Solid Dosage Forms & Micromeritics Flashcards
1
Q
Granule
A
agglomerates of powders
2
Q
Advantages of powder and granule dosage forms (3)
A
- more stable (ex- reconstituted antibiotics)
- faster dissolution rate
- convenient for large dose drugs (ex- Benefiber)
3
Q
Disadvantages of powder and granule dosage forms (4)
A
- bulky
- poor for low dose drugs: accuracy is difficult (ex- digoxin)
- not suitable for drugs inactivated in the stomach
- pronounced unpleasant taste (mask with effervescence)
4
Q
powder and granule dosage forms are dispensed as:
6
A
- bulk for internal use (ex- Metamucil, Slim-Fast)
- divided for internal use (ex- Tums powder packs, Theraflu)
- reconstitution (ex- Amoxil, Solu-Medrol)
- dusting powders for external use (ex- baby powder, Tinactin)
- aerosolized powders (insufflators) for ear, nose, throat, lung (ex- Tinactin, Alupent)
- inhalation powders (ex- Advair diskus)
5
Q
Micromeritics
A
The science and technology of small particles
6
Q
Particle size influences:
5
A
- dissolution rate (solutions): Noyes-Whitney equation
- suspendability (suspensions)
- penetrability (inhalants): 1-10 um, <0.5 um gets exhaled
- grittiness (topicals): <44 um
- uniformity
7
Q
Comminution definition
A
reduction of particle size
8
Q
Trituration, comminution
A
mortar and pestle to reduce particle size
9
Q
Levigation
A
ointment preparation (powder + levigating agent to paste, trituration, + ointment base)
10
Q
Comminution types (2)
A
- trituration
2. levigation
11
Q
Blending powders
A
creation of uniform mixture
12
Q
Spatulation
A
smear on tile
13
Q
Trituration, blending
A
geometric dilution (equal volume drug and solvent, mix, add second volume…)
14
Q
Sifting
A
mix by sifting
15
Q
Tumbling
A
mix in rotating chamber
16
Q
Blending types (4)
A
- spatulation
- trituration
- sifting
- tumbling
17
Q
Powders and granules are used to prepare:
3
A
- tablets, capsules
- solutions, suspensions
- creams, ointments
18
Q
The size and size range of particles can impact the physical, chemical, and pharmacological properties of a drug
A
:)
19
Q
Important properties of polydisperse particles (2)
A
- number/weight and size
2. shape and surface area
20
Q
fine powders, size
A
50-100 um
21
Q
coarse powders, size
A
150-1000 um
22
Q
granule, size
A
1000-3360 um
23
Q
Particle Number (N)
A
number of particles per unit weight
24
Q
Coefficient of Variation (%CV)
A
100 / [ (N)^(1/2) ]
want large N, small %CV
25
Properties affected by particle shape:
| 3
1. packing
2. flow
3. surface area
26
Properties affected by surface area per unit weight/volume:
| 2
1. dissolution rate
| 2. surface adsorption
27
For a perfect sphere, as/av =
6
28
Pores impact:
| 2
1. dissolution and therefore
| 2. adsorption
29
Sw units
surface area per unit weight
| cm^2/g, um^2/g...
30
Sv units
surface area per unit volume
| cm^-1, um^-1...
31
bulk volume
total volume (particles + empty space)
32
true volume
volume of only particles
33
void volume
volume of empty space between particles
34
real porosity range
30-50%
35
true density
density calculation using true volume (does not include empty space)
36
bulk density
density calculation using bulk volume (includes empty space)
37
angle of repose estimates:
flowability of a powder
| measures frictional forces in a powder
38
flowability of a powder is affected by:
| 6
1. excipients (glidants)
2. particle size
3. particle shape
4. surface texture
5. porosity
6. density
39
Lipinski's Rule of 5
Poor absorption/permeation if:
1. > 5 H bond donors
2. > 10 H bond acceptors
3. log P > 5
4. MW > 500
40
Advantages of compressed tablets
| 6
1. simple, convenient
2. accurate dosage
3. control rate
4. more stable than liquid
5. uniform product
6. easy and cheap mass production
41
Essential properties of tablets
| 6
1. uniform weight, diameter, appearance
2. stable to air, moisture, temperature, light
3. withstand normal transport and patient handling
4. known strength
5. readily disintegrate in stomach
6. dissolve in gastric/intestinal fluids
42
separate different drug agents in a Multiple Layer Tablet due to:
(3)
1. drug incompatibility
2. staged release
3. unique appearance
43
Multiple layer tablet example
Gaviscon
44
Tablet within a tablet example
Vimovo (naproxen core surrounded by esomeprazole)
45
Advantages (3) and disadvantages (2) of sugar-coated tablets
Advantages:
1. protect drug
2. conceal taste
3. imprint info
Disadvantages:
1. increased time and expertise to manufacture
2. increase tablet size (up to 50%)
46
Sugar coated tablets examples
Advil, M.Ms, Skittles
47
Film coated tablets, plus advantages over sugar coated (3)
compressed tablet surrounded by thin polymer; more durable, less time-consuming, less bulky than sugar-coated
48
Film coated tablets examples
Tylenol film coated, Xarelto
49
Gelatin coated tablets, plus advantages over sugar coated (3)
compressed tablet with gelatin; gelatin facilitates swallowing, less bulky, more tamper evident
50
Gelatin coated tablets example
Tylenol gel tabs
51
Enteric coated tablets/capsules used for drugs that are:
| 3
1. destroyed by gastric acid
2. particularly irritating to gastric mucosa
3. has substantially enhanced absorption if stomach is bypassed
52
Enteric coated tablets/capsules examples
aspirin (stomach irritant), omeprazole/esomeprazole (are acid activated--prevent early activation), fish oil (prevent stomach digestion and fish burps)
53
Lozenges
at least 18 mm in diameter, do not contain disintegrant
54
Two types of lozenges
1. Local effect (ex- Sucrets)
| 2. Systemic effect (ex- Fentanyl)
55
Effervescent tablets
improve palatability; combination of alkali carbonates/bicarbonates and tartaric/citric acid--quick dissolution of active ingredient with liberation of CO2
56
Immediate release tablets
designed to disintegrate and release drug with no special rate controlling features
57
Rapidly dissolving tablets (RDTs)
designed to disintegrate/dissolve within 1 minute; very water soluble excipients; prepared by soft compression, lyophilized foam (freeze drying)
58
Disadvantages of RDTs (5)
1. drug loading
2. taste masking
3. friability
4. stability
5. manufacturing costs
59
drug loading
ratio of active drug to total components in a dosage form
60
friability
tendency to crumble
61
RDT preparation: Soft compression
compressed thinner than regular tablets (more surface area); super disintegrant excipients (wick water into tablet) plus effervescence to increase tablet disintegration (ex- Rolaids softchews, Dimetapp ND)
62
RDT preparation: Lyophilized foam
foam is lyophilized (freeze-dried) into tablets; fastest disintegration (ex- Claritin Reditabs, Zofran ODT, Maxalt MLT)
63
Advantages (2) and disadvantages (4) of extended/controlled release tablets
Advantages:
1. reduced side effects (esp for drugs with narrow therapeutic windows)
2. decreased frequency of dosing (improved adherence)
Disadvantages:
1. slow clearance
2. overdosing
3. large tablet size
4. cost
64
Vaginal tablets examples
Vagifem (estrogen), Mycelex G clotrimazole (yeast infection)
65
Implants
small pellets (2-3 mm); no excipients
66
Implants example
Testopel testosterone (males more noncompliant, daily gel reminds them of testosterone deficiency)
67
Powder fluidity and compressibility are important for tablet formulation. How to increase fluidity and compressibility?
Granulation improves both fluidity and compressibility
68
Tableting methods (3)
1. Wet granulation: wet mass is forced through sieve producing wet granules, recrystallization upon drying
2. Dry granulation: granulation by compression or roller compaction
3. Direct compression (dry): compress directly
69
Quality standards and compendial requirements of compressed tablets (6)
1. content uniformity (within 85-115% of label claim, <6% standard deviation)
2. weight/weight variation
3. thickness
4. hardness/friability (minimum 4 kg of force, <1% loss)
5. disintegration
6. dissolution
70
Extended release definition
allows a reduction in dosing frequency
71
Delayed release definition
designed to release at a time other than immediately after administration
72
Which drugs are candidates for extended release?
| 5
1. for chronic rather than acute conditions
2. neither very slow nor very fast absorption and excretion
3. uniform absorption (otherwise too unpredictable)
4. good margin of safety
5. relatively small doses (so it's not a huge tablet)
73
Methods of achieving controlled-release:
| 4
1. Diffusion-controlled release: insoluble matrix or coating (ex- Choledyl)
2. Dissolution-controlled release: water-insoluble carrier, coat individual drug granules, reduce disintegrating agent, (ex- Dimetapp extentabs)
3. Ion exchange-controlled release: drug is released in a high concentration of charged ions in GI tract (ex- Tussionex tablets)
4. Osmotic pressure-controlled release: release by osmosis (ex- Procardia XL)
74
Hard capsule
2 pieces, produced empty and later filled; contain 13-16% moisture; filled with dry solids (powders, granules, tablets) and semisolids
ex- Amoxil, Prozac
75
Soft capsule
manufactured and filled all at once; include plasticizers for softness and flexibility (glycerol, etc); roughly 1:1 water to gelatin; filled with liquid; often used to improve dissolution rate and bioavailability
76
Capsule
package made of gelatin
77
What is the most important factor to ensure uniformity of the filled capsule, and how can it be improved (3 excipient types)?
powder flowability
improved by:
1. diluents (ex- starch)
2. glidants (ex- fumed silicon dioxide)
3. lubricants
78
Advantages of soft capsules (4)
1. poorly compressible drugs
2. poorly soluble drugs
3. drugs with low bioavailability
4. drugs sensitive to oxidation or hydrolysis (oil dispersion)
79
Things you cannot put in a soft capsule:
| 4
1. water content >5%
2. extremes of pH (2.5-7.5 okay)
3. emulsions
4. aldehydes ("tanning" effect)
80
surface area of intestinal epithelium
200 m2
81
esophageal transport time
upright: 10-14 sec
supine: 300 sec
82
stomach transit time
minutes up to 2 hours
83
Where does tablet disintegration and dissolution begin?
stomach (affected by pH)
84
Where does the majority of absorption occur?
small intestine (pH affects ionization, drugs with ionization constants near enteric pH may precipitate)
85
pH range of small intestine
duodenum: pH 4
ileum: pH 8
86
small intestine transit time
4 hours
87
opposing forces to GI permeability (2)
1. gut wall metabolism
| 2. efflux
88
Absorption in the colon is important for which formulations and compounds?
controlled release (continuous or pulsed); highly lipophilic drugs
89
Lactose advantages (4) and disadvantages (2)
Advantages:
1. pleasant taste
2. dissolves quickly
3. absorbs little moisture
4. chemically neutral
Disadvantages:
1. poor flow
2. cost
