Gastro retentive Flashcards
What is GRDDS
an approach to prolong gastric residence time,
targeting site-specific drug release in the upper gastrointestinal tract (GIT) for local or
systemic effects.
Remain in the gastric region for long periods and hence significantly prolong the gastric retention time (GRT) of drugs.
Advantages of Gastroretentive
-Reduces dosing frequency for drugs with short half-life, improving patient compliance.
-Provides targeted therapy for local treatments.
-Reduces fluctuations in drug concentration, reducing concentration-dependent side effects.
-Enhances bioavailability compared to conventional controlled release formulations.
Factors controlling gastric
retention of dosage forms 8
➢ Density of dosage forms
➢ Size and shape
➢ Food intake and its nature (generally prolong gastric retention)
➢ Gender (female>male)
➢ Posture (depend on the dosage form)
➢ Age (elderly>young)
➢ Concomitant drug administration (i.e. opiate, cisapride..)
➢ Disease state (i.e. hypothyroidism or hyperthyroidism..)
Types of drug Candidates for GRDD 4
-Acting locally in the stomach: Amoxicillin, sucralfate and clarithromycin
-Narrow absorption Window: Ranitidine, riboflavin, theophylline, levodopa, furosemide, ciprofloxacin
-Degraded in intestinal fluid: Captopril
-Poorly soluble in intestine: Diazepam and verapamil HCl
Drugs unsuitable for GRDDS 3
➢ Drugs that have solubility problems in stomach (e.g. phenytoin).
➢ Drugs which are irritant to gastric mucosa
➢ Drugs that are unstable in the acidic environment of the stomach (e.g. erythromycin).
Classification of GRDDS 5
- High density systems
- Low density systems
- Expandable systems
- Mucoadhesive systems
- Magnetic system
High density (sinking) systems
Addesh el density?
e.g. of heavy intert material
a density within the range of 2.4-2.8 g/cm³
Able to withstand the movements of gastric peristalsis
accomplished by incorporating heavy inert materials such as zinc oxide, titanium dioxide,
barium sulphate or iron powder
Low density (floating) system
bulk density?
Do they affect gastric emptying
How is the drug released
What are the two types of systems involved?
a bulk density less then
gastric fluids (1.004-1.01 g/cm³)
so remain buoyant in the stomach
without affecting gastric emptying rate
for a prolonged period
the drug is released slowly from the system
They are divided into:
A. Non-effervescent systems
B. Effervescent/gas generating systems
Non-Effervescent systems
fi kmn 2 types
Hydrodynamically Balance Systems
Inherent Low Density Systems
Hydrodynamically balanced systems
They attain a low density (less than
1g/cm3) by swelling in gastric fluids
maintains its integrity and low density for a
predetermined period of time.
drug is released by
controlled diffusion through the
polymeric gel barrier.
Hydrodynamically balanced systems most used polymer?
Hydroxypropyl methylcellulose (HPMC)
Inherent low density systems
What are e.g. of low density material?
What is the advantage?
Floating is achieved by incorporation of low-density
materials, such as fatty substances, foam powder
(polypropylene), or by formulating porous and hollow systems.
provide immediate floating, thereby preventing the
risk of premature gastric emptying. (advabntagw)
Review el images bl lecture
Effervescent/gas generating systems: 2 types
Inflatable floating systems
Effervescent systems
Inflatable floating systems
Consists of shu? containg shu? which produces shu?
consist of inflatable chamber containing
volatile liquids which produce
gas at body temperature,
thereby initiating floating.
Inflatable floating systems image
Capsule = gelatin
Bioerodible polymer film = polylactic, polyanhydride
Inflatable chamber = organic liquid (ether) becomes gas at body temp
Drug reservoir is found on surface of chamber
Effervescent systems
Generate shu?
What kind of release?
E.g. of CO2 generating agents
generate CO2 gas, thereby reducing their density
enabling floating in the stomach with a sustained drug release.
utilize CO2 gas generating agents (e.g.
sodium bicarbonate with citric acid, tartaric acid or stomach acid) to achieve floatability
How to trap CO2
using swellable polymer (hydrocolloid) usually highly viscous not released easily
Gas impermeable polymer Eudragit RL will entrap gas + slow diffusion of water and frug
Expandable systems
small prior to oral intake, but expand later on in the stomach to a size larger than that of pyloric sphincter.
➢ These systems are classified into:
A. Swellable systems
B. Unfolding systems
Swellable systems
Are combined with polymer superdisintegrant sodium crosschalmodare?
Forms channels and allows water absorption
Facilitates expansion and swelling
Unfolding system
Disk unfolds containg drug in a gelatin capsule
Mucoadhesive systems
increases gastric residence time, thereby improving bioavailability.
Mucoadhesive polymers (chitosan, Carbopol, polyethylene oxide..) are characterized by their flexibility, hydrophilicity and biocompatibility.
Their hydrophilic functional groups are the hydroxyl and carboxylic that forms hydrogen bonding with mucin.
Attached on mucus membrane
Mucoadhesive polymers e.g.
(chitosan, Carbopol, polyethylene oxide..)
Magnetic systems
contains a small internal magnet, and an external magnet is placed on the abdomen
external magnet must be positioned with a degree of precision that might compromise patient
compliance
Metformin HCl®
Cifran OD® (Ciprofloxacine)
Effervescent floating system Products
Gabapentin GR®
Swelling technology Product
Madopar® (Levodopa and Benserzide)
Valrelease® (Diazepam)
Floating controlled release
capsule
Cytotec® (Misoprostol)
Bilayer floating capsule
Liquid gaviscon® (Alginic acid and sodium bicarbonate)
Topalkan® (Aluminium
magnesium antacid)
Effervescent floating liquid
alginate preparation
Evaluation of GRDDS
- Floating/buoyancy test
- Floating force
- Density
- Weight gain and water uptake
- Mucoadhesive properties
Floating/buoyancy test
Measures what?
Where is it stimulated?
What does float lag time mean?
What is the total floating period called?
- Measures the time taken by the dosage form to float on the surface of medium and the total floating period.
-performed in simulated gastric fluid that is
maintained at 37 °C.
- floating lag time :The time taken for the floating system to emerge on the surface of the medium
-the total floating period is called floating duration
-measures at each 30 sec
interval the vertical force (resultant
weight) required to keep the object
afloat on the surface of gastric fluids.
Density
How is it determined?
With what method can we measure density aslo?
Using what?
can be determined by geometric approach, where the volume (V) of dosage form having a known mass (M) is determined geometrically in order to calculate its density.
can also be measured by displacement method,
either by using pycnometer with organic solvent as a displacing liquid
Weight gain and water uptake
Awl shi dose is immersed in fluid
Then how is weight gain measured
What is the %swelling
The dosage form is usually immersed in simulated gastric fluids
at 37°C and the weight gain (water uptake) is measured at
regular time intervals
% swelling =
W𝑡−Wo
Wo × 100,
where Wt is the weight at time t and Wo is the original weigh
Mucoadhesive properties
How is it determined?
the artificial membrane is made of what
biological is made of what
determined by measuring the force required to separate the system from an artificial or biological membrane.
The artificial membrane can be cellophane,
the biological membrane can be rabbit stomach tissue.
The measurement can be done using a modified precision balance or a texture analyzer.
