11 Hypertension - Done Flashcards
(401 cards)
1
Q
Define hypertension
A
High blood pressure
2
Q
Define cardiovascular disease (CVD)
A
Includes all the disease of heart and blood vessels
3
Q
Define cardiovascular risk
A
The likelihood of developing angina,myocardial infarction or stroke
4
Q
What is blood pressure?
A
The force of the blood pushing against the walls of the arteries
5
Q
What is systolic pressure?
A
The pressure of blood in the vessels when the heart beats
6
Q
What is diastolic pressure?
A
The pressure between beats when the heart relaxes
7
Q
What is the unit blood pressure is measured in?
A
Millimeters of mercury/mmHg
8
Q
What is considered to be high blood pressure?
A
140/90mmHg or higher
9
Q
What blood pressure is considered to be prehypertension?
A
Between 120-139mmHg and/or 80/89 mmHg
10
Q
What is considered normal blood pressure?
A
Less than 120/80 mmHg
11
Q
What is the most common intervention in primary care?
A
Management
12
Q
What some risk factors of hypertension?
A
- age
- co-morbidities
- ethnicity
- family history
- gender (M>F)
- hypertension in pregnancy
- poor diet (too much salt)
- smokers
- e.c.t.
13
Q
What are the consequences of high blood pressure?
A
- stroke
- heart failure
- erectile dysfunction
- vision loss
- heart attack
- kidney disease/failure
14
Q
What is Left ventricular hypertrophy?
A
It is the thickening of the heart’s main pumping chamber and is a consequence of hypertension.
15
Q
What is a result of left ventricular hypertrophy?
A
The thickening of the wall may result in elevation of pressure within the heart and sometimes poor pumping action
16
Q
How do we estimate CVD risk?
A
QRISK3-risk calculator
17
Q
What is the QRISK3-risk calculator?
A
It calculates risk of having a ‘heart attack or stroke’ over the next ten years and is based on data from UK GPs
18
Q
What patients would use QRISK3-risk calculator?
A
This is for primary prevention patients
19
Q
What can consistently high blood pressure lead to?
A
Damage in the arteries and organs and is a leading cause of stroke, heart disease and kidney disease
20
Q
Why is lowering blood pressure significant?
A
By lowering blood pressure by even 5 mmHg can significantly lower the chance of developing serious health problems
21
Q
In 2017, what was the estimation of people in the UK have high blood pressure?
A
1 in 4 people, however, many people are undiagnosed
22
Q
What is the NHSE Ambition target for people being treated with hypertension?
A
80% of people to be treated to target by March 25
23
Q
What is the cause of PRIMARY hypertension?
A
In most cases (90-95%) there is no identifiable cause
24
Q
What are the causes of SECONDARY hypertension?
A
- diseases (e.g. chronic kidney disease, Crushing syndrome, Parathyroid disease)
- drugs (e.g. corticosteroids, decongestants, NSAIDs)
25
What are the symptoms of high blood pressure?
- dizziness
- headache
- vomiting, nausea
- blurred vision
- shortness of breath
But most people are ASYMPTOMATIC
26
What ways can hypertension cases be found?
- opportunistic (patients present in health care settings)
- proactive methods
- ambulatory blood pressure monitoring
27
What are the proactive methods of finding hypertension cases?
- NHS health checks
- Community Pharmacy case finding services
28
What is the NHS health checks for?
It is for adults in England aged 40-74
Designed to spot early signs of stroke, kidney disease, type 2 diabetes or dementia
29
What is the purpose of community pharmacy case finding service?
To identify people over 40y years old with high blood pressure, who have previously NOT had a confirmed diagnosis of hypertension
30
Describe ambulatory blood pressure monitoring (ABMP)
- takes blood pressure every 30 minutes (day and night)
- need at least 14 daytime readings for diagnosis
- mean daytime BP
31
Describe home blood pressure monitoring (HBPM)
- alternative to ABPM and is increasing in use
- Patient does BP monitoring for at least 4 days and ideally seven days
- 2 readings each morning and 2 readings each evening at least 1 minute apart
- Discard day one readings and then average BP from all other days
32
What are some tips for taking blood pressure?
- patient should be relaxed
- take the pulse for 1 minute
- the arm should be supported at heart level
- no talking with the back supported and feel flat on the floor
- take 2 or 3 readings
33
Give examples of lifestyle advice for all
- DASH eating plan
- exercise
- reduced dietary sodium intake
- moderation of alcohol intake as needed
- weight loss if warrented
34
What can be tested to flag target organ damage?
- urine
- blood tests
- eyes
- ECG
35
What would you look at in URINE to spot target organ damage?
- albumin - creatinine ration (ACR)
- haematuria
36
What would you look at in blood tests to spot target organ damage?
- electrolytes, creatinine, eGFR
- lipid profile
- liver function and thyroid function
- HbA1c
37
What would you be looking at in the eyes to spot target organ damage?
Examination of fundi for hypertensive retinopathy
38
What would you be looking at with an ECG to spot target organ damage?
- 12 lead ECG: looking for hypertrophy
- signs of ischaemic changes (arrhythmias)
39
How would you estimate cardiovascular risk in people aged 25-84 without CVD, CKD or familial hypercholesterolaemia?
QRisk3 tool valid for UK population
40
What is the treatment plan for a patient with a blood pressure reading of under 135/85 mmHg?
You would check at least every 5 years and more often if clinic BP is close to 140/90 mmHg
If there’s evidence of target organ damage, consider alternative causes
41
What is the risk of using beta-blockers and thiazides together?
Increase risk of diabetes
42
Wha can newer drugs used to treat hypertension offer?
Offer slightly better stroke risk reduction in high risk patients
43
What is the first line of treatments for hypertension?
ACD:
- ACE inhibitors or ARB
- Calcium channel blocks
- Thiazide-like diuretics
44
What is white coat?
Blood pressure higher in clinical settings
45
What is masked hypertension?
Blood pressure is higher at home
46
Give examples of ACE inhibitors
Perindopril & Ramipril
47
In hypertension, when is ACE inhibitors given?
First line in younger (<55 years) Caucasian people and people who are diabetic
48
Apart from hypertension, when is ACE inhibitors used?
Primary and secondary prevention of CVD, heart failure and diabetic neuropathy
49
What are some side effects of ACE inhibitors?
- dry cough
- renal impairment
- angio-oedema
- HYPERkalaemia
- HYPOnatraemia
50
What must be monitored when taking ACE inhibitors?
Baseline renal function and electrolytes (Na and K) and they should be rechecked 1-2 weeks after starting and after any dose increase
51
What should you avoid taking with ACE inhibitors?
Avoid K+ sparing diuretics and NSAIDs
52
What cautions must you take with ACE inhibitors?
- care with diuretic therapy
- caution aortic stenosis (postural hypotension)
- do not use in pregnancy
- contraindications include bilateral renal artery stenosis
53
ACE inhibitors are the leading cause of what?
Drug induced angio-oedema (incidence 0.1-0.7% of patients)
54
What do you usually see (signs) with angio-oedema?
- swelling of the lips, tongue, face and upper airway without itching or urticaria
55
What is urticaria?
Hives - itching welts
56
When does angio-oedema present after starting prescription?
Half of cases occur in the 1st week of starting but can occur at anytime (hours-years)
57
When does the swelling in angio-oedema develop?
Over mins-hours to a peak with each episode lasting 2-5 days
58
Why does ACE inhibitors cause angio-edema?
CLASS EFFECT
ACE inhibitors cause angioedema by blocking the breakdown of bradykinin, leading to its accumulation. Elevated bradykinin levels increase vascular permeability, causing fluid to leak into tissues and result in swelling.
59
What does bradykinin do?
It’s a potent endothelium-dependent vasodilator and mild diuretic which may cause the lowering of blood pressure
60
What is the incidence of cross reaction between ACEi and ARBs?
Low incidence
61
Give examples of angiotensin II receptor blockers (ARBs)
Irbesartan & Losartan
62
What are ARBs an alternative to?
Alternative to ACE inhibitors
- DO NOT use in combination
63
Who are usually prescribed ARBs (angiotensin II receptor blockers)?
For black patients of African or Caribbean origin (in preference to ACEi) WITH DIABETES
64
What are the side effects of ARBs?
- cough
- lower risk of angio-edema than ACEi
- renal impairment
- HYPERkalemia
- headache
65
Who is offered calcium channel blocker for hypertension?
First line treatment for non-diabeteic patients aged >55 or black African or Afro-Caribbean
66
What are the two distinct classes of calcium channel blockers?
Dihydropyridine & non-dihydropyridine
67
Give examples of dihydropyridine CCBs?
- amlodipine
- lacidipine
- lercanidipine
- nifedipine
68
What does Dihydropyridine do?
It causes vasodilatation of coronary and peripheral arteries and relaxes smooth muscles
69
Apart from hypertension, what else can dihydropyridine be used for?
Treatment of stable angina
70
What are some of the effects of dihydropyridine CCBs?
- flushing and headaches
- ankle swelling
71
Where are CCBs metabolized?
By the liver
72
What blood tests are needed for dihydropyridine?
No specific tests are needed
73
Give examples of non-dihydropyridines?
- phenylalkalamines (verapamil)
- benzothiazepines (diltiazem)
74
How does non-dihydropyridines work to lower hypertension?
- interferes with myocardial conduction
- slows the heart rate
75
What should you not combine verapamil with and why?
Because it is a non-dihydropyridine, it should not be combined with beta-blockers as it slows the heart
76
What condition should you not use non-dihydropyridine in?
Heart failure as it may cause contractility to be reduced
77
What is a common side effect of non-dihydropyridine?
Constipation
78
What else can non-dihydropyridine be used for?
Treat stable angina and for arrhythmias (rate control)
79
What steps in hypertension treatment is thiazide like diuretics offered?
Step 2 or 3
80
What thiazide-like diuretics would be prescribed?
Indapamide 2.5 od (or chlorthalidone)
81
When would thiazide like diuretics not be effective?
Poor renal function (eGFR <30 ml/min)
82
What do you need to be careful of when taking thiazide like diuretics?
- electrolyte disturbances (Na, K, Ca)
- renal impairment
THEREFORE baseline U&E tests must be don’t and repeat within 1 month
83
What are some side effects of thiazide like diuretics?
- may cause skin rashes
- may unmask/exacerbate gout
- increases risk of diabetes (esp. w/ beta-blockers)
- loss of efficacy in CKS (eGFR <30 ml/min)
- increase in urate, glucose and blood lipids
- HYPOkalaemia
84
What is a 4th line drug of choice to treat hypertension?
Spironolactone - aldosterone antagonist
85
What is the risk of taking spironalactone?
Risk of HYPERkalaemia and renal impairment
86
What effect does NSAIDs have on blood pressure?
Increases it
87
What is the dosing advice for spironolactone?
Low doses only - max dose 50 mg/day
88
What tests should be done when taking spironolactone?
Baseline U&E and repeat in 2-4 weeks
89
Apart form hypertension, what else an spironolactone be used for?
Also used in heart failure (max 50 mg/day) and ascites (higher doses may be Rx)
90
Give examples of loop diuretics
Furosemide & bumetanide
91
Compare the potency of loop diuretics to thiazides
Loop diuretics are more potent than thiazides
92
Apart from hypertension, when else can loop diuretics be used?
Used in pulmonary oedema or heart failure
93
What is the mode of action of loop diuretics?
Loop diuretics inhibit the Na⁺-K⁺-2Cl⁻ cotransporter in the thick ascending limb of the loop of Henle, reducing sodium, chloride, and water reabsorption. This leads to increased urine output and decreased fluid volume, helping to lower blood pressure and reduce edema.
94
What are some unwanted effects of loop diuretics?
- renal impairment
- electrolyte disturbances (Na+, K+, Ca++, Mg++)
- may exacerbate diabetes
- may lead to gout
95
What must be monitored when taking loop diuretics?
Monitor U&E baseline and within 1 month after starting
96
What do alpha blockers do?
Vasodilatation of vascular smooth muscle
97
Why must there be care with dosing of alpha blockers?
It can cause postural hypotension
98
What is the usual choice of alpha blockers?
Doxazosin
99
Apart from hypertension, what else can alpha blockers be used for?
Benign prostatic hypertrophy (BPH) - there are alpha receptors in the prostate and urethra
100
Give examples of beta blockers
Atenolol, bisoprolol and metoprolol
101
Are any beta-blockers cardio-specific?
No but they may be CARDIO-SELECTIVE
102
How effective are beta-blockers?
Not as effective at reducing stroke, MI and mortality (HTN patients) compared to other drugs
103
What cautions do you need to keep in mind regarding beta-blockers?
Caution in lung disease and diabetes
Contraindications with severe asthma
104
What are some of the side effects of beta-blockers?
- bronchospasm + potential bronchoconstriction
- vasoconstriction via blockage of B2-R
- increase blood lipids
- nightmares (lipid soluble)
- fatigue
- cold extremities
- impotence
105
Why does beta blockers have contraindications with severe asthma?
Beta blockers are contraindicated in severe asthma because they block beta-2 adrenergic receptors in the lungs, which are responsible for bronchodilation. By inhibiting these receptors, beta blockers can cause bronchoconstriction, worsening asthma symptoms and potentially leading to severe respiratory distress.
106
What other methods would specialists use/special situations to treat hypertension?
- vasodilators
- centrally acting vasodilators
107
What do centrally acting vasodilators do?
They work directly on the part of the brain that controls blood pressure and are also known as CENTRAL ALPHA ANTAGONISTS
108
Give examples of vasodilators and centrally acting vasodilators
Vasodilators: hydralazine & minoxidil
Centrally acting vasodilators: moxonidine & clonidine
109
What should you consider with hypertension in pregnancy?
Need to use medicines with safety
110
Give examples of medication you can prescribe in pregnancy with hypertension
- labetalol
- methyldopa
- nifedipine
111
What hypertensive medication should be avoided in pregnancy?
Avoid ACEi/ARB in pregnancy
112
Are NICE targets or order of medicines always appropriate?
No - adapt your management plan to the patient
113
For what types of patients may you have to adapt their management plan for hypertension?
- elderly (limited evidence age >80)
- frailty
- postural hypotension
- renal disease
- other cardiac conditions
- one medicine for two indications
114
What would you potential have to adapt in management plan of hypertension for patients who are frail?
May need to relax targets
115
What does postural hypotension increase the risk of?
- risk of falls
- dementia
- stroke
- all-cause mortality
- significant impact on activities of daily living
116
What is postural hypotension?
When you measure blood pressure lying/sitting vs standing, there is a sustained drop (SBP >20 mmHg and/or DBP >10 mmHg) within 3 minutes
117
What part of the management plan for hypertension would be changed for a patient with renal disease?
- blood pressure targets may be lower
- choice of medication for CKD rather than following ‘NICE’ order
118
What would you need to consider in the management plan of hypertension for people with cardiac conditions?
If medicines have prognostic benefit e.g. heart failure, secondary prevention of CVD
119
Give an example of when one medicine having two indications need to be considered
Beta-blockers in the rate control in atrial fibrillation with lower the blood pressure
120
What is the formula for blood pressure?
BP = CO x TPR
121
What is the formula for cardiac output?
Cardiac output = stroke volume x heart rate
122
What is stroke volume regulated by?
The ventricles
123
What regulates heart rate?
The SA node
124
What is Starling’s Law?
The stroke volume of the left ventricle will increase as the left ventricular volume increases due to the myocyte stretch. This links with the force of contraction.
125
Describe the RAAS system
Low BP Trigger: Kidneys release renin.
Renin Action: Converts angiotensinogen (from liver) to angiotensin I.
ACE Enzyme: Converts angiotensin I to angiotensin II (in lungs).
• Aldosterone: Increases sodium/water retention in kidneys (raises blood volume/BP).
• ADH Release: Promotes more water reabsorption in kidneys.
• RAAS Blockers: ACE inhibitors/ARBs reduce BP.
126
Describe the RAAS system
Low BP Trigger: Kidneys release renin.
Renin Action: Converts angiotensinogen (from liver) to angiotensin I.
ACE Enzyme: Converts angiotensin I to angiotensin II (in lungs).
Aldosterone: Increases sodium/water retention in kidneys (raises blood volume/BP).
ADH Release: Promotes more water reabsorption in kidneys.
RAAS Blockers: ACE inhibitors/ARBs reduce BP.
127
What is the effect of angiotensin II?
Angiotensin II Effects: Vasoconstriction (raises BP) & Stimulates aldosterone release (from adrenal glands).
128
How is the total peripheral resistance regulated?
Increases in Ang II —> increase in IP3 —> increases intracellular [Ca2+]
This causes constriction of arterioles and and increase in total peripheral resistance
129
How is preload regulated?
Constriction of venues via AT1-R
RAAS also facilitates Na+ and H2O retention
130
What is the role of aldosterone?
- activates cytoplasmic receptors
- these receptors bind to the nucleus
- increase expression of Na+ channels
- H2O and Na+ retention is aided by
131
What is the treatment of hypertension dependent on?
- age
- ethnicity
- co -existing diseases
132
What are the main classes of anti-hypertensives?
- ACE inhibitors, Angiotensin receptor blockers, renin antagonists
- calcium channel blockers
- diuretics (no longer frontline)
- beta blockers (no longer frontline)
- vasodialators
133
What would be the first line choice of antihypertensive for a patient with type 2 diabetes?
ACEi or ARBs
134
What would be the first line choice of antihypertensives for a patient under 55 and not of black family origin?
ACEi or ARBs
135
What would be the first line choice of antihypertensives for a patient age 55 and over?
Calcium channel blockers
136
What would be the first line choice for a patient who is black-African or Afro-Caribbean?
Calcium channel blockers
137
What happens when a patient takes their first dose of ACEi?
Hypotension
138
Who would ACEi not be as effective for?
Black African/Caribbean patients
139
What are ACEi contraindicated in?
Bilateral renal artery stenosis
140
Why are ACEi frontline treatments for diabetic patients?
No adverse effects on serum glucose/lipids
141
What do angiotensin receptor blockers do?
Block the actions of Ang II on AT1-R
(-ARTAN)
142
Give an example of an aldosterone antagonist
Spironolactone - used to treat hypertensive patients with primary aldosteronism
143
What is the mechanism of spironolactone?
- inhibits the ability of aldosterone to produce new Na+ channels
- loss of Na+ and H2O
- decreased preload and reduced blood pressure
144
What do the main classes of dihydropyridine target? (-DIPINE)
Targets L-type Ca2+ channels on smooth muscle of blood vessels
145
What do non-dihydropyridine such as phenylalkylamines and benzothiazepines target?
Target L-type channels in the heart and decrease the frequency and force of contraction
- less used to treat hypertension
146
What are some side effects of CCBs?
- flushing and headaches
- peripheral oedema
147
What is the interaction between grapefruit juice and CCBs?
Grapefruit juice enhances action (CYP3A4)
-furanicomarins
148
Combinations of what is not recommended in regards to CCBs?
Combinations of Ca2+ channel antagonists are not recommended
149
What is peripheral oedema?
Impairment of the function of the pre-capillary sphincter increases hydrostatic pressure across the capillary and reduces fluid reabsorption
150
When would furosemide be used?
ONLY in resistant hypertension
151
What is the mode of action of thiazide-like diuretics?
• Inhibit the sodium-chloride symporter (NCC) in the distal convoluted tubule
• Decrease reabsorption of sodium and chloride
• Increase excretion of sodium, chloride, and water
• Reduce blood volume and lower blood pressure
• Mild vasodilatory effect contributes to antihypertensive properties
152
What is the mode of action of beta-blockers?
• Block beta-adrenergic receptors (mainly β1 and β2)
• Reduce the effects of adrenaline and noradrenaline
• Decrease heart rate (negative chronotropic effect)
• Reduce the force of heart contractions (negative inotropic effect)
• Lower blood pressure by reducing cardiac output and renin release from kidneys
153
Describe the link between beta-blockers and hypoglycemia
- blood glucose is low it activates the release of adrenaline, mobilizes glucose release from the liver
- beta blockers block this process
154
What are some symptoms of hypoglycemia?
- tremor
- palpitations
- sweats
- feeling tired or weak
155
“Combining **X** with beta blockers should be used with caution for diabetic patients.”
What is X?
Thiazides
156
Give an example of a non selective (B1 & B2) beta blocker
PropranOLOL - you wouldn’t give this to a patient with serious asthma as it is associated with asthma attacks
157
Give an example of a selective B1 antagonist
AtenOLOL
158
What are A1 antagonists?
Vasodilators
159
What are vasodilators?
- Used to treat hypertension in patients with benign prostatic hypertrophy
- Other vasodilators open K+ channels
160
Give an example of a vasodilator used to treat hypertension in patients with benign prostatic hypertrophy
doxAZOSIN
161
Give an example of a vasodilator used to open K+ channels.
minoxidil
162
What is the mechanism of action of amlodipine in the treatment of hypertension?
CALCIUM CHANNEL BLOCKERS
- Inhibits the influx of calcium ions into vascular smooth muscle and cardiac muscle cells.
- Causes vasodilation by relaxing smooth muscle in the arterial walls.
- Lowers peripheral vascular resistance, leading to reduced blood pressure.
- Has minimal effects on heart rate or cardiac contractility at therapeutic doses.
- Primarily acts on the peripheral vasculature, making it effective for long-term blood pressure control.
163
Spironolactone being prescribed depends on what?
Potassium levels
164
What is a particle?
Any unit of matter having defined physical dimensions, not a molecule
165
Solids are not what?
Static systems
166
What can alter the physical state of particles?
Physical manipulation
167
What is the lifetime of a drug?
1. Drug synthesis
2. Development of formulated medicine
3. Production of formulated medicine flow and packing properties
4. Administration of medicines
5. Drug in body
6. Drug removed from body
168
What implications does particle size have for tableting and capsule filling?
Particle size can affect flow properties of a powder and its packaging properties which has implications since machinery relies on a set volume entering the die at a given time. This is to avoid filling problems
169
What 10 things can particles affect?
1. Rate of chemical reaction
2. Dissolution rate
3. Bioavailability (via dissolution rate)
4. Packing density
5. Flow characteristics
6. Suspendabilty
7. Texture
8. Deposition site in lung
9. Colour
10. Taste
170
What effect does surface area have on the rate of reaction?
- reactions with solids take place on the surface of the solid
- when the solid is split into several pieces, the SA increases which increases the area for the reactant particles to collide with
- therefore are more collisions and a higher chance of reaction
171
Particle size can affect the rate of a chemical reaction which in turn affects what?
The stability of a drug
172
What is dissolution rate?
The speed/rate at which a drug substance can dissolve in a medium
173
Micronisation of solid particle
can increase its dissolution
rate – why?
when particle size is reduced, the total effective surface area is increased and thereby dissolution rate is enhanced.
174
What can happen with excessive particle reduction?
This can cause particle to re-aggregate into larger molecules
175
How can you prevent re-aggregation of particles that have been reduced excessively in size?
They can be dispersed in polyethylene glycol (PEG), polyvinylpyrrolidine (PVP) dextrose or other agents
176
What two types of uniformity of distribution can particle size effect?
- drug in powder mixture
- drum of drug or excipient in warehouse
177
Flow characteristic can affect what?
content uniformity when the tablet die is filled by volume
178
What does suspendability affect?
The dispersion of the API in a liquid vehicle where they remain undissolved but evenly distributed
179
Does dissolution rate affect the solubility of solid particles?
No, because solubility is a concentration not a rate so would not be effected
180
What are two types of equivalent sphere diameters?
- projected area diameter (da)
- perimeter diameter (dp)
181
What are equivalent sphere diameters used for?
To describe irregular particles
182
The method used to measure particle size determines what?
The type of equivalent sphere diameters measured
183
What does sieving measure?
Measures sieve diameter, dA
Generally used for dr powders
184
What does mono size mean?
All particles are the same size
185
What are the different distributions shown on a histogram when showing the range of particle sizes?
- Normal distribution
- Bimodal distribution
- Positively/negatively skewed
186
Describe normal distribution on a histogram for particle sizes
Can be normally distributed about a central value where the MODE (peak frequency value) separates the curve into 2 equal halves.
187
Give examples of techniques used for particle sizing
- sieving
- microscopy
- sedimentation rate
- electrical sensing zone method
- laser diffraction
- photon correlation spectroscopy
- cascade impaction
188
The choice of particle sizing depends on what? (5)
1. Size range of the particles to be measured
2. Wet or dry methods
3. Manual or automated methods
4. Cost of analysis
5. Speed of analysis
189
What does the range of analysis for microscopy measure?
Measures projected area diameter (da), perimeter diameter (dp), Feret’s diameter (dF) and Martin’s diameter (dM)
190
Why is it important that the particles in a powder mixture are the same size?
It would affect dosage
191
What are powders?
Solid particles of the same or different chemical composition
192
Why are powders so important?
Virtually all pharmaceutical preparations involve handling of powder ingredients at some stage e.g. tablets, hard capsules, solutions/suspensions and creams
193
Why is it important that powders have good flow properties?
So they can be packaged quickly and the dosage is uniformed
Free flowing order —> same volume
It also affects the mechanical strength of the tablets and encourages good content and weight uniformity
194
What is the importance of characterization in regard to powder flow?
It enables batter prediction for flow which is important for powder handling, equipment design & predicting formulation behaviour early on in the formulation process
195
How can flow behaviour be modified?
It can be made to flow better by adding excipients (e.g. glidant) or changing the size/shape of the powder particles
196
What are the forces acting in powder flow with examples?
DRIVING FORCES; gravity, mechanical forces etc.
DRAG FORCES: cohesion, adhesion, friction, surface tension
197
What is cohesion vs adhesion?
Cohesion is when the particles stick to each other which adhesion is the particles sticking to a surface
198
List some factors affecting powder flow?
1. Particle size
2. Particle shape
3. Particle density
4. Packaging geometry
5. Moisture content
6. Electrostatic forces
199
How does particle size affect particle flow?
The larger the particle, the better the flow as they have a SMALLER surface area, therefore lower cohesion/adhesion forced and gravity has a greater influence leading to better flow
200
How does particle shape affect flow?
Spherical particles have a better flow as they have smallest SA to volume ratio, less adhesion/cohesion and less friction.
Irregular shaped particles have larger SA, greater cohesion/adhesion, mechanical locking which lead to poor flow
201
How does particular density lead to better flow?
Denser particles lead to better flow as they are generally less cohesive than particles of lower density. More gravity acts on them as a driving force for powder flow.
202
What’s the equation for particle density?
Particle density (p) = particle mass (m)/particle volume (v)
203
What is packing geometry affected by?
- particle size and size distribution
- particle shape and texture
More tightly packed powders require a higher diving force to produce powder flow
204
How does packing geometry effect flow?
Looser packing leads to better flow
Particles closer together, greater cohesion/adhesion (van der Waals)
205
Define packing
Position of particles relative to each other in a defined volume
206
What is true density (p)?
- characteristic of individual particles
- mass per unit volume (g/cm3)
- intrinsic property of the material
207
What is bulk density?
- characteristic of the powder as a whole
- linked to porosity
- mass of powder/ bulk (fluff) volume (kg/m3 or g/cm3)
- The higher the porosity (spaces between particles the lower the bulk density)
208
What impact does moisture content & electrostatic forces on flow?
high moisture & electrostatic forces lead to poor flow as it makes the powder particles more cohesive
209
How can we measure powder flow if it is good or bad?
1. Angle of repose
2. Bulk density (packing geometry)
- Carr’s index (of compressibility)
- Hausner ration
3. Shear strength
4. Flow rate through orifice
210
What is the equation for the angle of repose (AOR)?
a = Tan -1 (h/r)
h = height
r = radius
a = AOR
211
Describe the link between AOR and co(ad)hesion
MORE CO(AD)HESION: stacks up, steeper slope, larger AOR and poor flow
LESS CO(AD)HESION: slides down slope, less steep slope, smaller AOR and better flow
212
What can you use to measure AOR?
- static AOR
- drained AOR
- dynamic AOR
Different methods and handling may produce different values for the same powder
213
What is the equation for bulk density?
Bulk density = mass of bulk powder (MB)/volume occupied by the bulk powder (VB)
214
Why is bulk density < true density?
This is because bulk density = k x true value where k is the packing fraction and is the void space as particles cannot fill the volume 100%. As k is variable so is bulk density
215
What does bulk density measure?
Measures how readily/to what extent a powder consolidates as consolidated powders flow poorly
216
What would you use to quantify bulk density?
1. Hausner ratio
2. Carr’s index (of compressibility)
217
Why can Hausner ratio only be bigger than one?
As fluff volume can never be smaller than tapped a when tapped the volume decreases.
You want the value to be as close as possible to 1
218
“The higher the Hausner ratio, the ____ the flow.”
Poorer
219
What is the equation for Hausner ratio?
Tapped bulk density/ fluff bulk density
OR
Fluff bulk volume/tapped bulk volume
220
“The ____ the Carr’s index, the ____ the flow
Higher & Poorer
221
“The ____ the Carr’s index, the ____ the flow
Higher & Poorer
222
What is the equation for Carr’s index?
100 (VF - VT)/VF
VT = tapped volume
VF = fluff volume
223
In regards to shear strength, what is shear cell?
Measures shear strength of powder bed —> powder cohesion/adhesion
224
What is the general rule of shear strength?
Greater shear strength —> more cohesive —> poorer flow
225
What is flow rate through orifice?
It’s the amount (mass/volume) of powder discharged through an orifice from a hopper, per unit time
226
For flow rate through an orifice, what is the general rule?
The higher the flow rate the better the flow
227
Flow rate through orifice is influenced by what?
- orifice diameter
- hopper wall angle
- hopper width
- height of powder head
228
How can we improve powder flow?
1. Use larger particles (granulation or remove fine particles)
2. Use more spherical particles (spray drying)
3. Avoid/remove electrostatic charges (earthing)
4. Remove excess moisture )drying)
5. Add a glidant (colloidal SiO2 to the powder mixture
229
How can we improve powder flow?
1. Use larger particles (granulation or remove fine particles)
2. Use more spherical particles (spray drying)
3. Avoid/remove electrostatic charges (earthing)
4. Remove excess moisture )drying)
5. Add a glidant (colloidal SiO2 to the powder mixture
230
How do glidants wok?
They work by reducing friction or cohesion between particles or by making the powder particles more spherical. However, there is a certain range of conc and once above this, they will inhibit powder flow
231
What is a capsule?
Solid dosage form, shells obtaining active ingredient
232
What are capsules used for?
Mostly for oral administration but may be formulated for other routes such as inhalation, rectal or vaginal
233
What are the two main types of capsules?
Hard & soft (softgels)
234
Describe the shell material of hard capsules
- 2 piece hard shell
- contains gelatin, water, opacifier, plasticiser and surfactant
235
What are the basic features of a hard capsule?
Cap and body
The body is smaller in diameter, longer and inserts into the cap
236
What are some advanced features of hard capsules?
*look back at lecture for their benefits
1. Tapered trim
2. Notches/dimples
3. Circle grooves
4. Air vent
237
How are hard capsules made?
1. Dip metal pins in gelatin solution
2. Dry to form capsule halves
3. Remove from metal pins
4. Trim to desired size
5. Assemble for transit
238
What is gelatin?
Hydrolysed collagen derived from connective tissue such as skin, bone and ligaments
239
What are the two types of gelatin?
A Acid-hydrolysed
B Alkali-hydrolysed
240
What are some alternatives to gelatin?
HPMC or PVA
hydroxypropyl methylcellulose or Polyvinyl alcohol
241
Give examples of fill material
- powder
- granules
- pellets
- liquid
- tablets
- capsule
- there are filling combinations
242
What are the requirements for the filling material for capsules?
- homogeneity
- physicochemical properties
- capsule size
- flow properies
243
What are the two types of dosing systems?
Dependent and Independent
244
What is dependent dosing systems?
The capsule body volume is used for accurate filling
245
What is independent dosing systems?
It’s when the fill material is weighed independently of the capsule body volume
246
What are two examples of independent dosing systems?
1. Dosator - measures the exact mass of powder using a dosing tube in a dosing chamber
2. Tamping fingers - force plugs (compacted powder) through holes in dosing disc
247
What are the advantages of hard capsules?
- versatility
- product stability
- product efficiency
- clinical trial blinding
- user acceptance/adherence
248
Give examples of types of soft gels
- orally administered
- chewable
- suckable
- twist-off
- meltable
249
Describe the shell material of soft gel capsules
Continuous one piece of gelatin
Usually ovoid or oblong
250
How is dry cough produced by ACEi?
Ace enzyme converts Ang I —> Ang II and breaks down bradykinin to inactive peptide
ACEi reduce production of Ang II which reduces the conversion of bradykinin to inactive peptide —> this reduces irritation which reduces production of dry cough
251
How is total peripheral resistance regulated?
Increase in Ang II -> bins to AT 1 receptors which is coupled with G protein —> increases IP3 —> increases intracellular Ca —> calcium binds with calmodulin —> actives actin and myosin —> cross bridges made leading to contraction of smooth muscle of arterioles —> increase in TPR —> increase in BP
252
What are the fill materials of soft capsules?
- drug in lipophilic solution/suspensions
- drug in hydrophilic solution/suspensions
- self-emulsifying systems
- lipolysis systems
253
What is a self-emulsifying system?
Concentrates of drug-oil-surfactant form micro/nano sized droplets instantaneously in contact with GI fluid
254
What are lipolysis systems?
Lipid bases matrix susceptible to lipolysis in the GI tract which results in enhanced drug dissolution in lipolysis products facilitates absorption.
255
What requirements must the fill matrix meet?
- dissolves/suspends drug
- disperses drug following softgel rupture in GI tract
- it retains drug in solution in the GI tract
- it’s compatible with softgel shell
- enhances drug absorption characteristics
256
What are some advantages of soft capsules?
- improved drug absorption
- user preference/adherence
- enhanced safety in manufacture or handling
-provided ideal formulations of oily drug
- dose uniformity
- dose stability
257
What are the quality parameters when producing softgel capsules?
Impurities in gel (e.g. aldehydes)
Gel ribbon thickness
Shell seal thickness
Fill matrix weight
Shell weight
Shell moisture content
Shell hardness
258
What are the in-process control parameters when producing soft gelatin capsules?
1. Gelatin viscosity and thickness
2. Temperature
3. Capsule sealing
4. Filling accuracy
5. Rotary die speed
6. Drying conditions
7. Moisture content
259
What is a tablet?
A solid dosage form containing a single dose of one or more API and suitable formulations aids (excipients)
260
How are tablets manufactured?
Usually by compression
Other techniques: extrusion, moulding, lyophilization and 3D printing
261
What are tablets usually used for?
Usually used for oral administration of drugs for systemic delivery by some are used for oral action
262
What are the components of a tablet?
Active pharmaceutical ingredient & excipients (binder, glindant, lubricant, filler)
263
What are excipients?
Inert substances used as formulation aids
264
What percentage of API would be considered a high dose and a low dose?
Low dose: <5% of tablet weight
High dose: >50% of tablet weight
265
What is the function of tablet excipients?
Aids the production of tablets with required quality specifications such as:
- content uniformity
- stability of API and finished product
- enhancement an control of bioavailability
- smooth operation of the tableting procedure
266
What properties should tablet excipients have?
- non-toxic
- inactive (chemically and physiologically)
- cost effective
- required physiochemical properties
- correct standard/quality
267
What is bulking agent used for?
Used to increase bulk volume of powder when handling small quantities of API.
This helps increase tablet size to make it suitable for processing and manufacturing
268
Binding of the drug to the filler may affect ___
Bioavailability
269
Give examples of filler or dilutent
- lactose (not suitable for lactose intolerant people)
- sucrose, glucose, mannitol
- cellulose
- inorganic
270
What is binder used for in making tablets?
For production of granules and tablets of required mechanical strength and is added to drug-filler powder mix before granulation
271
What does binder improve when making tablets?
Improved flow properties by formation of granules and ensure tablet integrity after compression
272
What is the typical conc. of binder and what would happen if you went over or below?
Typical conc. 2-10% w/w
Insufficient binder conc. - production of weak tablets
Excessive amounts - tablets may be too strongly bound
273
If a tablet is too strongly bound what effect would this have?
- negatively impact dissolution and drug release from the tablet
274
For binders, what are the two modes of addition?
As a dry powder or as a solution
275
What is glidant used for?
Used to increase flow ability of powder mixture and is added to granules before tableting to ensure optimum flow ability for high-speed production runs
276
What does glidant improve and how?
Improves powder flow by reducing friction between particles, cohesion and surface charge
277
What is the role of lubricant? (3)
- help reduce friction between the tablet surface and the die wall
- ensures smooth formation and ejection of the tablets and reduces wear on tablet machine’s punches and dies
- prevents capping, fragmentation or scratches which can effect the quality of the tablet or halt production
278
Are lubricants hydrophobic or hydrophilic in nature?
Hydrophobic
279
What would happen if lubricants when making tablets were in high concentrations?
They would slow down tablet disintegration and dissolution
280
What is the function of antiadherent?
Reduces adhesion between powder and punch surface, preventing sticking or picking
281
What is picking?
When there is a build up of thin powder layer on punches which results in uneven and matte surfaces with unclear symbols and markings
282
What is the function of flavour in making tablets?
Used to improve or mask unpleasant taste
283
When making tablets, why must flavour be added before processes that involve heat?
They are frequently THERMOLABILE - sensitive to heat
284
What is the function of colourant?
Improves tablet appearance
Helps with identification and adherence
285
What does disintergrant do in tableting?
Facilitates break up (deaggregation) of tablet compact into smaller components when in contact with liquid
286
Why is deaggregation of tablets important?
It increases the exposed surface area to GI fluids which enables faster drug release and dissolution
287
What are the modes of action of disintergrants?
- facilitates water uptake which leads to deaggregation —> tablet rupture occurs which is the mechanical consequence of water uptake
- production of gas - releases gas in contact with water e.g. effervescent tablets
288
What are two types of releases of tablets?
Immediate release and modified release
289
Give examples of immediate release tablets?
Disintegrating
Chewable
Effervescent
Sublingual
Buccal
290
Give examples of modified release tablets
Prolonged release
Pulsatile release
Delayed release
291
Why is sublingual or buccal administration beneficial for drugs with high first-pass metabolism?
It’s good for drugs with high first pass metabolism so you can bypass it by making it enter the bloodstream within the vessels in the mouth
292
Why would excipients in specialised tablets be different?
Because it would be absorbed differently
You would need to consider how quickly we would need the API and how long you would like the effect
293
What are the advantages of tablets?
- oral delivery with is safe and convenient
- stability
- dosage form containing accurate doses of drug can be reproduced
- mass produced at a low cost
- versatility and convenience
294
What are the disadvantages of tablets?
- compression difficulties due to powder physical properties
- poor/variable bioavailability
- unsuitable for some patients
295
When manufacturing tablets what qualities must powders have?
- COMPRESSIBLE - when subjected with force from the punches, the particles must cohere to form a compact
- able to MAINTAIN THE COMPACT - must remain as a tablet without breaking up when removing the punch
296
What is the manufacturing process?
Weighing —> mixing —> granulation —> tableting —> coating —> quality control (uniformity of mass —> dissolution)
297
How are tablets formed through compression?
Pressure is applied to a powder for force particles close together by confined compression to cohere to form a solid compact of define geometry
298
What are some tablet machines?
- single punch
- rotary press
299
What are the two ways of preparing a powder for compression?
- granulation
- direct compression
300
What is the method of wet granulation when preparing powders for compression?
Adding solvent and binder to powder, mix, dry and break up through screen to produce particle aggregates
301
What is the tableting journey?
Mixing powders —> (granulation if needed) —> compression —> coating —> packing
302
What is comminution?
The process of converting solid particles from an initial (larger) size into a smaller size or size range and requires the application of mechanical force
303
Why is comminution important?
- tablet production uses solid particulate drugs and excipients and the raw materials often have larger particles than requires
- particle size has an effect on: material handling, manufacturing efficiency and biopharmaceutical properties
304
What is the effect of comminution?
- increases specific surface area
- improves content uniformity in tablets
- increases bulk density
305
What is the result of improving content uniformity in tablets?
- easier to distribute particles across entire volume when more subdivisions available
- more even (uniform) distribution of particles within tablet
306
For a given mass, the smaller the particle size leads to…
… more subdivisions and the larger the specific surface area will be
307
In what two ways will particles within a batch vary in size and what would effect them?
- central diameter (e.g. mean, mode, median)
- distribution (e.g. standard deviation, range)
BOTH affected by comminution
308
Comminution starts with _____ _______ and initiates _____ _______ explained by ______ _______ of brittle fractures
1. Crack propagation
2. Particle fracture
3. Griffith’s theory
309
What would different particles of offered sizes exhibit?
- different fracture behaviours and is susceptible to various extents to the effect of a comminution method
310
What does Griffith’s theory describe?
describes the mechanism of brittle fractures
- material have microscopic flaws
- energy applied during comminution concentrated at tip of crack
- energy at crack tip overcomes bond strength
- bond rupture cascades along region with most flaws to dissipates energy
- almost instantaneous brittle fracture
311
What are some of the various equipment and techniques of comminution?
- cutting
- compression
- impact
- attrition
312
What should you consider when hosing a method of comminution?
- target particle size
- material properties
- cost (smaller target size is generally more costly)
313
What is toughness is regard to material properties for comminution?
Ability to absorb energy by deforming
- tough (non-brittle) materials are difficult to comminute
314
What is surface hardness in regard to material properties for comminution?
Ability to resist permanent deformation
- hard materials are difficult to comminute, may damage equipment parts
315
What is mixing?
Combining particles of different ingredients which are initially separated or partially much such that each particle of one ingredient will be positioned as close as possible to a particle of each of the other ingredients.
316
What are the four degrees of mixing?
1. complete segregation
2. Partial mix
3. Ideal or perfect mix
4. Random mix
317
Why do we need uniformity when mixing?
To avoid issue with therapeutic effects and safety/toxicity issues
318
How would you minimise content variation when mixing and remain with acceptable limits?
- increasing proportion of drug particles relative to excipients in mixture
- increasing total number of particles in mixture (e.g. comminution)
- using an efficient mixing procedure
319
What is powder segregation?
Demixing - separation of components
Where random mix becomes a non-random mix or there is a failure to achieve. Random mix
320
When would powder segregation occur?
Can occur due to handling due to the differences in particle properties
321
What is the effect of powder segregation?
Quality of mix is reduced, content variation and unacceptable weight variations
322
What is ordered mixing?
Adsorption of small (micronised) powder particles on larger particles
323
What are the effects of ordered mixing?
It minimises segregation and ensure good flow properties
Likely to occur in every powder mix
324
Describe pharmaceutical powder mixes
Partly random and ordered
325
Why is ordered mixing better than random mixing?
- beneficial for potent drugs
- direct compression tablets - prevents segregation
326
Give examples of when ordered mixing is used
1. Dry antibiotic (fine powder) formulation for reconstitution in water is adsorbed on the surface of sucrose or sorbitol (larger molecules)
2. Dry inhalation powder (micronised) adsorbed on larger carrier particles e.g. lactose
327
What are some examples of powder mixing?
- tumbling mixers
- agitator mixers
- fluidized bed mixers
- high speed mixer-granulators
328
What are the advantages of the direct compression method?
- no granulation process needed
- thus cheaper and preferred by manufactures
329
What factors would you need to consider when directly compressing tablets?
- % 250mg tablet
- content uniformity
- flow
- compaction
330
What are granules?
Aggregates of powder particles with a particle size of 200um - 4mm
331
What are the uses of granules?
- standalone dosage form
- intermediate product in tablet/capsule manufacture
332
Why do we granulate?
1. Prevent segregation
2. Improve flow properties
3. Improve compaction characteristics
4. Reduce fines (toxic drugs)
333
What are the types of granulation methods?
1. Wet granulation
2. Dry granulation
3. Melt granulation
334
What is wet granulation & the process?
Wet messaging using granulation fluid
1. Spraying with granulating fluid which is usually a volatile solvent with binder which evaporated as granules dry, leaving behind the binder holding them together
2. Agglomeration - particles collide and stick together
3. Finished granulate
335
What are the methods of wet granulation on a larger scale?
1. Low shear method
2. High shear method
3. Fluidised bed method
336
When would you use dry granulation?
When wet granulation is unsuitable for moisture/heat-sensitive materials e.g aspirin
337
What should you avoid in melt granulation?
Avoid use of water or organic solvents
338
The particle bonds for granulation must be what?
They must be strong enough to prevent granules from breaking down into powder during subsequent processes
339
The particle bonds for granulation must be what?
They must be strong enough to prevent granules from breaking down into powder during subsequent processes
340
What are the five primary bonding mechanisms for granulation?
1. Adhesion and cohesion in immobile films
2. Interfacial forces in mobile liquid films
3. Formation of solid bridges
4. Attractive forces between solid particles
5. Mechanical interlocking
341
How does adhesion/cohesion in immobile films result in granulation?
Adsorbed material e.g. moisture results in:
1. greater particle diameter, SA
2. Thus reduced inter-particulate distance
3. Resulting in greater van der Waals forces
342
What do interfacial forces in mobile liquid films give rise to?
Various states of inter-particulate water distribution
343
What are the states of inter-particulate water distribution from weakest interfacial forces to strongest?
Pendular state —> Funicular state —> capillary state
344
The stronger the interfacial forces, the ____ the granules
Stronger
345
Solid bridges can arise from what?
- hardening of binder
- crystallisation of dissolved substances following drying
- partial melting und pressure + solidification - dry granulation
346
What are the attractive forces between solid particles?
- van der Waals forces
- electrostatic forces
347
In mixing, van der Waals forces increases as what decreases?
Inter-particulate distance decreases e.g. applying pressure
348
What does electrostatic forces contribute to?
May contribute to initial agglomeration e.g. during mixing
349
How is drying powders and granules done?
- with controlled heat
- The energy input is to provide latent heat of vaporisation/sublimination with minimal temperature rise
350
What do you need to be cautious of when drying powders and granules?
Caution taken to minimise thermal degradation and to not cause unwanted effects on the API
351
What is FMC?
Free moisture content refers to unbound water which is readily removed by evaporation
352
What is EMC?
- Equilibrium moisture comtent refers to bound water which is difficult to remove by evaporation.
- Adsorbed/absorbed water exists in equilibrium with moisture in ambient atmosphere
353
What does EMC depend on?
- temperature
- relative humidity
- nature of solid
354
What is the equation for relative humidity?
RH (%) = p/ps x 100
p (Pa) = vapour pressure of water in air
ps (Pa) = Vapour pressure of water in air saturated with water vapour at same temperature (temperature-dependent)
355
During drying, what could change temperature and moisture content (therefore RH)?
- evaporated water from a drying solid
- evaporative cooling of air via latent heat transfer to drying solid
356
Once FMC is removed extended drying times will not remove ____ unless ____ is lowered
1. EMC
2. RH
357
How can relative humidity be lowered?
- air conditioning
- desiccators
358
Why do pharmaceutical solids work best with some residual moisture content?
Moisture prevents build up of statics in powders thus promoting flow
359
What are some methods of drying wet solids - granules?
- convective drying (gas)
- conductive drying (e.g. vacuume ovens)
- radiation drying
360
What would you need to consider when selecting a drying method?
- thermostability
- physical properties
- nature of liquid
- scale of operation
- need for asepsis/sterility
361
What are the principles of efficient drying?
- large SA for heat transfer
- efficient heat transfer
- efficient mass transfer
- efficient vapour removal
362
What solute migration?
Solute redistribution towards drying surface, following solvent movement (intergranular and intragranular)
363
What are the two types if solvent movement between solid particles?
IINTRAgranular and INTERgranular
364
What is solute migration affected by?
- granule formulation
- drying method
- moisture content
365
What is the effects of solute migration?
- migration of drug plus attrition leads to variability in drug content, thus drug loss
- migration of colouring leads to mottling
366
What is the feature of ordered mix?
It prevents segregation
367
Tablet compression is made up of what materials?
- granules
- primary powder particles (direct compression)
368
What are the processes of tablet compression?
- powder compression
- powder compaction
369
What is the process of tablet compaction?
1. Filling
2. Clearing excess powder
3. Compression
4. Ejection of tablet
370
What are two important powder characteristics?
Compressibility & compactibility
371
What is compressibility?
Propensity of powder to reduce in volume when subjected to pressure in a confined space
372
What is compactability?
Propensity to form coherent tablet when compressed
373
What is the mechanism of powder (granule) compression?
1. Reposition
2. Deformation
3. Fragmentation
4. Densification
5. Attrition
5. Deformation of primary particles in granules
374
Briefly list the tablet compaction cycle
1. Die filling
2. Tablet formation
3. Tablet ejection
375
What excipients can be added to aid the compression process?
- glidant
- lubricant/anti-adherent
376
What are the 5 bonding types in tablets according to Rumpf classification?
1. Solid bridges
2. Bonding by liquids
3. Binder bridges
4. Intermolecular and electrostatic forces
5 mechanical interlocking
377
Various dies and punches produce different tablet shapes, scoring, embossing etc. Why are these features important?
Helps with identification, and aid with accuracy in a pharmacy setting
378
Powder compatibility determines what?
- fracture tendency & mechanical strength of tablets (e.g. capping and lamination)
379
What is capping and what are the reasons for it?
Top of tablet separates from body.
Reasons:
- air entrapment
- fines deposition along upper edge of tablet
- insufficient moisture/binder
- poor mixing
380
What is lamination and what are the causes of it?
Splitting of tablet body, not limited to cap
Reasons:
- over compression
- poor powder cohesion
381
What is the definition of tablet coating?
Process by which an essentially dry outer layer of material is applied to a tablet surface
382
What are the uses of tablet coating?
- enhance tablet strength
- protect product (e.g. from light & moisture)
- protect handles (e.g. from toxic drug)
- modify drug release
- improve patient acceptability (e.g. taste, appearance, ease of swallowing)
- product identification
383
What are the methods of application of the coating material for tablets?
Poured & sprayed
384
What are the different types of coating?
1. Film coating
2. Sugar coating
3. Compression coating
385
Why might film coating be popular?
- thin and is negligible in thickness and mass
386
What are the main methods of coating?
Coating pan and fluidised bed coating
387
What are the two types of film coating?
1. Immediate release (non-functional) coating
2. modified release (functional) coating
388
What is the use of immediate release coating?
Used to modify appearance, taste or for identification
389
What is the use of modified release coating?
Used to modify release of drug from tablet
390
What is the difference between delayed release and extended release?
Delayed release medication is SELECTIVELY SOLUBLE at pH > 5-6 while extended release medication is relatively INSOLUBLE IN WATER and drug is usually released over 6-12 hours
391
What are the types of film coating polymers?
1. Immediate release (soluble in water, drug release quickly)
2. Delayed release (water soluble at high pH but to low pH, drug is released in intestines)
3. Extended release (relatively insoluble in water, drug released slowly)
392
What are the 5 film coating characteristics and why are they important?
1. Solubility - dictates bioavailability
2. Viscosity - ideal for spaying if low
3. Permeability - important for taste, drug stability and bioavailability
4. Strength and flexibility - must not crack easily
5. Adhesion - must not stick to tablet core and not peel of easily
393
What are some film coating defects?
1. Peeling
2. Orange peel effect
3. Mottling
4. Bridging
5. Core erosion
394
What is peeling in reference to film coating defects?
When film fragments flake off coated surface possibly due to excess moisture in tablet
395
What is bridging in reference to film coating defects?
Obscuring of indented markings
396
What is core erosion in reference to film coating defects?
Disfiguration of core due to overexposure to film coating solution
397
What is sugar coating?
Usually achieved by using a pan coating apparatus and creates a thick coat.
398
What are the stages of sugar coating?
1. Sealing
2. Sub-coating
3. Smoothing
4. Colouring
5. Polishing
6. Printing
399
Compare sugar coating to film coating
Sugar coating: round and polished in appearance, with a weighting increase of 30-50% with no embossed logo or breakline
Film coating: retains contour of core tablet and is less shiny in appearance, with a weighting increase of 2-3% with a possible embossed logo or breakline Film coating
400
Describe compression coating
It is a novel drug delivery application when two drugs are used (one in core tablet , other in coating)
It is dry with no heat coat for liable drugs
Fast and slow release components in the formulation
401
What is the process of compression coating?
1. Primary compaction
2. Transfer core tablet to larger die
3. Fill die around core table
4. secondary compaction
