Oral Dosage Forms Flashcards by Becky Neil

How do small lipophilic compounds permeate?

Paracellular water channels

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How do lipophilic compounds permeate?

Transcellular Route

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Are Class I drugs eligible for a Biowaiver?

Yes

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Are Class II drugs eligible for a Biowaiver?

If weak acids, highly souble at pH6.8 pluss dissolution

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Are Class III drugs eligible for a Biowaiver?

If very rapidly dissolving

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Are Class IV drugs eligible for a Biowaiver?

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When are drugs considered highly soluble?

Highest dose dissolves in <250ml water over pH 1-7.5

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When are drugs considered highly permeable?

If >90% of the dose is absorbed

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What solubility impairs solubilisation during formulation?

<10mg/ml

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What form are BSC class I more clinically effective in?

Immediate release or controlled release

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What effects does a low solubility have in vivo?

Decreased bioavailability
Suboptimal
Increased chance of food effects
Increased issues in patients with diseases - esp GIT problems relating to blood flow
More frequent incomplete release of drug
Higher inter-patient variability
Inability to optimise lead compounds
Harsh excipients required
Extreme basic or acidic conditions needed
Uncontrollable precipitation after dosing
Non-compliance due to dosing

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Which factors affect solubility and permeability?

Wettability
Surfactants
Particle size
Solid dispersions
Polymorphs
pH solubility
Soluble prodrugs
Complexation
Adsorbents
Viscosity
Degredation
Diluents

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How can permeation be enhanced?

Absorption enhancing excipients
Efflux inhibitors
Lipid filled capsules
GI motility consideration

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How can solubility be enhanced?

Particle size reduction
Soluble salts
Solid dispersions
Self-emusifying systems
Surfactants
Nanoparticles
Cyclodextrin
pH diffusion layer

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How can both solubility and permeability of a drug be enhanced?

Prodrugs
Salt forms
CO-solevents
Solubilisation by surfactants
Lipid-filled capsules
Nonparticles
Liposomes
Lyophilisation

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What is the structure of Cyclodextrins?

Hydrophobic interior
Hydrophilic exterior
Form complexes with hydrophobic compounds

How are CD’s formed?

Supersaturating a CD solution with a drug and agitate

Kneading a drug/CD.solvent slurry to paste which is dried and sieved

How can CD solubilising effect be improved?

Hydrophilic polymers (HPMC) so less CD needed for same amount of drug

What is the disadvantages of CD’s?

Toxicity and stability issues

What is the disadvantages of amorphous solid dispersions?

Unstable

Prone to recrystallisation

How are amorphous compounds created?

Formulation with polymers
Spray dry using solvents or supercritical fluids
OR
Hot melt extrusion (soften polymer, add drug, mix as it flows through extruder. rapidly cool)

Describe PEG as a Polar excipient

Can be used as a co-solvent in liquid-based formulations - prevent precipitation
Topical and parenteral admin
Acts as a wetting agent/enhances dispersion
Incorporated by solvent evaporation/freeze drying
Can combine with other excipients

Describe Gelatin as a polar excipient

Both positive and negative charges

Used to improve the wettability of hydrophobic compounds when used as a granulating agent

Describe Sugar glasses as a polar excipient

Parenteral and pulmonary use, GRAS for oral
Inulin + drug + freeze dry = sugar glass
Improves dissolution profile and stability
Used in the formulation of cyclosporin, diazepam, amoxicillin, bacitracin, tetrahydrocannabinol

Describe Lipids as a polar excipient

Used in self emulsifying systems (lymphatic delivery)

How does particle engineering improve solubility?

Reduce size = increased surface area Can used lipid or anti-solvents to recrystallise which reduces particle size Conventional communition and spray drying = mechanical stress

What are the benefits are nanoparticle formulations of drug delivery?

Greater bioavailability - higher Cmax, AUC Less variability with food AUC proportional to dose

How are nanoparticles created?

Micromilling with pysical and thermal stress = sub-microns Piston gap methods with hydrodynamic cavitation = microns Supercritical Fluids create by control of solubility using pressure and temperature in solvents such as CO2

What are Supercritical fluids used for?

To produce different sizes and shapes of drug particles

How do supercritical fluids work?

At a temperature above their thermodynamic critical points, they assume the properties of both a liquid and a gas

What size can SCF solubilised drug particles re-crystallise at?

5-2000nm

How are SCF's manipulated?

At near critical temperatures SCF's are highly compressible - moderate changes in pressure or temp can alter density, mass transport and solvating power - improving diffusivity and reducing viscosity and surface tension

What role do non-ionic surfactants have in self-emulsifying systems?

Improve drug solubilisation and prevent drugs from precipitating out of the micro-emulsion

What are Tweens and | Labrafil with high HLB used for in a self emulsifying systems?

Ensure immediate formulation of O/W droplets

What are ethanol/PEG/propylene glycol used for in a self emulsifying systems?

Increase the amount of drug dissolved in the lipid base

How are solid particles formulated into self emulsifying systems?

Suspension-dried | Produces a stable colloidal micro-emulsion suspension of sub-micron drug particles in a solid lipid matrix

What is a self emulsifying system used for?

Poorly soluble, lipophilic drugs

What does the presence of lipid in the duodenum stimulate?

Secretion of biliary lipids - generates colloidal micelles, mixed micelles and emulsion droplets