Bp801t notes Ndds unit 1 notes BP704T
Controlled drug delivery system and polymers
Introduction
Controlled drug delivery is one which delivers the drug at a predetermined rate, locally or
systemically, for a specified period of time.
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• Controlled release drug administration means not only prolongation of the duration of drug
delivery, similar to the objective in sustained release and prolonged release, but the term also
implies the predictability and reproducibility of drug release kinetics.
Some important terminology
Sustained release drug delivery:
Any of the dosage form that maintains the therapeutic blood or tissue
levels of drug by continuous release of medication for a prolonged period of time, after administration of
a single dose. In case of injectable dosage forms it may vary from days to months.
Bp801t biostatistics notes
https://pharmanote2.blogspot.com/2022/09/bp801t-biostatistics-notes.html
Site specific and receptor targeting:
Targeting a drug directly to a certain biological location .For site
specific release the target is the adjacent to or in the diseased organ or tissue, for receptor release the
target is the particular drug receptor within an organ or tissue.
Controlled release drug delivery:
Delivery of the drug at a predetermined rate and /or to a location
according to the needs of the body and disease states for a definite period of time.
APPROACHES TO DESIGN CONTROLLED RELEASE FORMULATIONS
1. Continuous release system / Dissolution controlled drug release system
a. Matrix dissolution controlled system
b. Encapsulation/coating dissolution controlled drug release system
2. Diffusion controlled drug release system
a. Matrix diffusion system
b. Reservoir devices
3. Dissolution and diffusion controlled drug release system
4. Ion exchange resin drug complexes
5. pH depending formulation
6. Osmotic pressure controlled system
7. Hydrodynamic pressure controlled system
1. DISSOLUTION CONTROLLED DRUG RELEASE SYSTEM
• Dissolution is defined as solid substance solubilised in a given solvent.
• It is a rate determining step when liquid is diffusing from solid.
• Several theories explain dissolution:
- Diffusion layer theory,
- Surface renewal theory,
- Limited solvation theory.
• Noyes Whitney Equation:
dc/dt = Dissolution rate of drug
k= Dissolution rate constant (1st order)
Cs = Saturation/ maximum drug solubility
C = Conc. of drug in bulk solution
Cs-C=concentration gradient
a. Matrix type:
• Also called as Monolithic dissolution controlled system since the drug homogenously dispersed
throughout a rate controlling medium waxes (beeswax, carnauba wax, hydrogenated castor oil
etc) which controls drug dissolution by:
1. Altering porosity of tablet.
2. Decreasing its wettebility.
3. Dissolving at slower rate.
• Exhibit First order drug release.
• Drug release determined by dissolution rate of polymer.
• Examples: Demeaned extencaps, Dimetapp extentabs.
b. Encapsulation type:
• Also called as Coating dissolution controlled system since the drug encapsulated, with slowly
dissolving material like cellulose, PEG, PMA (polymethylacrylates) & waxes.
• Dissolution rate of coat depends upon stability & thickness of coating.
• Examples: Ornade spansules, Chlortrimeto Repetabs.
2. DIFFUSION CONTROLLED DRUG RELEASE SYSTEM
• It is a major process for absorption in which no energy required.
• In this drug molecules diffuse from a region of higher concentration to lower concentration until
equilibrium is attained and it is directly proportional to the concentration gradient across the
membrane.
• In this system release rate is determined by its diffusion through a water-insoluble polymer.
a. Matrix diffusion system
• Rigid Matrix Diffusion: Materials used are insoluble plastics such as PVP & fatty acids.
• Swellable Matrix Diffusion: Also called as Glassy hydrogels. Popular for sustaining the release of
highly water soluble drugs. Materials used are hydrophilic gums.
Examples : Natural: Guar gum, Tragacanth.
Semi-synthetic: HPMC, CMC, Xantham gum.
Synthetic: Polyacrilamides.
• Drug and excipients are mixed with polymers such as Hydroxypropyl methylcellulose (HPMC) and
Hydroxypropyl cellulose (HPC).
• Tableted by conventional compression.
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• Release from the tablet takes place by combination of water diffuses into the tablet, swells the
polymer and dissolves the drug may diffuse out to be absorbed.
• Examples: Glucotrol XL, Procardia XL
• The Higuchi Equation describing the drug release from this system:
Reservoir System
• Also called as laminated matrix device.
• Hollow system containing an inner core surrounded in water insoluble membrane.
• Polymer can be applied by coating or microencapsulation.
• Rate controlling mechanism - partitioning into membrane with subsequent release into
surrounding fluid by diffusion.
• Commonly used polymers - HPC, ethyl cellulose & polyvinyl acetate.
• Examples: Nico-400, Nitro-Bid.
• Rate controlling steps: Polymeric content in coating, thickness of coating, hardness of
microcapsule.
3. DISSOLUTION & DIFFUSION CONTROLLED RELEASE SYSTEM
• Drug encased in a partially soluble membrane.
• Pores are created due to dissolution of parts of membrane.
• It permits entry of aqueous medium into core & drug dissolution.
• Diffusion of dissolved drug out of system.
• Ethyl cellulose & PVP mixture dissolves in water & creates pores of insoluble ethyl cellulose
membrane.
Bp704t notes
4. ION-EXCHANGE RESINS CONTROLLED RELEASE SYSTEMS
• Ion exchange resins are cross-linked water-insoluble polymers carrying ionizable functional
groups.
• Such system provides control release of an ionic (ionisable) drug.
• These resins are used for taste masking and controlled release system.
• The formulations are developed by embedding the drug molecules in the ion-exchange resin
matrix and this core is then coated with a semi permeable coating material such as Ethyl Cellulose.
• This system reduced the degradation of drug in GIT. H+ Clin the gastric fluid are exchange with
cationic and anionic drugs from the ion exchange resins.
Polymers
Polymers topic is not a most important you can skip that topic. Just read before exam only 2 marks question rare to see 10 or 7 marks question.
Application of cdds
The main advantages that polymeric drug delivery products can offer are;
1. Localized delivery of drug: The product can be implanted directly at the site where drug action is
needed and hence systemic exposure of the drug can be reduced. Especially for toxic drugs which are
related to various systemic side effects.
2. Sustained delivery of drug: The drug encapsulated is released over extended period and hence
eliminates the need for multiple injections. This feature can improve patient compliance especially for
drugs for chronic indications, requiring frequent injection.
3. Stabilization of the drug: The polymer can protect the drug from the physiological environment and
hence improve its stability in vivo. This feature makes this technology attractive for the delivery of labile
drugs like proteins.
4. On the other hand, natural polymers have the advantage of high biocompatibility and less
immunogenicity.
5. The composites of some of the natural polymers with synthetic polymers give added advantage as
carriers for drug delivery by complimenting the properties of each other.