D7. Disintegration, disaggregation and dissolution Flashcards
Excipients to modify drug release from tablets?
-polymeric coating materials – eg enteric coating polymers (reminder)
-achieve delayed release of drug
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formulation for Asacol delayed-release tablet for oral administration?
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How do Hydrophilic swelling polymers as excipientswork?
-matrix swelling
-matrix/ gel erosion
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Describe matrix swelling in Hydrophilic swelling polymers as excipients
-surface hydrates and creates viscous gel structure
-gel is a barrier to liquid ingress into tablet and drug diffusion out. This stage important for release of water soluble drugs
Describe matrix/gel erosion in Hydrophilic swelling polymers as excipients
gradually gel matrix erodes in GI tract |this stage is important for release of water insoluble drugs
Examples of modified release formulations in BNF?
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What is dissolution?
dissolution is a process where solid dissolves at the solid-liquid interface, dissolved molecules diffuse to the bulk solution
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three models which either alone or in combination, used to describe the dissolution mechanisms:
-Diffusion layer model
-Interfacial Barrier Model
-Danckwert’s Model
Describe Diffusion layer modelNoyes-Whitney model
-assumes that a layer of liquid, H, adjacent to the solid surface remains stagnant
-the dissolution at the solid/liquid interface is assumed to be instantaneous forming a saturated solution, Cs, of the solid in the static liquid film
-relevant for water soluble drugs
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Describe Noyes-Whitney equation
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Factors affecting drug dissolution rate?
-temperature – affects solubility (Cs) and diffusion (D)
often you warm up to dissolve
-agitation – affects static layer (h)
stirring of medium (stirring sugar into tea)
-viscosity – affects diffusion (D)
-wettability – affects area for drug release (A)
eg. hydrophobic lubricant reduces wettability and hence surface area for release
-pH – affects drug solubility (Cs) –
when drug has pH dependent solubility (weak acid and bases)
-particle size - affects surface area (A)
decreasing particles size -> improves dissolution and bioavailability of drug with poor solubility
(poor solubility < 0.05 g/l)
-polymorphic form
different crystal structures of the same drug => different solubility => Cs is affected; particularly important for poorly soluble drugs
Describe Interfacial barrier model
-assumed that the process at the solid/liquid interface is not instantaneous due to a high activation free energy barrier which has to be surmounted before the solid can dissolve.
-once the barrier is overcome, the dissolution mechanism is essentially the same as in diffusion layer model
-relevant to poorly soluble drugs
-the rate of diffusion in the static layer is relatively fast in comparison with the surmounting of the energy barrier, which therefore becomes rate limiting in the dissolution process
-Increased complexity of model and equation
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Describe Danckwert’s model
-The Danckwert’s model (from ~ the1950) assumes that packets of solvent reach the solid/liquid interface by diffusion in some random fashion.
-at the interface, the packet of water is able to absorb solute (solid material that is dissolving) according to the laws of diffusion and is then replaced by a new packet of solvent.
-this surface renewal process is related to the solute transport rate and hence to the dissolution rate
-Increased complexity of model and equation
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Tabletting excipients to aid disintegration and dissolution?
-wetting agents in tablet formulation promote surface interaction with water and water penetration into tablet - enhancing disintegration
-an interracially adsorbing agent (surfactant) can improve the dissolution rate by changing surface properties of drug particles
Uniformity of weight?
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Uniformity of content?
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Disintegration of tablet?
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Dissolution testing – ie. drug dissolution?
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Tablet hardness / breaking strength / resistance to crushing testing?
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Resistance to abrasion – Friability testing
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Fast Dissolving Oral Delivery Formulations?
-solid dosage form that dissolves or disintegrates rapidly in oral cavity, resulting in solution or suspension without the need of water
-synonyms: Orodispersable tablets, melts
drug from the formulation dissolves or disperses in the saliva…
for some drugs a portion may be absorbed from the mouth, pharynx and oesophagus as the saliva passes towards the stomach (potentially increased absorption/bioavailability)
fast dissolution of formulation in the mouth is achieved…
-formulations are either very porous or soft moulded matrices or compressed into tablets with very low compression force
-often require specialized ‘peel-off blister’ packaging)
Targeting Drugs to the Colon: Colon bacteria approach(gut microbiota role)?
-majority bacteria in GIT are present in the distal gut
-colonic bacteria predominantly anaerobic
-secrete enzymes capable of metabolizing endogenous and exogenous substances (carbohydrates, proteins) which escape digestion in the upper GI tract
-Consequence: materials that are susceptible to bacterial fermentation in the colon (while remaining stable in the stomach and small intestine) could be utilized to target drug delivery to the colon
Improving drug bioavailability by gastro-retention; gastroretentive strategies?
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