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drugs with decreased dissolution
aspirin, phenobarbitone, phenacetin
drugs with increased dissolution
theophylline, nitrofurantoin
digoxin
grisefolvin (micropartilised)
desired API characteristics when developing an oral solid dosage form
Melting point >90 (degrees Celsius)
contact angle with water <90 degrees
Particle size 50-500microns
bulk density >0.3mg/mL
Describe the flow of blood through a glomerulus for USEFUL MATERIALS
Blood flows in via afferent arteriole→glomerulus which sits in the Bowman’s capsule (filtration occurs)→proximal convulted tubule→proximal straight tubule→useful materials reabsorbed via the vasa recta, also known as the peritubular capillary
Describe the flow of blood through a glomerulus for WASTE materials
Blood flows in via afferent arteriole→glomerulus which sits in the Bowman’s capsule (filtration occurs)→proximal convulted tubule→proximal straight tubule→loop of Henle→cortical and medullary connecting ducts
Where does glomerular filtration occur?
Bowman’s capsule only
drugs lost by renal elimination
- Acyclovir
- Ampicillin
- Cimetidine
- Metformin
Methotrexate in the kidney cells
1) Uptake transporter(s)
2) Efflux transporter(s)
1) OCT1 and OAT1
2) MRP4 and ABCB1 (P-gp)
Pitvastatin in the kidney cells
1) Uptake transporter(s)
2) Efflux transporter(s)
1) OAT3
2) ABCG2 (BCRP)
Rosuvastatin in the kidney cells
1) Uptake transporter(s)
2) Efflux transporter(s)
1) OAT3
2) ABCG2 (BCRP)
Fexofenidine in the kidney cells
1) Uptake transporter(s)
2) Efflux transporter(s)
1) OAT3
2) ABCB1 (P-gp)
Digoxin in the kidney cells
1) Uptake transporter(s)
2) Efflux transporter(s)
1) OATP1
2) ABCB1 (P-gp)
3 big groups of blending and mixing equipment
- Diffusion blending
- Pneumatic mixers
- Convection mixers
Examples of diffusion blending (tumble) equipment
- V blenders
- Double cone blenders
- Bin blenders
- Static continuous blenders
- Dynamic continuous blenders
Examples of Convection mixers (equipment)
- Diffusion blenders with agitator
- Vertical high intensity mixers
- Ribbon blenders
- Orbiting screw blenders
- planetary blenders
Diffusion bin blenders key parameters
- Fill volume 40-60%
- rotation speed (rpm)
- blending time (min)
- Number of revolutions=speedxtime
Dynamic continuous mixer
-enables fully continuous processing
-reduces segregation risk
Types:
-Weir design
-inclined design
why granulate?
- improve homogeneity
- improve bulk density (solids handling, packaging, transport)
- Deliver dissolution profile by manipulating structure
How can segregation happen?
- Fluidisation/eludritation - higher drag:weight ratio
- sifting (big particles at top - brazil nut effect)
- Trajectory (big particles go further than small particles)
Types of granulation (bigger topics)
- Dry granulation
- Wet high-shear granulator
- Wet low-shear granulator
- Low shear tumble granulator
- Extrusion granulation
- Rotary granulator
- Fluid bed granulator
- Spray dry granulator
- Hot-melt granulator
Types of dry granulation machines
- slugging
- roller compaction
types of wet high-shear granulators
vertical
horizontal
Types of wet low-shear granulators
- planetary
- kneading
- screw
Types of low-shear tumble granulators
- slant cone
- double cone
- v blender
types of extrusion granulators
- radial or basket
- axial
- Ram
- Roller, gear or pelletizer
Rotary granulator types
- open
- closed
Aims of solid fraction (solid to air proportion)
Powders: 0.2-0.5
Ribbons: 0.6-0.8
Tablet: 0.8-0.95
Types of high shear wet granulators
- Twin screw
- batch high shear
What happens in a high shear wet granulator?
- consolidation
- nucleation
- rate processes
- growth
- attrition
- breakage
Summarise rate processes
- wetting and nucleation
- consolidation and coalescence (agglomeration)
- attrition and breakage
Capsules vs tablets
Name 3 hard capsule advantages
- fewer excipients and formulation problems
- reproducible disintegration
- fewer manufacturing stages
Capsules vs tablets
Name 7 disadvantages capsules have compared to tablets
- lower production rate
- higher pack volume
- greater weight variation
- less protection to hygroscopic materials
- limited in size and shape
- capsule shell supplier dependent
- sensitive to extremes of temperature and humidity (brittle/soften)
Describe the capsule filling cycle
empty capsules→aligning and rectification→opening and separation→ filling→joining and closing→discharge