Advanced drug delivery: Oral route Flashcards
what are the aims of new technology in oral drug delivery?
Deliver drug at peak time
Deliver in the part of the GI they are best absorbed at
Deliver continuously along the GI
which organs are most of the drugs absorbed in
Duodenum
Jejunum 1
Portal vein tract
what are the physiological factors that affect oral bioavailability?
Transit time pH Microflora Enzymes Redox potential Presence of solids and liquids
what does the transit time of a drug correspond to?
The amount of time the drug is in contact with the mucosa for absorption.
What are the transit times in the stomach, SI, and colon?
SI = 3-5 hrs Colon =8-15 hrs - longer due to movements that happen (retrograde) The stomach: extremely variable *30min d<2mm and liquids *3h d>7mm, up to 10h with heavy meal
What factors affect transit time
size density dietary intake (fat) posture- sitting/ lying down/very mobile gender age exercise emotional state stress disease
What type of contractions and movement occur in the colon?
Retrograde contractions: retaining and mixing luminal content for prolonged time
Annular contractions: Divide up faecal mass
Segmenting movements
Propulsive movements
What are the pH’s along the stomach, SI and Large intestine ?
both fasted and fed
Stomach: -Fasted: 1.5-3 -Fed: 2-5 SI: -Fasted: 6.1 -Fed: 5.4 -Ileum:7-8 Large intestine -Caecum and colon: 5.5-7 -Rectum:7
What are the count of bacteria along the Gi tract
Saliva: 10^7 (aerobes + anaerobes)
Stomach:10^4-10^8 fed; ~ 0 fasted
Small intestine: Duodenum:10^3-10^4 (peristalsis and bile)
Colon: 10^11, only anaerobes
Which enzymes are found in which part of the GI tract?
Small intestine:
>Pancreatic secretions- Esterases, lipases, amylases, proteases, nucleases
>Brush border- Glycosidases, disaccharidases
Colon: specific enzymes that breaks down which have been broken down before
> Di-tri-saccharidases, mucoplysaccharidases, b-gucuronidases, b-xylosidases, a-arabinosidases, b-glucosidases, nitroreductases, azoreductases, deaminases, hydroxylases
What is the redox potential in the SI and colon?
SI: -69±90 mV
Colon: -415±72 mV
HoW does the presence of food and liquids affect the drug delivery?
- It delays gastric emptying
- Drug binding and complexation (tetracyclines + Ca2+ from dairy products)
- Splanchnic (internal organ) blood flow increased reduced 1st pass metabolism
- The amount of liquid present in the lumen decreases along the GIT and it is minimum in the colon
How does the presence of food and liquids affect the drug delivery?
- It delays gastric emptying
- Drug binding and complexation (tetracyclines + Ca2+ from dairy products)
- Splanchnic (internal organ) blood flow increased reduced 1st pass metabolism
- The amount of liquid present in the lumen decreases along the GIT and it is minimum in the colon
What are the advantage of oral drug delivery route
> Convenience and compliance
Large surface area for drug absorption
Rich blood supply for distribution
Peristaltic movement in the stomach is good for mixing
Prolonged retention
Different types of formulations available
What are the disadvantage of oral rug delivery route?
There is variability along the GI tract ADRs can occur High enzyme activity 1st pass metabolism Extreme pH and pH changes
What current technologies are available for oral delivery?
> Conventional dosage forms: tablets, capsules, supensions, emulsions, solution, etc.
> Prodrugs
> Advanced tablet formulations
> Advanced pellet formulations
> Advanced capsule formulations
> pH responsive formulations
what are Pro-drugs and their purpose
They are compounds resulting from the modification of a biologically active compound.
prepared in order to:
> increase absorption (adding lipophilic moieties)
> protect from enzymatic degradation
> avoid premature absorption (colonic delivery)
List the types of advanced tablet formulations?
- Osmotic tablets
- Gellable barrier layers
- Erodible barrier layers
- Tablet rupture
Describe the structure and the way osmotic tablet work.
They have a core and a semi-permeable membrane
Water from stomach enters through the membrane to the core.
The drug dissolved and pumps out through the exit orifice.
Osmotic agents: NaCl, hydrophilic polymers
How do the push-pull osmotic system work
Has Capsule shape with layers >2-laser-drilled deliver orifice >Drug compartment 1 >Drug compartment 2 >Polymer push compartment
Water is absorbed into the polymer layer and swells.
This pushes the drug out of the orifice layer.
Describe the gellable barrier layer mechanism work.
It is when the gell layer around a tablet absorbs water, and the drug diffuses through the gullible barrier
Delayed release occur and a sustained release after the lag
How does the erodiable barrier layer work
The outer layer absorbs water and is eroded to release the drug.
The drug profile is very step and doesn’t last long
What will combined system of swellable-erodabile work
Layer 1: is a burst release
Layer 2: Layer will absorp water and either erode or swell.
Then the other half or 2nd drug is released
How do tablets that erode work
The table core contains a disintegrant
Work by osmotic agent to absorb water till there is high internal pressure.
The coating raptures and the drug is release
Normally coated in ethylcellulose (diffusion arrive ) and eusragit (increase solubility and permeability along GI due to pH)
How to tablets that rupture works
tablet core contains a disintegrate
osmotic agent absorbing water
internal pressure is too high the coating ruptures releasing the drug
Coated in:
Ethylcellulose: diffusion burrier to retard release
How to advanced capsule formulations work
Hydrogel composition and wall thickness control water diffusion and delays drug release
Swelling agent absorbs water and pushed the plug out releasing the drug
How do advanced pellet formulations work
Loaded into a capsule and releases small pellets
-different types of pellets can be placed in on tablet
Provide sigmoidal shape
-mixture of matrix and revivor
Membrane made by:
>Ethylcellulose
and
>Eudragit: etheric coating
increases solubility and permeability as it transits along the GIT tract due to increase in pH giving an increasing rate of drug release
-This will cause pore to evolve very slowly with increase in solubility of Eudragit
How do pH responsive formulations work
pH polymer used: change in solubility
Eudargit based on (METH)ACRYLATES
- Modifiable to different pH sensitivity
- R group changes
What are the different R groups of Methacrylate and what are the affects
Methyl co-polymer: Anionic: Gastro resistant
Types of colon targeting
pH-controlled systems
Time-controlled systems
Pressure-controlled systems
Enzyme-controlled systems
pH controlled colon targeting
Eudragit soluble at pH 6 or 7 can be used for enteric coating of colon targeted systems
pH =7.5 in the small intestine can cause early release of drug
Eudragit soluble at pH 7.5 and slowly swelling can be used: in vivo some dosage froms were found not to break down at all
Intra- and inter-individual changes in pH make this systems not reliable
time controlled colon targeting
Times
-Stomach - 30 mins or 3hrs
SI: 3-5 hrs
Colon:8-15 hrs
Pressure controlled colon targeting
Muscular contractions in the gastrointestinal tract generate an internal pressure that varies depending on the location
High pressure in the fed stomach could lead to premature drug release
Ethylcellulose capsules of different size and thickness
