Advanced drug delivery: Oral route Flashcards
(33 cards)
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)
