RATE CONTROLLED DRUG DELIVERY SYSTEM – ACTIVATION MODULATED

PRESENTED BY, MEENU

GEORGE

1

Rate controlled drug delivery system

The terminologies associated with novel DDS are sustained release controlled release

Sustained release describes a dosage form formulated to retard the release of a therapeutic agent such that its appearance in the systemic circulation is delayed or prolonged and its plasma profile is sustained in duration.

Controlled release implies a predictability and reproducibility in the drug release kinetics.

2

CLASSIFICATION1) Rate pre-programmed drug delivery systems2) Activation-modulated drug delivery systems3) Feed back-regulated drug delivery systems4) Site-targeting drug delivery systems

ACTIVATION MODULATED DDS:

Release of drug from the delivery systems is activated by some physical, chemical, or biochemical processes and facilitated by the energy supplied externally. The rate of drug release is then controlled by regulating the process applied or energy input. Based on the nature of the process applied or the type of energy used, these activation modulated DDS can be classified into,

3

Activation modulated1. Physical means a) Osmotic pressure-activated DDS b) Hydrodynamic pressure-activated DDS c) Vapour pressure-activated DDS d) Mechanically activated DDS e) Magnetically activated DDS f) Sonophoresis-activated DDS g) Iontophoresis-activated DDS h) Hydration-activated DDS2. Chemical means a) PH activated DDS b) Ion activated DDS c) Hydrolysis activated DDS3. Biochemical means a) Enzyme activated DDS b) Biochemical activated DDS

4

a) Osmotic pressure activated DDS

Depends on osmotic pressure to activate the drug release. The drug reservoir is contained within a semipermeable housing with controlled water permeability. The drug is activated to release in solution form at a constant rate through a delivery orifice. The rate of drug release is modulated by controlling the osmotic pressure gradient.

The drug release is activated by osmotic pressure and controlled at a rate determined by the water permeability and the effective surface area of the semipermeable housing as well as the osmotic pressure gradient.

5

Osmotic pressure activated DDS

Ex: Alzet osmotic pump. Drug reservoir is contained within a collapsible, impermeable bag whose external surface is coated with osmotically active salt. This reservoir is sealed inside a rigid semipermeable membrane. Water in the tissue fluid penetrate through the semipermeable housing and dissolve the osmotically active salt. This creates an osmotic pressure in the spacing between the reservoir compartment wall and the semipermeable housing. Due to this reservoir compartment is forced to reduce its volume and the drug solution is delivered at a controlled rate.

6

Alzet osmotic pump

7

b) Hydrodynamic pressure activated DDS

It is enclosed with a collapsible, impermeable container, which contains a liquid drug formulation, inside a rigid housing. A composite laminate of an absorbent and a swellable, hydrophilic polymer is sandwiched between the drug reservoir compartment and the housing. Laminate absorbs the GI fluid through the openings at the lower end of the housing and becomes swollen, which generates hydrodynamic pressure. This pressure forces the drug reservoir to reduce in volume and causes the drug formulation to release through the delivery orifice. The release of drug is activated by hydrodynamic pressure and controlled at a rate determined by the fluid permeability and effective surface area of the wall with annular openings as well as by the hydrodynamic pressure gradient.

8

Hydrodynamic pressure activated DDS

9

c) Vapour pressure activated DDS:

Drug reservoir in solution formulation, is contained inside the infusion compartment. It is separated from the pumping compartment by a partition. The pumping compartment contains a fluorocarbon fluid that vaporizes at body temperature and creates a vapour pressure. Due to this, the partition moves upward. This forces the drug solution to be delivered through flow regulators and delivery cannula into the blood circulation. The drug release is activated by vapour pressure and controlled at a rate determined by differential vapour pressure, formulation viscosity and size of the delivery cannula.

Examples: Implantable infusion pump for the constant infusion of,

heparin in anticoagulation treatment(Infusaid), insulin in antidiabetic medication, morphine for patients suffering from intense pain of terminal

cancer.10

Infusaid

d) Mechanically Activated DDS:

Drug reservoir is a solution formulation retained in a container equipped with a mechanically activated pumping system.

A measured dose of drug formulation is reproducibly delivered into a body cavity through the spray head upon manual activation of drug delivery pumping system.

The volume of solution delivered is controllable, as small as 10-100µl.

Example: Metered dose nebulizer for the intranasal

administration of buserelin, a synthetic analog of luteinizing hormone releasing hormone (LHRH) and insulin.

12

Mechanically Activated DDS:

13

e) Magnetically Activated DDS

Drug reservoir is a dispersion of peptide or protein powders in a polymer matrix from which macromolecular drug can be delivered only at a slow rate.

This low rate can be improved by incorporating an electromagnetically triggered vibration mechanism into the polymeric delivery device.

Here a tiny magnet ring is placed in the core of a hemispherical drug-dispersing polymer matrix. Then its external surface is coated with a drug-impermeable polymer, except one cavity at the centre of the flat surface. This uncoated cavity is positioned directly above the magnetic ring, which permits a peptide drug to be released.

14

Magnetically Activated DDS

15

f) Sonophoresis Activated DDS

Utilizes ultrasonic energy to activate the delivery of drugs from a polymeric drug delivery device.

The system can be fabricated from either a nondegradable polymer or a bio erodible polymer.

16

Sonophoresis Activated DDS

17

g) Iontophoresis Activated DDS:

Uses electrical current to activate and to modulate the diffusion of a charged drug molecule across a biological membrane, like skin.

Example: An Iontophoretic drug delivery system, Phoresor, facilitate the percutaneous penetration of anti-inflammatory drugs to surface tissues.Transdermal periodic iontotherapeutic system (TPIS), for the transdermal controlled delivery of insulin, in the control of hyperglycemia in diabetic animals.

18

TPIS

Phoresor

20

h) Hydration Activated DDS

Depends on the hydration-induced swelling process to activate the drug release. Drug reservoir is dispersed in a swellable polymer matrix fabricated from a hydrophilic polymer. The drug release is controlled by the rate of swelling of the polymer matrix. E.g.: Valrelease tablet.

It is prepared by a simple granulation process of homogeneous dispersion of Valium in hydrocolloid and pharmaceutical excipients. The granules are then compressed to form a compressed tablet. After oral intake the hydrocolloid in the tablet absorbs gastric fluid and forms a colloidal gel that starts from the tablet surface and grows inward. The release of Valium molecules is then controlled by matrix diffusion through this gel barrier.

21

Valrelease tablet

22

i) PH Activated DDS: This system permits targetting the delivery of a drug only in the region with a selected pH range.

It is fabricated by coating the drug-containing core with a PH sensitive polymer combination.

A gastric fluid-labile drug is protected by encapsulating it inside a polymer membrane that resists the degradative action of gastric pH.

E.g.: combination of ethyl cellulose and hydroxyl methylcellulose phthalate.

 

23

24

j) Ion Activated DDS An ionic or a charged drug can be delivered. Prepared by first complexing an ionic drug with an ion-exchange resin containing a counter ion. The granules of drug-resin complex are first treated with an impregnating agent to reduce the rate of swelling in an aqueous environment. It is then coated by air suspension coating, with a water insoluble but water-permeable polymeric membrane. This membrane serves as a rate-controlling barrier to modulate the influx of ions as well as the release of drug. In an electrolyte medium, such as gastric fluid, ions diffuse into the system, react with the drug-resin complex, and trigger the release of ionic drug. Example: Pennkinetic – permits the formulation of liquid suspension dosage forms with sustained drug release properties for oral administration.

25

Ion Activated DDS

26

k) Hydrolysis Activated DDS

Depends on the hydrolysis process to activate the drug release. Drug reservoir is either encapsulated in microcapsules or dispersed in microspheres or nanoparticles for injection. It can also be fabricated as an implantable device. All these systems are prepared from a bio-erodible or biodegradable polymer. The release of drug from the polymer matrix is activated by the hydrolysis-induced degradation of polymer chains and controlled by the rate of polymer degradation.

Ex: LHRH releasing biodegradable subdermal implant, which deliver goserelin, a synthetic LHRH analog, for the treatment of prostate carcinoma.

27

Hydrolysis Activated DDS

l) Enzyme Activated DDS

Depends on the enzymatic process to activate the drug release.

Drug reservoir is either physically entrapped in microspheres or chemically bound to polymer chains from biopolymers, such as albumins or polypeptides.

The release of drug is activated by the enzymatic hydrolysis of the biopolymers by a specific enzyme in the target tissue.

Ex: Albumin microspheres that release 5-fluorouracil by protease-activated biodegradation.

29

Enzyme Activated DDS

30

References1. Novel drug delivery system – Yie W Chien.2. www.google.com

31

Thank you

32