Solid dosage forms Flashcards
What is an oral dosage form?
Medicinal products in the solid form to be administered in the mouth and absorbed by the GI system or oral cavity
What are tablets?
A solid preparation manufactured by compressing uniform volumes of particles which contain a single dose of one of more active ingredients and excipients.
What are capsules?
solid preperations with either hard or soft shell gelatine capsules containing a single dose of API
What classifications of powders?
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
What are light techniques used to measure particle size
- 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
What sieving techniques are used to determine particle size?
- 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
What alternaive methods can be used to measure particle size?
- 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
What is particle size analysis the equivalvent sphere?
Make an equivalent sphere if particle not spherical to measure it. Equivalent sphere of length and volume of particle
What are the 2 types of methods of powder sampling?
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
What is adhesion and what is cohesion?
Adhesion: 2 chemically disimilar materials stick together
Cohesion: 2 chemically similar materials stick together
What are examples of cohesive and adhesive forces?
- 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
When will a powder flow?
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
What techniques are used to measue powder flow?
- Angle of repsonse
- bulk density
- critical orfice diameter
(See powders and granulation for more depth)
Why are all medicines mixtures?
- Due to small quantities of the drug
Or
- Poor processing characteristics of the drug
Or
- Special characteristics requirements of the medicine
What does mixing and segregation mean?
Blending
Demixing
What does Pecolation segregation mean?
Seperation of mixed particles according to size (smaller particles move down)
What does trajectory segregation mean?
- mass based seperation (heavier particles move further before stopping)
Elutriation segregation
density and size based segregation
What does trituation mean?
mixing in a motor with a peatle
What types of mixtures are there?
- 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
What is scale of scutiny in relation to powder mixing?
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
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?
(25 / 10) x 100 = 250 mg
(unit dose / conc. in blend) x 100 = SOS
What is particle size reduction?
Reducing larger solid masses into smaller units by mechanical means
Why is particle size reduction required?
- 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
What are problems associated with particle size reduction?
- Product degradation
- Product aggregation
- Polymorphic change
- Alternative moisture content ( hygroscopic/ deliquecent)
- Contamination
What are excipent functions?
- Bulk up API
- Assist in production
- Improve stability
- Assist Bioavailability
- improve patient complicance
- Aid identificatino
What is the purpose of a dilutent and examples?
Used to fill/ bulk out or aid processing
- Lactose: cheap, inert, safe
- Sugars: Mannose, Sucrose
- Celluloses: MCC, Calcium Phosphate
LMMSC
What does a Binder do? Examples?
Adhesives to bind powders together during granulation and compression
- MCC, PVP, Starch
What is the purpose of distinigrants? Examples?
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
What is the purpose of a glidant? Examples?
Improves powder flow and reduces intra-particular friction
- Silica, Talc
What is the purpose of lubricants? Examples?
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
What is the purpose of colouring?
AIds identification and alters appearance
What is the purpose of flavourings?
- Masks unplesant taste
- More palatable
- identification
- compliance
Purpose of solvents? examples?
Used in capsules to carry drugs. PEGS
Purpose of coating, adsorbents, sorbents
- Improve appearance, control time, location of drug release
- Improve uniformity of drug distribution
- Allows OSDFs to be formed from liquid drugs
