Recent Advances in Colon Targeted Drug Delivery Systems

Presented by- Sulabh SinghaniaM.Pharm – 2nd SEM

DEPARTMENT OF PHARMACEUTICS

Enrollment No-201504100410019

05/01/2023 2

Novel Advancements in CDDSPCDCS.CODESTM.OROS – CT.Pulsincap system.Port system.Time clock system.Hydrophilic sandwich

capsule.

Chronotropic system.Colal – Pred system.Targit technology.Egalet technology.Enterion capsule

technology.

05/01/2023 3

Pressure-Controlled Drug-Delivery Systems(PCDDS)

• Lag time of 3-5 hrs is noted.• Driving force-Peristalsis.• Drug release occurs following disintegration of a water-

insoluble polymer capsule as a result of pressure.

• Thickness of the membrane, capsule size and density plays a crucial role in release.

• Drug delivered should be in liquid state to facilitate absorption as lumen content is already viscous.

05/01/2023 4

CODESTM

05/01/2023 5

CODESTM

• CODESTM is a combined approach of pH dependent and microbially triggered CDDS.

• The premise of the technology is that the enteric coating protects the tablet while it is located in the stomach and then dissolves quickly following gastric emptying.

• The acid soluble material coating then protects the preparation as it passes through the alkaline pH of the small intestine.

05/01/2023 6

CODESTM

• Once the tablet arrives in the colon, the bacteria enzymatically the polysaccharide (lactulose) into organic acid.

• This lowers the pH surrounding the system sufficient to effect the dissolution of the acid soluble coating and subsequent drug release.

05/01/2023 7

Osmotic Controlled Drug Delivery (OROS-CT)

05/01/2023 8

(OROS-CT)

• The OROS-CT system can be a single osmotic unit or may incorporate as many as 5-6 push-pull units, each 4 mm in diameter, encapsulated within a hard gelatin capsule.

• Each bilayer push pull unit contains an osmotic push layer and a drug layer, both surrounded by a semi permeable membrane.

• An orifice(6.35µm) is drilled through the membrane next to the drug layer

05/01/2023 9

(OROS-CT)

• Upon swelling the gelatin capsule dissolves.

• Drug impermeable enteric coating of push pull units prevent it from absorbing water in acidic environment.

• Upon entering small intestine the coating dissolves whereby, allowing absorption of water, causing the osmotic push compartment to swell concomitantly creates a flow-able gel in the drug compartment

05/01/2023 10

(OROS-CT)

• Swelling of the osmotic push compartment forces drug gel out of the orifice at a rate precisely controlled by the rate of water transport through the semi permeable membrane

• Materials used as – semi permeable materials- cellulose acylate, or cellulose

acetate– Osmopolymers- PVA, PVP– Enteric coating materials- pthalates bases.

05/01/2023 11

PULSINCAP System

05/01/2023 12

PULSINCAP System• It comprises of a water-insoluble capsule enclosing the drug

reservoir.• A swellable hydrogel plug was used to seal the drug contents

into the capsule body.• When this capsule came in contact with the dissolution fluid,

it swelled; and after a lag time, the plug pushed itself outside the capsule and rapidly released the drug.

• The length of the plug and its point of insertion into the capsule controlled the lag time.– Polymers for hydrogels –HPMC, PVA, PEO, PMA

05/01/2023 13

Hydrophilic sandwich capsule

• It is simply a capsule in capsule. • Within which the intracellular space is filled with hydrophilic

polymer, which created a hydrophilic sandwich between two capsules.

• When the outer shell dissolved the hydrophilic polymer provided a time delay before the fluid could enter the inner capsule and cause drug release.

• The time delay was controlled by the molecular weight of the polymers and it can also be further manipulated.

05/01/2023 14

PORT system

05/01/2023 15

PORT system

• It consists of a capsule coated with a semipermeable membrane.

• Inside the capsule was an insoluble plug(made up of waxes, fatty easters) consisting of osmotically active agent( mannitol, sorbitol etc,) and the drug formulation.

• The increased pressure due to swelling of osmogen forces the plug to slide out of the shell to release the drug.

05/01/2023 16

TIMECLOCK system

05/01/2023 17

TIMECLOCK system

• Based on solid dosage form that is coated by an aqueous dispersion.

• This coating is a hydrophobic surfactant layer to which a water soluble polymer is added to improve adhesion to the core.

• Upon contact with the dissolution fluid the dispersion rehydrates and redisperses.

• The lag time could be controlled by varying the thickness of the film. After the lag time, i.e; the time required for rehydration, the core immediately releases the drug.

05/01/2023 18

TARGITTM

• It is developed to deliver drugs for the topical treatment of the colonic diseases.

• The technology is based on the application of pH- Sensitive coatings onto injection-moulded starch capsules.

• An extensive body of clinical data has been generated showing reliable in vivo performance of the capsules.

• TARGIT based products are in active clinical development for the treatment of conditions including inflammatory bowel diseases.

05/01/2023 19

Chronotropic system

05/01/2023 20

Chronotropic system

• These systems are based upon a drug reservoir surrounded with a soluble barrier layer that dissolves with time and the drug releases at once after this lag time.

• Chronotropic system consists of a core containing reservoir coated by a hydrophilic polymer HPMC.

• An additional enteric-coated film is given outside this layer to overcome intra subject variability in gastric emptying rates

• The lag time and the onset of action are controlled by the thickness and the viscosity grade of HPMC.

05/01/2023 21

Enterion capsule Technology• Long, round-ended capsule and contains a drug reservoir with

a volume capacity of approximately 1 ml. • The capsule can be loaded with either a liquid formulation

through an opening 9 mm in diameter, which is then sealed by inserting a push-on Cap fitted with a silicone O-ring.

• A radioactive marker is placed inside a separate sealed tracer port to allow real time visualization of the capsule location using the imaging technique of gamma Scintigraphy.

• Upon reaching the target site in GI tract, the contents are actively ejected by the external application of an oscillating magnetic field.

05/01/2023 22

COLALTM

• COLAL-PRED has a coating that is broken down only in the colon, by locally occurring bacteria.

• COLAL-PRED is a proprietary gastrointestinal product developed by alizyme for the treatment of ulcerative colitis (US).

• This leads to topical delivery of prednisolone to the colon without significant systemic exposure so minimizing steroid related side effects.

• It is ethyl-cellulose and amylase film coating based system, in which amylase works in pore forming agent and EC act as release control matrix agent via swelling or enzyametic degradation.

05/01/2023 23

EGALET TECHNOLOGY

• It offers two systems the constant release 2K system and delayed release 3K system.

• The 2K system consists of two compartments: an impermeable coat and matrix.

• The drug is distributed throughout the matrix and it release the drug as it passes through the gut.

05/01/2023 24

EGALET TECHNOLOGY

• The 3K comprises of impermeable shell and two lag plugs. • Enclosing the active drug into two lags.

• The active drug releases after the lags are removed causing a delay in the drug release.

05/01/2023 25

References

• K.V. Vinaykumar et al. “Colon targeting drug delivery system: A review on recent approaches. Int J Pharm Biomed Sci 2011.

• R.J. Michael et al. modified release drug delivery system, informa healthcare volume 1 second edition P.No. 287-356.

05/01/2023 26

THANK YOU