5925 Simberg Solid Dosage Forms - Powders

How to describe particle size for spherical particles

Diameter

How to describe particle size for irregular shaped particles

Dimensions + Diameter d of a sphere that occupies the same volume

Polydispersity index (PDI) for monodisperse particles is

-particle are all the same size

< 0.1 - narrow/ sharpe peaks

Polydispersity index (PDI) for polydisperse particles is

-particles are all different size

>1 - broad distribution

Pharmaceutical powders do NOT show ____

a normal distribution

Tyler mesh size

is the number of openings per (linear) inch of mesh

The larger the Tyler mesh number the

smaller the opening

Q: Which size cannot be measured with sieves?:

Nanoparticle & Bacteria

The combined surface area for the same mass of powder increases

2-fold

When diameter d is decreased 2 times, surface area of each particle decreases

4 times

Bulk properties of powders

Density, Porosity, Wettability & Flowability

True density

Density without consideration of voids (no inter- or intra-particle pores)

Bulk (apparent) density

Considers interparticle and intraparticle spaces that add to the volume

For a porous particle:

Density (true) ___ Density (bulk)

Density (true) >

Which material has higher bulk density, wheat grains or wheat flour?

Flour, particles are smaller (fluffier)

How reducing particle size in powders affects total surface area?

increases it

reducing particle size always increases

surface area

Porosity of powder

the fraction of void volume (air) in a powder material.

Wettablity

ability to interact with water and absorb water

how easily water gets into the pores (penetrates) of a powder is called

wettability

High surface tension = large contact angle = ___wettability

low

Low surface tension = small contact angle= ___ wettability

high

High surface tension = ____ contact angle = low wettability

large

Low surface tension = ____ contact angle = high wettability

small

____ is Determined by the liquid-liquid interactions vs. liquid-solid interactions

contact angle

Capillary movement in the pores depends on the

surface tension

concave meniscus - liquid interacts with the walls is a ___ surface tension

LOW

Convex meniscus - dropet does not want to spread out, this means the surface tension is

HIGH

If the droplet wants to stay together, it doesnt not want to _____, this is high surface tension.

spread

Wetting agents decrease ___ & ____; and increase wettability

surface tension, contact angle

In order to dissolve powder, first add ____ to powder (prewet) and then add solvent

wetting agent

Flowability:

cohesive properties of powder particles; how well the powder stays together.

Glycerol, ethanol, surfactant examples of

Wetting agents

Which liquid moves faster in pores?:

With low surface tension & The one to which we added ethanol

What should be done to particle size to improve flowability?

increase particle size; larger particle size has better flowability. less interaction with the particle, greater flowability.

Q. Regarding the angle of repose, which one is correct?

a)Powdered sugar has a larger AR than granulated sugar

b)No effect of size

c)Humidity will increase the AR of powders

d)A+C

Powdered sugar has a larger AR than granulated sugar & Humidity will increase the AR of powders

Blending

Performed to achieve a homogenous mixture of the components in a pharmaceutical powder; better when the particles are uniform in size.

Percentage Strength

Medication concentrations are often written as a number followed by a percent sign (e.g., 2%), which implies a specific weight or volume concentration of g/100 units.

2g of active substance in 100g powder is 2% percent strength

Ratio Strength:

part of drugs in 100 pars of liquid/solid,

where units are always gram or ml

2g of active substance in 100g powder is 2:100 or 1:50 ratio strength

•When fraction x of powder A is >10%, use ____ blending (add A to B and mix).

direct

When fraction x of powder A is less than 10%, use

geometrical dilution

To prepare Milk Thistle powder with

2:50 ratio strength in methylcellulose, which blending method would you use?

geometrical

How many grams of talc should be added to 1 lb of a powder containing 20 g of zinc undecylenate per 100 g to reduce the concentration of zinc undecylenate to 3% percent strength?

2661 g talc

A physician prescribes 1.6 million units of penicillin G potassium daily for 7 days. If 1 mg of penicillin G potassium is equal to 1595 penicillin G units, how many 250-mg tablets of penicillin G potassium should be dispensed for the prescribed dosage regimen?

28 tabs

Packing stats:

the weight or powder that can be packed into a capsule of a given size

Diluent

An (inert) substance added to increase the bulk weight of a powder in a capsule

It is challenging or impossible to accurately weigh a small amount of powder.

Cannot pack a capsule with a small amount of powder.

Class A prescription balance: 6mg error, 5% accuracy: 120 mg minimum weight.

Trituration

Continuous rubbing or grinding with a mortar and pestle. Useful for hard powders, tablets

Pulverization by intervention

Dissolve in "intervening" solvent (alcohol, acetone), Mix in mortar or spread on ointment slab & finally Solvent evaporates (solid recrystallizes or precipitates as finer powder)

Pulverization by intervention Useful for

-Hard, crystalline powders that do not easily triturate

-"gummy" substances

Trituration Useful for

hard powders, tablets

Levigation

Uses a small amount of solvent in which the particles are insoluble then triturate with mortar and pestle or spatula

Levigation Useful

technique when making ointments and suspensions

Capsules are

solid dosage forms in which a drug substance is enclosed in a hard or soft soluble container or shell

Advantages of Capsules

•Easily filled extemporaneously or commercially

•Tasteless

•Easily administered

•Dose can be individualized (not possible with tablets)

•Preferred in early stage clinical trials

Capsule composition

•Capsule itself

•Diluent (inert sibstance)

•Active pharmaceutical ingredient API

Gelatin capsules - made from

hydrolyzed collagen that can absorb water in high humidity conditions

Soft elastic capsules

Contain gelatin, plasticizer (sorbitol, glycerol), preservative; Thermally sealed, open up in the stomach within 5 min

What are the advantages of capsules over powders?

capsules easier to swallow and manufacture.

What particle has a larger surface area?

spherical or spherical porous (assuming the same volume)

spherical porous

What particle has a larger surface area?

cubical with each side "x" or spherical with diameter "x"

cubical

Can particles that show symmetrical (gaussian) size distribution be poly-dispersed at the same time?

Yes

Which measurement method is the most practical to determine particle size?

sieves

During trituration of powder, particle diameter decreases 10-fold. how many fold the surface are increase?

100

How does the addition of glycerol affect wettability of powders?

increases because glycerol decreases surface tension.

What needs to be done to improve wettability of a powder? How could this be done?

Improve wettabilty means improving the ability for water to get into pores, but adding a disruptor/ wetting agent, decreasing the surface tension, and decreasing the contact angle, angel of repose, increases wettablity.

Which liquid runs faster in pores, with low surface tension or high surface tension?

low surface tension

Why you cannot weigh 1 mg on a class A balance

to get 5% accuracy, the minimum weight needs to be 120 mg (6mg is 5%).