1
Q
Traditionally how is paediatric dosing calculated?
A
Weight based (mg/kg)
2
Q
Formulation determines what dose can…
A
Successfully be delivered to the paediatric patient
3
Q
Who are potential paediatrics?
A
New-borns, infants, toddlers, young children, and adolescents
4
Q
Feeding:
4-5 months
7 months
A
- Children put everything in their mouths to push back gag response to start solid foods
- Introduce lumpy puree and solid textures
5
Q
Risk factors for paediatric treatment
A
- Different/changing pharmacokinetic parameters, difficulty with administration routes
- Lack of paediatric formulations (dosage forms)
- Oversight of pharmacy calculation errors
- Incorrect measurement of preparations
6
Q
Which discharges quicker from the stomach: liquids or solids?
When does this process particularly happen?
A
- Liquids
- The dimensions of particles can pass through the pylorus can limit gastric emptying
7
Q
Practical issues in paediatric drug dosing
A
- Complex solid dosage forms do not consider paediatric GI physiology
- Palatability is the major issue with compliance with oral liquids and chewable tablets
- Dosing of children usually depends on parent/guardian
8
Q
Paediatric formulation approaches:
Bona fide (proprietary) examples
Extemporaneous paediatric formulations
A
- Drops, suspensions, chewable tablets, or syrups
- Made with “standardised” extemporaneous vehicles (BNF, BP, or marketed vehicles)
- With food (sprinkles on apple sauce or yoghurt)
- Made with “standardised” extemporaneous vehicles (BNF, BP, or marketed vehicles)
9
Q
Paediatric dosage forms - oral:
A
Solutions, suspensions, elixirs, syrups, drops, granules, sprinkle oral powder, powders for reconstitution as suspension, tablets/minitablets, dispersible tablets/orally, disintegrating tablets, effervescent tablets, chewable tablets, capsules
10
Q
Paediatric dosage forms - rectal:
A
Suppositories, solutions, foams
11
Q
Paediatric dosage forms - cutaneous:
A
Creams
Ointments
12
Q
Paediatric dosage forms - percutaneous:
A
Patches
13
Q
Paediatric dosage forms - intravenous:
A
Solutions
Emulsions
14
Q
Determinant drug forms for children
A
- Age
- Ability to swallow solid dosage forms
- Disease/disorder being treated
15
Q
Challenges for formulation and dispensing
A
- Dose accuracy
- Route of administration
- Patient compliance
- Choice of excipients (toxicity and safety)
- Physical and chemical properties of drug
16
Q
General considerations in paediatric dosing:
Children under 2 years
Ages 2-6 years
Over the age of 6
Most children 12 years and older
A
- Liquid dosage forms widely accepted
- Ability of a child to swallow a small tablet/capsule is variable
- Better acceptance of small to medium tablets intended for swallowing, significant % still unable to swallow
- Can swallow a tablet of reasonable size, varies from patient to patient
17
Q
General considerations in paediatric dosing:
What dosage form is most flexible in paediatrics?
What are the limitations of this dosage form?
A
- Liquid forms
- Need shaking before use otherwise will have unequal drug delivery
- Often have palatable issues with both texture and flavour
- Transport large multi-use bottles
- Accurate measuring
- Volume must be taken into consideration
- Liquids require preservatives which produce toxicity/safety concerns
- Main challenge is taste masking which is costly and may not be achievable
18
Q
Extemporaneous formulations:
Limitations
A
- Lack of commercially available preparations
- Lack of dose accuracy
- Bioavailability
- Stability
- Consistency and uniformity
- Effect of food
- Interactions with other drugs/food or herbal treatments
19
Q
Extemporaneous formulations - manipulating adult forms:
Crushing
Splitting
Part volume
A
- Crush tablet / open capsule and add dosing vehicle to prepare liquid preparation
- Crush tablet / open capsule and add soft food
- Crush tablet / open capsule and add dosing vehicle to prepare liquid preparation
- Split tablet into segments to enable swallowability and appropriate dose strength
- Use only part of the volume of the parenteral preparation to have lower dose
20
Q
Dispensing devices examples
A
- Measuring spoons
- Graduated measuring cups
- Oral dosage syringes
- Pill swallowing cup
- Modified feeding bottle
21
Q
When prescribing drugs to children you should…
Assign…
Conduct…
Consider…
Consider…
A
- intended dose according to weight and age
- preliminary test of tolerance and sensitivity to drugs
- functional state of vital organs
- the dosage form and dispensing
22
Q
Semi solids and medicines for children - semi solid dosage forms:
Examples
What do semi solid dosage forms rely on?
A
- Syrups, suspensions, cream. ointments, gels, aerosols
- The Phase Diagram Oil-water-surfactants
23
Q
Semi solid dosage forms:
What is the hydrophilic-lipophilic balance scale based on?
A
Surface tension and a surfactants value indicates what role it has when formulating semi solids
24
Q
What does pharmaceutics mean?
A
The science of pharmaceutical (drug-related) systems, focusing on the physiological and chemical factors controlling drug disposition relevant to therapeutic action
25
Pharmaceutics - biopharmaceutical considerations:
Examples
Factors affecting absorption of drug from different formulations with diff. administration routes
26
Pharmaceutics - therapeutic considerations:
Examples
Disease to be treated, rapidity of onset drug action desired
27
Pharmaceutics - drug factors:
Examples
Physical and chemical properties of drug substance such as solubility, stability
28
What does pharmaceutics cover?
Physical chemistry
Physical organic chemistry
Mathematics
Bioengineering
Nanotechnology
29
Diffusion:
What is flux across interface?
What is the flux from diffusion process defined as?
1. No. molecules per unit area per unit time
2. Ficks' Law
30
What is the equation of steady-state diffusion?
Flux proportional to conc. gradient
31
Equation of Fick's first law of diffusion
J = -D (dC/dx)
D = diffusion coefficient
32
For drugs with rapid onset of action (seconds), how can we administer?
For onset of action between minutes and hours, how can we administer?
For onset of action of up to days, how can we administer?
1. Injection, rapid relief use aerosols
2. Tablets
3. Depot injection or implant
33
Drug factors in dosage form design
- Physical and chemical properties of drug can affect dosage form choice
- Processing/manipulation into dosage form during manufacture can also affect efficacy
34
What properties of a drug should be considered?
Organoleptic properties (taste/look)
Solubility
Dissolution
Partition coefficient
Crystal properties (polymorphism)
Stability
35
Properties of drug - organoleptic properties (taste/look):
What needs to be considered?
What can be used?
1. Particle shape/size
2. Can use water insoluble derivatives, flavourings, perfumes, colourings
36
Properties of drugs - solubility:
All drugs must show...
Can reduce what?
What are pH dependent?
1. Some aqueous solubility to be therapeutically active
2. Particle size or complex with soluble agents
3. Acidic basic compound solubilities
37
Properties of drugs - solubility:
All drugs must show...
Can reduce what?
What are pH dependent?
1. Some aqueous solubility to be therapeutically active
2. Particle size or complex with soluble agents
3. Acidic basic compound solubilities
38
Properties of drugs - dissolution:
Process by which?
Drug dissolve
39
Properties of drugs - partition coefficient:
Gives measure of?
What can be calculated by Henderson-Hasselbach equation?
1. Measure of rate of transport across lipid membranes
2. Proportion of ionised to unionised species with pH
40
Properties of drugs - crystal properties (polymorphism):
What drugs are amorphous?
What is polymorphism?
What does a crystal arrangement mean?
1. Drugs with no crystalline lattice arrangement
2. Different arrangements of drug in crystal lattice
3. Affects solubility and melting point
41
Properties of drugs - stability:
Can be affected by?
May require use of?
1. Temperature, humidity, atmosphere, light
2. Antioxidants, moisture/light resistant packaging, buffers, antimicrobial preservatives
42
What are kinetics?
What arises from diffusion?
1. Role in describing fate of drug
2. Interface transport arises from diffusion
43
Factors contributing to overall colloidal system nature
1. Particle size, shape, flexibility
2. Surface properties (inc. electrical)
3. Particle-particle interactions
4. Particle-solvent interactions
5. Solvent-solvent interactions (important in aq. systems)
44
Classification of colloidal systems
1. Colloidal dispersions - thermodynamically unstable, irreversible after phase separation e.g. emulsions, creams and suspensions
2. Solutions of macromolecules - thermodynamically stable and reversible
3. Association colloids - thermodynamically stable aggregates of molecules in solution
45
Classification of products w/oil/water/surfactant to deliver
1. Rheology
2. Loss on drying (LOD), water and organic solvents
3. Specific gravity, density
4. Surface tension, component interaction
5. Thermogravimetric analysis (TGA)
6. Visible transmittance, optical appearance clear or turbid
7. Visual appearance and feel, in particular how spreads feel on application
8. Microscopic examination, gives indication of how components are mixed/dispersed
46
What is wax?
What does lipophilic mean?
What property is petroleum?
What property is paraffin?
1. Solid which is plastic at room temperature and has low viscosity liquid above melting point
2. Soluble in organic solvents and immiscible with water
3. Microcrystalline
4. Crystalline
47
What does amphipathic mean?
What does amphiphile mean?
1. A molecule having both hydrophilic and hydrophobic parts
2. A molecule that contains both a water loving polar part (hydrophilic) and a water hating non-polar part (hydrophobic)
48
What is surfactant?
What is zwitterionic
1. An amphiphilic substance which tends to reduce the surface tension of a liquid
2. A neutral molecule (net charge of zero) with a positive and a negative electrical charge. Multiple positive and negative charges can be present
49
What do amphiphilic molecules in aqueous solution tend to do?
What reduces surface tension?
1. Seek out the surface & orientate themselves to remove the hydrophobic group from the aqueous environment, achieving minimum free energy state
2. Forces of intermolecular attraction between water molecules and non-polar groups are less than two water molecules
50
What happens as the concentration of aqueous solutions increases?
When do micelles form?
What do the micelles then do and what interactions occur?
1. There is a pronounced change in the physical properties
2. As the concentration increases, at a critical concentration many amphiphilic molecules form aggregates in solution (micelles)
3. The micelles collide and coalesce into layers: all driven by hydration- solubility and inter molecular interactions
51
What is surface free energy?
If the surface of the liquid increases, the energy of the liquid also increases. This energy is proportional to the size of the free surface
52
Tensions:
Where does the value of interfacial tension at the liquid-liquid interface lie?
What is the magnitude of surface and interfacial tensions dependent on?
What molecule has a low surface tension?
1. The surface tensions of the two liquids, except when an interaction occurs
2. The intermolecular forces between molecules in the liquids
3. Alkanes, interact only via dispersion forces
53
Measurement of tensions:
What is the ring method based on?
How is the force mentioned measured?
1. The fact that the force necessary to detach a platinum-iridium ring immersed at the surface is proportional to the surface tension
2. Either by suspending the ring from the arm of a balance or by using a torsion-wire arrangement
54
Measurement of tensions:
What happens as the hydrocarbon chain is increased?
What is adsorbed at the surface and hence causes?
1. The balance between
[Alcohol]aq ←→ [Alcohol]surf shifts to the right
2. More alcohol molecules hence a greater reduction in surface tension
55
Measurement of tensions:
What leads to an increase in surface tension?
Since ion-water interactions are much stronger than water-water interactions, what occurs?
What lowers the interfacial tension between oil and water phases?
1. An increase in concentration of NaCl salt in aqueous solution
2. The ions do not approach the solution surface, ions are fully hydrated and remain in the bulk of the solution
3. The adsorption of surfactants at an interface lowers the interfacial tension and facilitates emulsion formation
56
Emulsions:
What are emulsions?
What do emulsion droplets exhibit?
How does the stabilisation occur?
1. Are liquid dispersions of two immiscible fluids, one being dispersed in the other, in the presence of surface active agents
2. All the classical behaviours of metastable colloids
3. Emulsifiers are surfactants and these surfactants concentrate at the interface
57
Emulsions:
What distribution is orientated due to hydrophobic interactions?
What does this process enable?
1. The distribution of surfactant across the interface between the two immiscible liquids
2. The surfactant to reduce the interfacial tension between immiscible liquids
58
Adsorbed film and interfacial tension theory;
Therodynamics equation
Suppose what solution?
What does emulsifying surfactant reduce?
1. ∆ G = γ ∆ A
2. 10% v/v oil in water
3. Interfacial tension
59
Oriented wedge theory:
How do the molecules of surfactant orient themselves?
What does this do?
What if the non-polar end of the molecule of the emulsifying agent is smaller?
1. In the interface between oil and water with the hydrocarbon radicle toward the oil, and the -COO- Na+ toward the water.
2. Thus the oil-like or non-polar end turns toward the oil, and the polar end toward the polar liquid
3. The emulsion will be one of oil in water- while if the polar end is the smaller, the droplets will be of water
60
Electrical double layer theory:
Larger the what, the greater the repulsion between what?
Larger is the ζ potential , greater is the repulsion between the droplets and better is the emulsion stability
61
Phase volume theory:
What maximises contact between particle and with the continuous phase?
The packing in a stable emulsion
62
Hydration theory:
What are the properties of hydrated water?
Different
Pharmacy 102
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