Solid dosage forms

Question 1

What is an oral dosage form?

Answer 1

Medicinal products in the solid form to be administered in the mouth and absorbed by the GI system or oral cavity

Question 2

What are tablets?

Answer 2

A solid preparation manufactured by compressing uniform volumes of particles which contain a single dose of one of more active ingredients and excipients.

Question 3

What are capsules?

Answer 3

solid preperations with either hard or soft shell gelatine capsules containing a single dose of API

Question 4

What classifications of powders?

Answer 4

size:

• >1000um = coarse
• >100<1000um = intermediate
• >5<100um = fine
• <5um = ultra fine

Shape:

• Spherical - good flow
• acicular - poor flow

Density:

More dense - heavier (better)

Less dense - lighter

Question 5

What are light techniques used to measure particle size

Answer 5

• Microscopy: easy, multiple samples needed, only useful for particles visiable to naked eye
• SEM ot TEM (scanning/ transmission electron microscopy): ultrafine range of particles. Can observe surface texture
• Laser light difraction
• Proton correlation spectroscopy

Question 6

What sieving techniques are used to determine particle size?

Answer 6

• Sieving: sample placed on top of stack of seives and aggitated. Smaller particles that sieve apeture pass through onto next mesh.
• Air jet sieving: Using pulses of air and vacuum to push and pull particles off and onto a screen. Particles which pas through are transferred onto a larger apeture screen and the process repeated.
• Inertial impacation: used for inhalation products

Question 7

What alternaive methods can be used to measure particle size?

Answer 7

• Time of flight measurement: TIme of passage between 2 laser beams
• Electrical stream sensing zone method: Monitors charge of electricsl signal which occurs as a particle passes through an orfice
• Sedimentation method: Using stokes law and reynolds number to determine particle size based on time take to settle in a fluid of known viscosity

Question 8

What is particle size analysis the equivalvent sphere?

Answer 8

Make an equivalent sphere if particle not spherical to measure it. Equivalent sphere of length and volume of particle

Question 9

What are the 2 types of methods of powder sampling?

Answer 9

Dynamic: take proportion of sample when in motion (better). Take several samples at varrying times

Static: Take sample when product at rest

Important to take whole sample at one time

Question 10

What is adhesion and what is cohesion?

Answer 10

Adhesion: 2 chemically disimilar materials stick together

Cohesion: 2 chemically similar materials stick together

Question 11

What are examples of cohesive and adhesive forces?

Answer 11

• Van der Waals: decrease as particle size increases
• mechanical forces: When particles become interlocked due to shape and roughness
• Frictional forces: electrical forces caused by friction between particles
• Capillary forces: from adsorbed liquid on the surface of a particle

Question 12

When will a powder flow?

Answer 12

When an external force is applied by will resist stressed below a limiting value.

Depends upon forces resisting flow e.g. adhesion/ cohesion and forces promoting flow e.g. gravity and applied stress

Question 13

What techniques are used to measue powder flow?

Answer 13

• Angle of repsonse
• bulk density
• critical orfice diameter

(See powders and granulation for more depth)

Question 14

Why are all medicines mixtures?

Answer 14

• Due to small quantities of the drug

Or

• Poor processing characteristics of the drug

Or

• Special characteristics requirements of the medicine

Question 15

What does mixing and segregation mean?

Answer 15

Blending

Demixing

Question 16

What does Pecolation segregation mean?

Answer 16

Seperation of mixed particles according to size (smaller particles move down)

Question 17

What does trajectory segregation mean?

Answer 17

• mass based seperation (heavier particles move further before stopping)

Question 18

Elutriation segregation

Answer 18

density and size based segregation

Question 19

What does trituation mean?

Answer 19

mixing in a motor with a peatle

Question 20

What types of mixtures are there?

Answer 20

• Positive mixtures: diffusion, irreversible (no problems)
• Negative: Density, shape, size differences. Spontaneously seggregates
• Neutral: no movement without addition of energy
• Types that can change: Not neg to pos. Neg to Neu possible

Question 21

What is scale of scutiny in relation to powder mixing?

Answer 21

What sample size is required to determine if the formulation has been mixed enough/ has correct dose of drug

e.g. if need 300mg of drug take 300mg sample

equal to weight/ volume of dosage unit

Question 22

calculate scale of scruntiny:

Blend contains 10% API, 25 % Excipient X and 65% Excipient Y. Each dose needs to contain
25 mg. What is the scale of scrutiny?

Answer 22

(25 / 10) x 100 = 250 mg

(unit dose / conc. in blend) x 100 = SOS

Question 23

What is particle size reduction?

Answer 23

Reducing larger solid masses into smaller units by mechanical means

Question 24

Why is particle size reduction required?

Answer 24

• Optimise dissolution rate
• Improve aesthetics and stability
• improved production efficiency
• breakdown of cells to allow extraction of APIs from plants
• Provide appropriate size for drug targeting (respiratory med)

Energy needs to be put in to initate crack propagation

Question 25

What are problems associated with particle size reduction?

Answer 25

* Product degradation * Product aggregation * Polymorphic change * Alternative moisture content ( hygroscopic/ deliquecent) * Contamination

Question 26

What are excipent functions?

Answer 26

* Bulk up API * Assist in production * Improve stability * Assist Bioavailability * improve patient complicance * Aid identificatino

Question 27

What is the purpose of a dilutent and examples?

Answer 27

Used to fill/ bulk out or aid processing * **Lactose**: cheap, inert, safe * Sugars: **Mannose, Sucrose** * Celluloses: **MCC, Calcium Phosphate** LMMSC

Question 28

What does a Binder do? Examples?

Answer 28

Adhesives to bind powders together during granulation and compression * **MCC, PVP, Starch**

Question 29

What is the purpose of distinigrants? Examples?

Answer 29

Breaks up solid unit dosage form following ingestion * **MCC, PVP, Starch, (Bi)Carbonate** Three mechanisms: * Facilitation of water uptake * Rupture of tablet by swelling * Rupture of tablet by CO2 production

Question 30

What is the purpose of a glidant? Examples?

Answer 30

Improves powder flow and reduces intra-particular friction * Silica, Talc

Question 31

What is the purpose of lubricants? Examples?

Answer 31

Used in tablet/ capsule filling. Ensures formation and smooth ejection of tablets. - reduces friction and prevents adherance * **Magnesium sterate, sodium lauryl sulphate** 2 methods: Fluid, boundary

Question 32

What is the purpose of colouring?

Answer 32

AIds identification and alters appearance

Question 33

What is the purpose of flavourings?

Answer 33

* Masks unplesant taste * More palatable * identification * compliance

Question 34

Purpose of solvents? examples?

Answer 34

Used in capsules to carry drugs. PEGS

Question 35

Purpose of coating, adsorbents, sorbents

Answer 35

* Improve appearance, control time, location of drug release * Improve uniformity of drug distribution * Allows OSDFs to be formed from liquid drugs