be keep in low humidity environment?
they contain hydration/ crystallisation water- moisture will be released into environment in low humidity.
what type of powders (special cases) require additional measures for maintenance of inetgrity?
hygroscopic: absorb moisture form env,
deliquescent: liquify after moisture absorption)
efflorescent: release moisture into env.
what are the additional measures for special cases of powders
hygroscopic and deliquescent:
- The use of a desiccant
- The use of an excipient that can preferentially absorb humidity
efflorescent powders
-use anhydrous form, where appropriate and does not impact the properties of the final formulation.
how are effervescent powders formulated?
1) acid source: often citric + tartaric
2) CO2 source: sodium bicarb/ calcium carbonate
what reeaction do effervescent powders undergo and how stored?
when dispersed inw ater: neutralisation between acidic and basic parts. base = Carbonate, CO2 formed and released.
store away from moisture as interaction triggered neutralisation
what patients may need to use effervescent powders with care?
those on sodium restricted diet as when made using sodium bicarb, the powders have added source of Na
Use the Noyes-Whitney equation to explain how size influences drug release from powders
(SOM1): size linked to surface area.
smaller particles = dissolve faster
Discuss the advantages and disadvantages of sachets as solid dosage form
Discuss the formulation parameters relevant to sachet formulation
Suggest suitable excipients for sachet formulation
define sachet and what can be put inside?
small bags used to deliver small quantity of medicine.
dry solids (powders, granules)/ liquids
What are the advantages of sachets for patients?
- Easy to carry, convenient
- Available as a unit dose, unliekly to measure
- Easy to prepare: instructions
- Easy to swallow vs tablets/capsules
- If the empty sachet is available, we can identify what a patient has taken.
What are the advantages of sachets for pharmaceutical companies?
- Easy to manufacture-likely similar mixture as tabs,caps
- Easy to vary dose by adjusting filled volume
- Cost benefits-to ship
- Increased shelf-life like like other solid dosage forms
for what type of ingredients might the paper wrapping of sachets be unsatisfactory?
hygroscopic, volatile, or deliquescent inngredients
Who and when may dosing accuracy of sachets affect?
- not an issue with adults: whole sachet used
- paediatric sachets e.g. Movicol may only require a part of sachet (half..), making it difficult to measure the volume of water
- important to counsel patient on correct dosing esp in narrow therapeutic indexes
How do sachets help in terms of excipients?
they reduce the load especially in comparison of liquid dosage forms
e.g. in Amoxicillin preps, what formulations have most and least excipients?
highest for the powder for reconstitution (sugar free suspension)
lowest for the capsules.
Common excipients used in the formulation of powder sachets
Filler Dextrose, mannitol, maltodextrin, dibasic calcium phosphate
Glidant Silicon dioxide, colloidal silicon dioxide
Sweetener Mannitol, sorbitol, malitol, xylitol
Binder (e.g. granules) Starch, gum arabic, sorbitol
Encapsulation Cyclodextrins
Flavour
Why do capsules contain the fewest excipients?
less concern needed w organoleptic properties such as taste
What is required to achieve controlled-release in sachet formulations?
- granules
- these can be coated with gastro-resistant/modified-release coating e.g. Nexium
similar to capsules
what other (4) flowability criteria parameters must uniform filling of sachets meet? in addition to homogenous powder mix?
flow parameters: passble (Carrs index <25%)
particle settling time: fast - 1s allows for 60 sachets to be made a minute
wall friction angle: <20degrees
Kawakita 1/b parameter: >5 MPas
What influences powder settling time?
and whats the desired values?
- particle size
- size distribution
- true density
large and dense: settle faster
What is the Kawakita 1/b parameter and use?
- measures how much bulk volume changes under applied force
- used to assess powder flow
What is the Wall-Friction angle?
friction angle between the bulk powder and a solid surface e.g. the wall of a hopper/silo/bin
What does measuring the Wall Friction Angle tell us?
- how well designed the hopper/bin is as well as checking that the powder has a mass flow as opposed to a funnel flow
- the minimum inclination to make a powder flow i.e. a powder will only flow once resting elevated at a certain angle
desired wall friction angle for fast sachet production?
<20 degrees
How does a powder with funnel flow behave?
- may experience size-dependent particle demixing due to large and small particles having different flowabilities
- affects homogenity of powder
How does a powder with mass flow behave?
- Bulk powder moves as one
- Decreases risk of particles getting separated depending on size
A simple way to think of the wall friction angle
imagine this as the minimum inclination required to make a powder flow.
powder only flows when surface elevated at certain angle
2 crucial points in filling of pharmaceutical sachets in industry
suitable flow and settling times
as 1 sachet filled
how is shelf life of sachets maximised?
Sachets will generally be packaged using laminates
and coded to make it easier to track and branded (branding may vary per location).
What properties must sachet packaging possess?
- High mechanical performance: transport, storage
- Easily sealable: no powder loss
- Paper or plastic based
- Good chemical resistance
- Good moisture resistance
- Easy to use w/ easy instructions
- Child-resistant and safe
what property/factor important for sachet filling by volume
density- for right dose
also no clouds= dose uniformity
What would be the risk of having a wide size distribution?
Particle with different sizes will have different flow properties, therefore affecting the uniformity of filling
Why can preservative be excluded from sachet formulations?
Sachets are single dose units and are used shortly after opening.
why cant bulk powders be used for potent drugs?
accuracy of measurements- differ
ADR and efficacy impacted
what to consider when adjusting amount of water to add when reconstituting antibiotic?
susepension
dilute solution- vol unlikely to change as lot of liquid
more powder = will not dissolve. higher volume and conc of suspension
what to remember when filling suspension bottle
dont fill to top, need to shake! = uniforn dosage
drug absorbed faster in sachet or tablet?
sachet as requires no disintegration as tablet prior to absorption
= lot of diff forms for same drug
main advantages of dispensing an oral rehydration solution as a sachet
- Some advantages general to all sachets (increased shelf-life BUT DECREASED ONCE RECONS.,
easier to carry around)
Unit dose no measuring Easy prep Easy to swallow for kids Variable dose rel easy - Others more specific to the formulation of rehydration products (e.g. less waste vs. pre-formed solution)
Bulk oral powders as dosage forms disadvantages? (4)
x bulky packaging
x organoleptic properties
x only non-potent drugs
x still drug degradation-storage and packaging
A problem with topical powders and how to maintain/avoid?
Packaging used?
Avoid grittiness: control particle size well.
package: bottles with sifter tops = need good flow
Topical powders disads? (5)
disads/risks: x risk of blocking pores x irritation x contamination x inhalation risk x must be sterile if to be used on broken skin
How are powders for recon administered? And why used?
oral/parenteral.
increased shelf life (better than liquid)in large bottle
