GRDDS (teksed).ppt

8/18/2019 GRDDS (teksed).ppt

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Gastroretentive

Drug Delivery Systems(GRDDS)


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Gastroretentive Drug Delivery

Systems (GRDDS)

• Dosage forms that can be retained in the stomach

are called gastroretentive drugdelivery systems(GRDDS) .

• GRDDS can improve the controlled delivery of

drugs that have an absorption window by

continuously releasing the drug for a prolonged

period of time before it reaches its absorption site,

thus ensuring its optimal !.


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Gastroretentive techniques

Several techni"ues, including

• floating

• swelling,

• io#mocoadhesion


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$loating systems

• $loating systems, first described by Davis in %&',are low density systems that have sufficient‑

buoyancy to float over the gastric contents andremain in the stomach for a prolonged period

(*,+).• hile the system floats over the gastric contents,

the drug is released slowly at the desired rate (-,'), which results in increased GR and reduces

fluctuation in plasma drug concentration (/).• $loating systems can be classified as effervescent

and noneffervescent systems.


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Effervescent systems

• $lotation of a drug delivery system in the stomachcan be achieved by incorporating a floating

chamber filled with vacuum, air, or an inert gas.

• Gas can be introduced into the floating chamber

by the volatili0ation of at) organic solvent (e.g.,

ether or cyclopentane) or by the 12, produced as a

result of an effervescent reaction between organicacids and carbonate bicarbonate salts‑


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• hese devices contain a hollow deformable unit

that converts from a collapsed to an e3panded

position and returns to the collapsed position after

a predetermined amount of time to permit the

spontaneous e4ection of the inflatable system from

the stomach.


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Noneffervescent systems

• 5oneffervescent systems incorporate a high level(6 /-7 w#w) of one or more gel forming, highly‑ ‑

swellable,8

• cellulosic hydrocolloids (e.g., hydro3yethyl

cellulose, hydro3ypropyl cellulose, 9:;1, andsodium carbo3ymethylcellulose),

• polysaccharides,or

• matri3 forming polymers (e.g., polycarbophil,‑:olyacrylates, and polystyrcne) into tablets or

capsules.


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•


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io#mucoadhesive systems

• io#mucoadhesive systems bind to the gastricepithelial cell surface, or mucin, and e3tend the GR

by increasing the intimacy and duration of contact between the dosage form and the biologicalmembrane.

• he concept is based on the self protecting‑mechanism of the G=. ;ucus secreted continuously

by the speciali0ed goblet cells located throughout theG= plays a cytoprotective role.

• ;ucus is a viscoclastic, gel li>e, stringy slime‑comprised mainly of glycoproteins. he thic>ness ofthe mucus layer decreases from the membranesurface to the G= lumen.


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• he primary function of mucus is to protect the

surface mucosal cells from acid and pepticlases. =naddition, it serves as a lubricant for the passage ofsolids and as a barrier to antigens, bacteria, andviruses .

• he epithelial adhesive properties of mucin arewell >nown and have been applied to thedevelopment of GRDDS through the use of

bio#mucoadhesive polymers . he adherence of the

delivery system to the gastric wall increasesresidence time at a particular site, therebyimproving !


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• ! bio#mucoadhesive substance is a natural orsynthetic polymer capable of adhering to a

biological membrane (bioadhesive polymer) or themucus lining of the G= (mucoadhesive polymer).

• he characteristics of these polymers aremolecular fle3ibility, hydrophilic functional

groups, and specific molecular weight, chainlength, and conformation.

• $urthermore, they must be nonto3ic andnonabsorbable, form noncovalen bonds with the

mucin epithelial surfaces, have "uic> adherence to‑moist surfaces, easily incorporate the drug, offer

no hindrance to drug release, have a specific siteof attachment, and be economical


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• he binding of polymers to the mucinepithelia?surface can be subdivided into three broadcategories8

a. hydration mediated adhesion,‑

b. bonding mediated adhesion, and‑

c. receptor mediated adhesion.‑

1. Hydration mediated adhesion‑

.1ertain hydrophilic polymers tend to imbibe largeamount of water and become stic>y, therebyac"uiring bioadhesive properties. he prolonged

gastroretention of the bio#mucoadhesive drugdelivery system is further controlled by thedissolution rate of the polymer.


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2. Bonding mediated-adhesion‑ .

he adhesion of polymers to a mucus or epithelialcell surface involves various bonding mechanisms,

including physical mechanical bonding and‑

chemical bonding.

a) :hysical mechanical bonds can result from the‑insertion of the adhesive material into the crevices or

folds of the mucosa. b) 1hemical bonds may be either covalent (primary) or

ionic (secondary) in nature. Secondary chemical bonds consist of dispersive interactions (i.e., van der

aals interactions) and stronger specific interactionssuch as hydrogen bonds. he hydrophilic functionalgroups responsible for forming hydrogen bonds arethe hydro3yl and carbo3ylic groups ().


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• Receptor mediated-adhesion.‑

1ertain polymers can bind to specific receptor sites

on the surface of cells, thereby enhancing the gas

tric retention of dosage forms. 1ertain plant lectins

such as tomato lectins interact specifically with

the sugar groups present in mucus or on the

glycocaly3.


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Swelling systems

• !fter being swallowed, these dosage forms swellto a si0e that prevents their passage through the

pylorus . !s a result, the dosage form is retained in

the stomach for a long period of time.

• hese systems are sometimes referred to as plug

type systems because they tend to remain lodged

at the pyloric sphincter. hese polymeric matrices

remain in the gastric cavity for several hours evenin the fed state.


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• Sustained and controlled drug release may beachieved by selecting a polymer with the propermolecular weight and swelling properties. s in the hydrophilic‑

polymer networ>.

• hese cross lin> prevent the dissolution of the‑ polymer and thus maintain the physical integrity of

the dosage form. ! balance between the e3tent andduration of swelling is maintained by the degree ofcrosslin>ing between the polymeric chains.


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• ! high degree of crosslin>ing retards the swellingability of the system and maintains its physical

integrity for a prolonged period ($igure). 2n theother hand, a low degree of cross lin>ing results in‑e3tensive swelling followed by the rapiddissolution of the polymer .

• !n optimum amount of cross lin>ing is re"uired‑to maintain a balance between swelling and

dissolution. he swollen system eventually willlose its integrity because of a loss of mechanical

strength caused by abrasion or erosion or will burst into small fragments when the membraneruptures because of continuous e3pansion .


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hese systems also may erode in the presence of

gastric 4uices so that after a predetermined time the

device no longer can attain or retain the e3panded

configuration.


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9igh density systems‑

• hese systems, which have a density of *

g#cm*, are retained in the rugae of the

stomach and are capable of withstanding its peristaltic movements .

• !bove a threshold density of .+ . g#cm‑ *,

such systems can be retained in the lower part of the stomach .


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Evaluation of GRDDS

1. Floating systems

2. Bio/mucoadhesion systems

3. Swelling systems


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Floating systems

1. Floating/uoyancy time.

he test for buoyancy is usually determinedin &66 m@ of simulated gastric (91=#5a1l

with 6.67 Tween 80, p9 %.) or intestinalfluids (A9:2+#5a29 buffer with 6.67

ween 6, p9 /.+) maintained at */o1using the


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• he amount of time the dosage form floats is

termed t hefloating time . =n the case of floatingmicroparticles, the number of floating particles

and the time during which they remain buoyant on

the test solution can be determined.

• he floating process depends on the balance

between the weight and volume of the dosage

form. !n increase in the buoyancy force caused by

the increased volume causes a resultant weight

increase and leads to dosage form flotation .‑


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2. S!eci"ic gravity.

he specific gravity of floating systems can be

determined by the displacement method, usingbenzene as a displacing medium .

3. #esultant weight.

density and floating durationhave been the main parameters to describe the

ade"uacy of a dosage formBs buoyancy,

9owever, although the density value may

indicate whether or not an ob4ect will float, thedensity value does not reflect the magnitude of

floating force produced by the ob4ect


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• herefore, an in vitro measuring apparatus has been conceived to determine the real floating

capabilities of buoyant dosage forms as a functionof time. it operates by measuring the forcee"uivalent to the force $ re"uired to >eep theob4ect totally submerged in the fluid. his force

determines the resultant weight of the ob4ect whenimmersed and may be used to "uantify its floatingor nonfloating capabilities.

• he magnitude and direction of the force and the

resultant weight corresponds to the vectorial sumof buoyancy (Fbuoy ) and gravity ($grav) forcesacting on the ob4ect as shown in the e"uation


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$ C $ buoy $‑ grav

F = d f gV d ‑

s gV (d ‑

f d ‑

s ) gV F = (d f M/V) gV ‑

• in which $ is the total vertical force(resultant weight of the ob4ect), g is the

acceleration due to gravity, df is the fluid

density, is the ob4ect density, M is theob4ect mass, and E is the volume of the

ob4ect.


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• y convention, a positive resultant weight

signifies that the force $ is eerted !"ward andthat the ob4ect is able to float, whereas a negativeres!ltant weight means that $ acts downward andthat the ob4ect sin>s.

• he crossing of the 0ero base line by the resultantweight curve from positive toward negative valuesindicates a transition of the dosage form fromfloating to nonfloating conditions.

• he intersection of lines on a time a3iscorresponds to the floating time of the dosageform


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Bio/mucoadhesion systems

• ioachesive strength.

he bioadhesive strength of a polymer can be

determined by measuring the force re"uired to se"arate the polymer specimen sandwiched

between the layers of either an artificial (e.g.,

cellophane) or biological (e.g., rabbit stomach

tissue) membrane .his force can be meas!red b#using a modified precision balance or an auto

mated tet!re anal#zer .


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Swelling systems

• $eight gain and water upta>e (


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< is meas!red in terms of percent weight

gain, as given by the e"uation

< C (t o)‑ X %66#o

• in which $t and o, are the weights of thedosage form at time t and initially,

respectively.


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GRDDS (teksed).ppt

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