Dosage form design and Distribution of drugs around the body Flashcards
1
Q
What is the purpose of dosage form design?
A
To achieve a predictable therapeutic response (pharmacokinetic profile)
2
Q
What are exipients used for?
A
- Chemical and physical stability
- Preservation
- Uniformity of drug dose
- Acceptability to patient (compliance)
3
Q
What is excipient?
A
An inactive substance that serves as the vehicle or medium for a drug to other active substance
4
Q
What are the 4 dosage forms?
A
Aqueous solutions -> Aqueous suspension -> Capsules -> Tablets
5
Q
What is Aqueous solution?
A
A homogenous one-phase system consisting of two or more components
6
Q
Advantages of Aqueous solution?
A
- Paediatric and geriartic applications
- Drug is uniformly ditributed
- Drug is ready to be absorbed as it’s already dissolved
7
Q
Disadvantages of aqueous solution?
A
- Commerical viability
- Stability of ingredients
- Microbial growth
- Accurate dosing
- Addition of exipients to improve patient complianc and stability
8
Q
What is Aqueous suspension?
A
A dispersion of divided insouble solid particles in a fluid
9
Q
Factors affecting bioavailability from Aqueous suspension
A
- Particle size (SA)
- Complexation with exipients (Flocculating agent)
- Drugs needs to remain homogenous for dosing
- Drug need to be resuspended after storage
- Parenteral suspension must be isotonic and sterlie
- Tropical suspension must dry quickly and not rub off easy
10
Q
What is the advantages of Aqueous suspension?
A
- Low solubility dugs formuated in aqueous suspension
- Higher rate of bioavailability
- Faster absorption than capsules and tablets
- Mask bad taste
- Great for paediatrics and geriatrics
- Less hydrolysis
- Provide controlled release
11
Q
What is the disadvantages of Aqueous suspension?
A
- Pourability issues can affect dosing
- Formulation must b shaken prior to administration (Patient compliance)
- Suspensions are difficult to store
- Requires time and skill to formulate a suspension
12
Q
What are capsules?
A
Liquid filled into a degradable capsule
13
Q
How are capsules formulated?
A
Drug is dissolved or dispered in a liquid medium and contained in a capsule
14
Q
What happens when the capsule is consumed?
A
Release of drug occurs when the capsule dissolves or splits
15
Q
What kind of gelatine can capsules have?
A
Hard or soft
16
Q
How is bioavailability affected in capsules?
A
- Solubility of drug in vehicle
- Nature of the vehicle
- Particle size of the drug
17
Q
What are the factors affecting bioavailability in powder filled capsules?
A
- Surface are and particle size
- Aggregation of the powder
- Packing density of the capsule
18
Q
What exipients are used in powder filled capsules?
A
Wetting agents, bulking agents
19
Q
What are advantages of powder filled capsules
A
- Capsules - release the drug quickly c.f a tablet
- Tasteless, no need for flavourings etc
- Capsules have a higher bioavailability than tablets
20
Q
What are the disadvantages of powder filled capsules?
A
- Capsules have a shorter shelf life than tablets
- Capsules can be less stable in environmental conditions - packaging
- Some capsules are unsuitable for vegetarians
21
Q
What are tablets formed by?
A
Compression of powder held within a confined space
22
Q
How can tablets be consumed?
A
- Swallowed whole
- Chewed
- Dissolved in water (effervescent)
23
Q
How can tablets be consumed?
A
- Swallowed whole
- Chewed
- Dissolved in water (effervescent)
24
Q
What is reduced due to compaction process in tablets?
A
Surface area
25
What exipients can be added to tablets?
Disintegrants, wetting agents, binders
26
How is Bioavailability negatively impacted in tablets?
Tablet does not disintegrate rapidly for dissolution and absorption
27
What are the functions of a coated tablet?
- Aesthetics
- Mask an unpleasant taste
- Protect the tablet (environmental decomposition)
- Protect health workers from the drug
28
What are the functions of a gastro-resistant tablet?
Designed to resist the low pH of the stomach and be dissolved in the higher pH of the small intestine.
- Protect drugs sensitive to low pH
- Protect the stomach from irritants (Ibuprofen)
- Delay or prolong therapeutic release
29
What are prodrugs?
Chemically modified version of the active drug that require transformation in vivo to release the pharmacologically active drug
30
What barriers does prodrugs help overcome?
- Low oral absorption
- Chemical instbaility
- Localised toxicity/irration
- Poor solubility
- Rapid metabolism
- Low brain concentration (BBB)
31
What does prodrug improve?
Drug targetig (e.g cancer drugs)
32
What are the advantages of Oral administration?
- Easy for patients to administer
- Preferred by patients
- Can be formulated for slow release or to protect the drug from enzymatic or acidic degradation
33
What are the disadvantages of Oral administration?
- Slow onset
- Irregular absorption possibilities
- Destruction of drug by GI Tract
- Unsuitable for uncooperative patients
34
What the 4 pentrations methods of the skin?
Intramusclar, subcutaneous, Intravenous, Intradermal
35
How is IV injections administered?
Directly into a vein, avoiding uncertainities of absorption
36
What are the advantages of IV injections?
- Provides control as to the dose and rate of delivery
- 100% bioavailability
- Can be used for drugs poorly absorbed or ineffective when administered via alternative routes
- Drug has immediate action
- Irritant can be delivered (slowly to avoid vasoconstriction)
- Can inject large volumes
37
What are the disadvantages of IV injections?
- Administered by a professional
- Requires specialised equipment (medical waste)
- Sterile technique
- Causes the patient pain of injection
- Oily substances can’t be injected
- Risk of infection or embolism
38
What is the function of Glycopeptide antibiotic in Vancomycin?
- Inhibits cell wall synthesis
- Effective against gram postive bacteria
39
What is Vancomycin?
A bacterial antibiotic used gaainst resistant strains of streptococcus and staphylococcus.
40
How is Vancomycin administered?
- Orally for a local effect
- IV infusion to treat against MRSA and VRSA
41
How is the the subcutaneous injection administered??
Into the subcutaneous area of the skin, inject into the loose connective and adipose tissue under the skin
42
Where does the subcutanous injection take place?
Abdomen, upper arm
43
How much is injected in Subcutaneous injection/implant?
0.1 - 1ml
44
What is the advantages of Subcutaneous injection?
A depot (reservoir of the drug) is obtained
- slow release weeks / months
45
What is the disadvantages of Subcutaneous injections?
- Small volumes – concentrated drug
- Drug must not be an irritant
46
Examples of drugs using subcutanous injection/implants?
Insulin (DIabetes), Goraselin (Prostate cancer)
47
What is Intramuscular injection?
Injection into a muscle
48
Where are intramuscular injections adminstered?
Buttocks, deltoid muscle, thighs
49
How much is adminstered in intramuscular injections?
VOlumes up to 10 mL
50
What are the advantages of Intramuscular injection?
- Mild irritants can be administered
- Larger volume than subcutaneous
51
What are the disadvantages of intramuscular injections?
- Isotonic solutions are required otherwise It can be painful
- Pain caused by injection into the muscle
52
What is intrathecal administration?
Injection of a drug into the subarachnoid space via a lumbar puncture needle
53
What is the use for a intrathecal administration?
- Specialised purposes to gain access to the CNS
- Cross the BBB
54
Advantages of Intrathecal administration
- Allows transport directly to the CNS normally protected by the BBB
- Can have an immediate action
55
Disadvantages of Intrathecal administration?
- Painful
- RIsk of infection and back problems
56
What are examples of medicine that require Intrathecal administration
Morphine, Baclofen and antibiotics (meningtits)
57
What is Epidural injection?
Injection into the epidural space (interdural space)
58
Where does the Epidural injection takes place
Below the first cervical vertebrae
59
Where does the Epidural injection takes place
Below the first cervical vertebrae
60
Why is the Epidural injection is used?
During childbirth to numb pain while patient remains concious
Example: Lidocaine (Childbirth)
61
What are the 4 main compartments that 50-70% of water is located that contributes to body weight?
- Extracellular
-Intracellular
- Transcellular
- Fat
62
What is the volume of distribution (Vd)?
The volume that would contain the total body content of the drug ( Q ) at a concentration equal to that present in the plasma Cp
63
What is the equation to volume of distribution?
Vd = Q/Cp
64
What does volume of distribution describe?
Describes the relative affinity of the compound for plasma/blood constituents and tissue constituents
65
What does a higher volume of distribution (Vd) indicate?
Greater amount of tissue distribution
66
What affects volume of distrubution?
- Lipid solubility (cell penetration results in higher Vd)
- Plasma protein binding reduces Vd
- Tissue binding increases Vd
67
Why are drugs confined to plasma in volume of distribution?
• 0.05 L/kg, low Vd
• Heparin, molecule too large to cross capillary wall, following repeated dosing equilibration occurs
68
Why are dugs confined to extracellular compartment in volume of distribution?
• 0.2 L/kg, ~ Vd for polar compounds, gentamycin, vecuronium.
• Cannot enter cells easily, or pass blood / brain barriers freely - low lipid solubility
69
What is the distribution through body water?
0.55 L/kg, ~ Vd and distribution of drugs that readily cross membranes, ethanol, phenytoin
70
Why can volume of distribution be higher than the total body water?
Partitioning into body fat binding outside the plasma compartment
71
What affects pattern of distribution?
- pH partition, permability through tissue barriers, binding
- Within compartments fat:water partition
72
What is the equation for [D] octanol / [D] water?
Log P = ([D] octanol / [D] water)
73
What form are durgs in in therapuetic concentration in plasma?
Bound form
74
What state are unbound drugs are in therapeutic concentrations?
Pharmacologically active
75
In plasma protein binding, what molecules influence drug distribution?
Albumin, acid-glycoprotein and beta-globulin
76
What type of binding takes part in plasma protein binding?
Reversible and non-specific
77
What are important to consider in plasma protein when giivng a combination of drugs?
- Highly protein bound drug A (phenytoin)
- Drug B (warfarin)
- Drug B can be stopped, prior to surgery, this causes more of Drug A to become protein bound, leading to a seizure, as less of drug A is available in the blood stream.
78
What are unexpected effects in plasma protein binding?
Surge or drop in concentration - leads to side effects or overdose
79
What molecule is absorbed via the Gl tract
Levodopa
80
What is Levodopa?
A prodrug
81
What is the process of Levodopa in the Gl tract?
Crosses the BBB via an amino acid trasnprot mechansim
- Then conversion to active dopamine in nevre terminals in the basal ganglia
82
What does Zidouvdine do?
Selective toxicity towards cells infected with HIV
83
What does Diaacetyl morphine (Heroin) do?
A prodrug that penetrates the blood, brain barrier, has a potential for abuse
84
What is liposome?
Produced by sonication of an aqueous suspension of phospholipids
85
What are the properties of Liposomes dependent on?
- Composition
- Surface charge
- Size
- Method of preparation
86
Hwo does bilayer component determine the rigitiy?
• unsaturated phosphatidylcholice - more permeable less stable liposomes
• saturated phospholipids with long acyl chains - rigid less permeable bilayer
87
What are multiamellar liposomes?
Several concentric bilayers separated by aqueous areas
88
What is unilamellar liposome?
One phospholipid bilayer around a central aqueous area
89
What are Liposomes recongised by?
Phagocytic cells
90
What is BBB?
Blood brain barrier
91
What does BBB do?
A protectiv mechanism maintaining a stable environment
92
What is the major component of BBB?
Tight junctions between capillary endothelial cells
93
What nutrients are able to pass the BBB?
- Nutrients (glucose amino acids)
- Fats, fatty acids, oxygen CO2
- Nicotine, alcohol and anaesthetics can effect the brain
94
What factors influence drugs crossing the BBB?
Size, flexibility, conformation, lipophilicity, charge, enzymatic stability, affinity for transport carriers, plasma protein binding
95
What molecules can pass the BBB?
Babituates (small lipid soluble molecules)
96
What do not have a fully formed BBB?
Newborns
97
What compromises a BBB?
Trauma, inflammation and infection
