Professional Documents
Culture Documents
Ans) Improved patient convenience and compliance due to less frequent drug
administration.
a. Size d) intercellular
a. Prodrugs
Ans:
1. 1Hollow microspheres loaded with drug in their outer polymer shelf were prepared by
a novel emulsion solvent diffusion method.
2.The ethanol/dichloromethane solution of the drug and an enteric acrylic polymer is
poured into an agitated solution of Poly Vinyl Alcohol (PVA) that was thermally controlled
at 40ºC.
3.The gas phase is generated in the dispersed polymer droplet by the evaporation of
dichloromethane formed and internal cavity in the microsphere of the polymer with drug.
4.The microballoon floats continuously over the surface of an acidic dissolution media
containing surfactant for more than 12 hours.
Ans:
1.This system contains drug with gel-forming hydrocolloids meant to remain buoyant on
the stomach content.
2.This prolongs GRT and maximizes the amount of drug that reaches its absorption sites
in the solution form for ready absorption.
3.This system incorporates a high level of one or more gel-forming highly soluble
cellulose type hydrocolloid, e.g hydroxypropyl cellulose, hydroxyethyl cellulose,
hydroxypropyl methyl cellulose (HPMC), polysaccharides and matrix-forming polymer
such as polycarbophil, polyacrylate and polystyrene.
4.On coming in contact with gastric fluid, the hydrocolloid in the system hydrates and
forms a colloid gel barrier around its surface.
5.This gel barrier controls the rate of fluid penetration into the device & consequent
release of drug.
c.Alginate beads
Ans:
1.Multi-unit floating dosage forms have been developed from freeze-dried calcium
alginate.
Ans:
2.The peripheral walls of the drug reservoir compartment are completely sealed to
prevent any direct contact of gastric surface with the undissolved drug.
3.In the stomach, the floatation chamber containing entrapped air causes the delivery
system to float over the gastric content.
4.Gastric fluid enters through the aperture, dissolves the drug and carries the dissolved
drug for continuous transport across the intestine for absorption.
e. V
olatile liquid containing systems
Ans:
These devices are osmotically controlled floating systems containing a hollow deformable
unit that can convert from a collapsed to an expanded position & returns to collapsed
position after an extended period.
The first chamber contains the drug & the second chamber contains volatile liquid.
The device inflates & the drug is continuously released from the reservoir into the gastric
fluid.
The device may also contain a bioerodible plug made up of PVA, PE that gradually
dissolves causing the inflatable chamber to release gas & collapse after a predetermined
time to permit the spontaneous ejection of the inflatable system from the stomach
Ans:
These devices are osmotically controlled floating systems containing a hollow deformable
unit that can convert from a collapsed to an expanded position & returns to collapsed
position after an extended period.
The first chamber contains the drug & the second chamber contains volatile liquid.
The device inflates & the drug is continuously released from the reservoir into the gastric
fluid.
The device may also contain a bioerodible plug made up of PVA, PE that gradually
dissolves causing the inflatable chamber to release gas & collapse after a predetermined
time to permit the spontaneous ejection of the inflatable system from the stomach
These tablets may be either single layered wherein the CO2 generating components are
compressed in one hydrocolloid containing layer, & the drug in the other layer formulated
for a SR effect.
The inner layer - an effervescent layer containing NaHCO3 & tartaric acid
Effervescent layer is divided into two sub layers to avoid direct contact between NaHCO3
& tartaric acid
When the system is immersed in the buffer solution at 37°C, swollen pills like balloons
are formed having density less than 1gm/ml.
This occurs due to the CO2 by neutralization of the inner effervescent layer with the
diffusion of water through the outer swellable membrane layer
These kinds of system float completely with 10 minutes, & remain floating over extended
periods of 5-6 hours.
5. What is the need for development of Floating Gastro retentive DDS? (4M)
Ans:
•Superior to single unit floating dosage forms as such microspheres release drug
uniformly.
6. What are the evaluation tests for Floating Gastro retentive DDS? (4M)
Ans:
1. Floating time
1.The test for floating time measurement is usually performed in stimulated gastric fluid
or 0.1M HCl maintained at 37°C.
2.It is determined by using USP dissolution apparatus containing 900ml of 0.1M HCl as
the dissolution medium at 37°C.
3.The time taken by the dosage form to float is termed as floating lag time and the time for
which the dosage form floats is termed as the floating or flotation time
2. Specific gravity
It can be measured by the displacement method using benzene as a displacing medium
3. Resultant weight test:
1.An in vitro measuring apparatus has been conceived to determine the real floating
capabilities of buoyant dosage forms as a function of time.
2.It operates by measuring the force equivalent to the force F required to keep the object
totally submerged in the fluid .
3.This force determines the resultant weight of the object when immersed and may be
used to quantify its floating or nonfloating capabilities.
4.The magnitude and direction of the force and the resultant weight corresponds to the
vectorial sum of buoyancy ( F bouy ) and gravity ( F grav ) forces acting on the object as
shown in the equation
F = F buoy – F grav
F = d f gV
– d s gV
= (d f - d s ) gV
F = (df – M / V) gV
F is the total vertical force (resultant weight of the object),
g is acceleration due to gravity,
d f is the fluid density,
d s is
the object density,
M is the object mass, and
V is the volume of the object .
5.By convention, a positive resultant weight signifies that the force F is exerted upward
and that the object is able to float, whereas a negative resultant weight means that the
force F acts downward and that the object sinks.
6.The crossing of the zero base line by the resultant weight curve from positive toward
negative values indicates a transition of the dosage form from floating to nonfloating
conditions.
7.The intersection of lines on a time axis corresponds to the floating time of the dosage
form.
B) Swelling System
1)Weight gain & water uptake
1.The swelling behavior of dosage unit can be measured by either by studying its
dimensional changes, weight gain or water uptake.
2.It is done by immersing the dosage from in the simulated gastric fluid at 37°C &
determining these factors at regular intervals.
3.The dimensional changed can be measured in increase in the tablet diameter &/or
thickness with time.
4.Water uptake is measured in terms of % weight gain as given by-
Wt & Wo are the weight of the dosage forms at time t & initially
2)Drug release:
1.Dissolution tests are performed using the dissolution apparatus.
2.Samples are withdrawn periodically from the dissolution medium with replacement and
then analyzed for their drug content after an appropriate dilution.
3)In-vivo methods of evaluation of GRDF
1. γ-Scintigraphy
1.γ-Scintigraphy can be use to evaluate in-vivo buoyancy and in-vivo release performance
of different type of GRDF.
In is formulated within the developed
2.In this technology a stable radioisotope like 111
system and administered in healthy human volunteers.
3.Major drawbacks with such a technique are associated ionization radiations, limited
topographic information, low resolution, and complicated and expensive preparation of
radiopharmaceuticals.
2. Radiology
1.This method includes pre-clinical estimation of gastroretention.
ore simple and cost effective
2.In comparison to γ-scintigraphy, radiology is a m
technique.
3.However, limitations regarding exposure to X-rays decline its popularity because for
optimum evaluation of buoyancy a high amount of contrasting agent (BaSO4) is generally
required.
4.Radiographs were taken after ingestion of the dosage form, to locate the floating and
non-floating (fabricated) dosage forms at various periodic time intervals.
3. Gastroscopy
1.This is considered a minimally invasive procedure since it does not require an incision
into one of the major body cavities.
2.This technique involves visual inspection of GRDF in the stomach.
3.Basically it is a type of peroral endoscopy which comprises optic fibers and a video
camera.
4.For more detailed information the evaluated system can be drawn out from the
stomach.
5.However, on the other hand the quality of study and its interpretation are highly
dependent on the expertise of the endoscopist.
6.Active uncontrolled bleeding, retained blood in the stomach, and retained food or
antacids may also lead to an inadequate study.
7. W
hat is the significance of developing Colon Targeted DDS? (2M)
Ans:
1. The site specific delivery of drug to lower part of GIT for localised treatment of several
colonic disease (ulcerative colitis, crohns disease, carcinomas and infection)
2.Prevent drug from degradation.
3.Ensure direct treatment at disease site.
4.Suitable absorption site for protein and peptide drug.
5.Used to prolong the drug therapy.
6.Improve drug utilisation.( write about chronotherapeutics)
Ans :
Eudracol is a colon targetted pH Triggered and sustained released oral drug delivery
technology for multiunit dosage forms, for both for local and systemic therapies.
9. How does Microbiologically Triggered drug delivery to colon works? (4M)
Ans.
•The microflora of the colon is in the range of 1011 -1012 CFU/ mL, consisting mainly of
anaerobic bacteria, e.g. bacteroides, bifidobacteria, eubacteria, clostridia, enterococci,
enterobacteria and ruminococcus etc.
•Presence of the biodegradable enzymes only in the colon, the use of biodegradable
polymers for colon-specific drug delivery.
•These polymers shield the drug from the environments of stomach and small intestine, and
are able to deliver the drug to the colon.
PRODRUG -
•A Prodrug is a pharmacologically inactive derivative of a parent molecule that require some
form of transformation in vivo to release the active drug at the target site.
•This approach involves covalent linkage between the drug and its carrier.
•Biotransformation is carried out by a variety of enzymes, mainly of bacterial origin, present
in the colon. The enzymes that are mainly targeted for colon drug delivery include
azoreducatase - galactosidase, βxylosidase, nitroreductase, glycosidase deaminase, etc.
•For colonic delivery , prodrug is designed to undergo minimal hydrolysis in upper tracts of
GIT & undergo enzymatic hydrolysis in colon there by releasing the active drug moiety from
drug moiety.
The azo linkage exhibit a wide range of thermal, chemical, photochemical and
pharmaceutical properties.
Sulphasalazine, which was used for the treatment of rheumatoid arthritis. This compound has
an azo bond between 5-ASA and sulphapyridine.
Include naturally occurring polysaccharides obtained from plant (guar gum, inulin), animal
(chitosan, chondrotin sulphate), algal (alginates) or microbial
(dextran) origin.
The polysaccrides can be broken down by the colonic microflora to simple saccharides.
Therefore, they fall into the category of “generally regarded as safe.
2)Polysaccharidase :
The colonic microflora secretes a number of enzymes that are capable of hydrolytic cleavage of
glycosidicbonds.
Natural polysaccharides like pectin & inulin are not digested in stomach & small intestine but
are degraded in colon by resident bacteria.
10. Describe Pulsincap in detail. (4M)
Ans :
•Solutions of different concentrations having the same solute and solvent system
exhibit an osmotic pressure proportional to their concentrations.
•Thus a constant osmotic pressure, and thereby a constant influx of water can be
achieved by an osmotic delivery system that results in a constant zero order release
rate of drug.
12. Explain the general mechanism for drug release from osmotic pump. (4M)
Ans :
•When the osmotic pressure of the formulation is large compared to the osmotic
pressure of the environment, p can be substituted for Dp. dV/dt = A/h Lp σπ = A/hk
π
(k = Lpσ = membrane permeability)
Now, equation (1) can be given as dM/dt = (A/h) k π c = (A / h) k π S
Ans :
Components of Osmotic DDS
● Drug
● Osmotic agent
● Semi permeable membrane
● Plasticizers
1.Drugs :
A.Characteristics of drug candidate for osmotically controlled drug delivery
B.Short biological half-life (2-6h)
C. Highly potent drug
D. Required for prolonged treatment e.g. Nifedipine, Glipizide, Virapamil.
2.Osmotic agents :
A.Osmogents used for fabrication of osmotic dispensing device are inorganic or organic in
nature, a water soluble drug by itself can serve the purpose of an osmogent.
B.Inorganic water-soluble osmogents
Magnesium sulphate, Sodium chloride, Sodium sulphate, Potassium chloride, Sodium
bicarbonate.
C.Organic polymer osmogents
Sodiumcarboxymethylcellulose, Hydroxypropylmethyl
cellulose,Hydroxyethylmethylcellulose, Methylcellulose, Polyethylene oxide, polyvinyl
pyrollidine.
3.Semi Permeable Membrane :
A.The semi permeable membrane should be a stable both to the outer inner environment
of the device.
B. The membrane must be sufficiently rigid so as to retain its dimensional integrity during
the operational lifetime of the device.
C.The membrane should also be relatively impermeable to the contents of dispenser so
that osmogent is not lost by diffusion across the membrane.
D. The membrane must be biocompatible.
Ideal Property of Semi Permeable Membrane:
•The material must possess sufficient wet strength (~105 psi) and wet modulus (~105
psi) so as to retain its dimensional integrity during the operational lifetime of the device.
•The membrane exhibit sufficient water permeability so as to retain water flux rate in the
desired range. The water vapor transmission rates can be used to estimate water flux
rates.
•The reflection coefficient (σ) and leakiness of the osmotic agent should approach the
limiting value of unity. Unfortunately, polymer membranes that are more permeable to
water are also, in general more permeable to the osmotic agent.
•The membrane should also be biocompatible
•Rigid and non-swelling
•Should be sufficient thick to withstand the pressure within the device.
4.Plasticizers :
A.Different types and amount of plasticizers used in coating membrane also have a
significant importance in the formulation of osmotic systems.
B. They can change visco-elastic behavior of polymers and these changes may affect the
permeability of the polymeric films.
C. Some of the plasticizers used are as below:
•Polyethylene glycols
•Ethylene glycol monoacetate; and diacetate- for low permeability
•Tri ethyl citrate
•Diethyl tartarate or Diacetin- for more permeable films
14. What are the ideal properties of semi permeable membranes used in
osmotically controlled DDS? (2M)
Ans :
•The material must possess sufficient wet strength (~105 psi) and wet modulus (~105 psi) so
as to retain its dimensional integrity during the operational lifetime of the device.
•The membrane exhibit sufficient water permeability so as to retain water flux rate in the
desired range. The water vapor transmission rates can be used to estimate water flux rates.
•The reflection coefficient (σ) and leakiness of the osmotic agent should approach the
limiting value of unity. Unfortunately, polymer membranes that are more permeable to water
are also, in general more permeable to the osmotic agent.
•The membrane should also be biocompatible
•Rigid and non-swelling
•Should be sufficient thick to withstand the pressure within the device.
The pump can be made with single or multicompartment dosage form, in either form, the
delivery system comprises a core with the drug surrounded by a membrane which has an
asymmetric structure, i.e. comprises a thin dense skin layer supported by a porous
substructure.
Membrane is permeable to water but impermeable to solute and insensitive pore forming
additive dispersed throughout the wall.
When exposed to water, low levels of water-soluble additive are leached from polymer
materials that were permeable to water yet remained insoluble.
Then resulting sponge like structure formed the controlled porosity walls of interest and
was substantially permeable to both water and dissolved drug agents.
Rate of drug delivery depends upon the factors are water permeability of the semi
permeable membrane and the osmotic pressure of the core formulation, thickness and
total surface area of coating.
All of these variable are under the control of the designer and do not vary under
physiological condition, leading to the robust performance
The rate of flow dv/dt of water into the device can be represented as
dv / dt = Ak / h (Dp-DR)
This system is similar to an EOP expect delivery orifice is absent and size may be smaller.
Liquid OROS are designed to deliver drugs as liquid formulations and combine the
benefits of extended release with high bioavailability.
The expansion of the osmotic layer results in the development of hydrostatic pressure
inside the system, thereby forcing the liquid formulation to be delivered from the delivery
orifice.
The delayed liquid bolus delivery system comprises three layers: a placebo delay layer, a
liquid drug layer and an osmotic engine, all surrounded by rate controlling semi
permeable membrane.
The delivery orifice is drilled on the placebo layer end of the capsule shaped device.
When the osmotic engine is expands, the placebo is released first, delaying release of the
drug layer.
Drug release can be delayed from I to 10 hour, depending on the permeability of the rate
controlling membrane and thickness of the placebo layer.
It is composed of polymeric push layer sandwiched between two drug layers with two
delivery orifices.
When placed in the aqueous environment the middle push layer containing the swelling
agents swells and the drug is released from the two orifices situated on opposite sides of
the tablet and thus SOTS can be suitable for drugs prone to cause local irritation of the
gastric mucosa.
Water imbibtion by the active agents takes place rupturing the polymer matrix capsule
surrounding the drug, thus liberating it to the outside environment.
Initially this process occurs at the outer environment of the polymeric matrix, but
gradually proceeds towards the interior of the matrix in a serial fashion.
However this system fails if more then 20 –30 volume per liter of the active agents is
incorporated in to the device as above this level, significant contribution from the simple
leaching of the substance take place.
9. OSMAT.
Ans:
It is a novel osmotically driven matrix system, which utilizes the hydrophilic polymers to
swell, and gel in aqueous medium forming a semipermiable membrane in-situ.
Release from such a matrix system containing an osmogen could, therefore be modulated
by the osmotic phenomenon.
Osmat produces controlled drug release with adequate delivery rates in an agitation in
dependent manner.
Thus osmat represents simple, versatile, and easy to fabricate osmotically driven
controlled drug delivery system based upon low cot technology.
In 1955 two Australian physiologist Rose and Nelson reported the first osmotic pump.
They were interested in delivery of drugs to the gut of sheep and cattle. It consist of,
● A water chamber.
The drug and salt chamber are separated by a rigid semipermeable membrane.
The difference in osmotic pressure across the membrane moves water from the water
chamber into salt chamber.
The volume of the salt chamber increases because of this water flow, which distends the
latex diaphragm
separating salt and drug chamber there by pumping drug out of this device.
The pumping rate of Rose-Nelson pump is given by the equation:
dm/dt = dv/dt *C
Where:
dm/dt = Drug release rate. dv/dt = Volume flow of water into salt chamber.
The above equation equation can be used to describe the behavior of all the devices.
Osmotic pressure of saturated salt solution is high, small pressure required to pump the
suspension of active agent is insignificant.
Thus water permeation across the membrane remains constant as long as sufficient salt is
present, hence a constant osmotic pressure driving force.
•The semi permeable wall itself act as a rigid outer casing of the pump .
•The device is loaded with drug prior to use. When the device is put in an aqueous
environment the release of the drug follows a time course set by the salt used in
the salt chamber and the permeability of the outer membrane casing.
•The design of Higuchi Leeper pump represents the first simplified version of the
Rose Nelson pump made by the Alza Corporation in the early 1970.
•It contains a rigid housing and the semipermeable membrane which is supported
on a perforated frame. Rigid housing is divided in two chambers by a movable
separator.
•The benefit of this pump over Rose Nelson pump is that it does not have water
chamber and the device is activated by water imbibed from the surrounding
environment.
•It is composed of three concentric layers- the drug reservoir, the osmotic sleeve
and the rate controlling semipermeable membrane.
•The additional component called the flow moderator is inserted into the body of
the osmotic pump after filling.
•When the system is placed in aqueous environment water enters the sleeve
through semipermeable membrane, compresses the flexible drug reservoir and
displaces the drug solution through the flow moderator.
•These pumps are available with a variety of delivery rate between 0.25 to 10 ml
per hour and delivery duration between 1 day and 4 weeks.
•The elementary osmotic pump is a new delivery system for drugs. It delivers the agent
by an osmotic process at a controlled rate.
1.In its simplest embodiment the system is constructed by coating an osmotically active
agent with the rate controlling semipermeable membrane.
2.This membrane contains an orifice of critical size through which agent is delivered.
3.The dosage form after coming into contact with aqueous fluids, imbibes water at a rate
determined by the fluid permeability of the membrane and osmotic pressure of the core
formulation.
•This osmotic imbibitions of water result in formation of a saturated solution of drug
within the core, which is dispensed at controlled rate from the delivery orifice in the
membrane.
•Though 60 -80 percent of drug is released at a constant rate from the EOP, a lag time of
30-60 minute is observed in most of the cases as the system hydrates before zero order
delivery from the system begins.
•These system are suitable or delivery of drugs having moderate water solubility.
•Push pull osmotic pump is a modified EOP. through, which it is possible to deliver both
poorly water-soluble and highly water soluble drugs at a constant rate.
•One layer (depict as the upper layer) contains drug in a formulation of polymeric,
osmotic agent and other tablet excipients. This polymeric osmotic agent has the ability to
form a suspension of drug in-situ when this tablet later imbibes water.
•The other layer contains osmotic and colouring agents, polymer and tablet excipients.
These layers are formed and bonded together by tablet compression to form a single
bilayer core.
•After the coating has been applied, a small hole is drilled through the membrane by a
laser or mechanical drill on the drug layer side of the tablet.
•When the system is placed in aqueous environment water is attracted into the tablet by
an osmotic agent in both the layers.
•The osmotic attraction in the drug layer pulls water into the compartment to form in situ
a suspension of drug.
•The osmotic agent in the non-drug layer simultaneously attract water into that
compartment, causing it to expand volumetrically and the expansion of non drug layer
pushes the drug suspension out of the delivery orifice.
•This group can be divided into two sub groups, depending on the function of second
chamber.
•In one category of these devices, the second chamber is used to dilute the drug solution
leaving the devices.
•This is useful because in some cases if the drug leaves the oral osmotic devices a
saturated solution, irritation of GI tract is a risk. Example: - the problems that lead to
withdrawal of osmosin,
•The device consists of a normal drug containing porous tablet from which drug is
released as a saturated solution. However before the drug can escape from the device it
must pass through a second chamber.
•Water is also drawn osmotically into this chamber either because of osmotic pressure of
drug solution or because the second chamber contain, water soluble diluents such as
NaCl.
•This type of devices consist of two rigid chamber, the first chamber contains a
biologically inert osmotic agent, such as sugar or a simple salt like sodium chloride, the
second chamber contains the drug.
•In use water is drawn into both the chamber through the surrounding semi permeable
membrane.
•The solution of osmotic agent formed in the first chamber then passes through the
connecting hole to the drug chamber where it mixes with the drug solution before exiting
through the micro porous membrane that form a part of wall surrounding the chamber.
17 .Theories of mucoadhesion
● Electronic theory
● Wetting theory
● Adsorption theory
● Diffusion theory
● Fracture theory
• Electronic theory
-Attractive electrostatic forces between glycoprotein mucin network & the bioadhesive
material.
• Wetting theory
-Ability of bioadhesive polymers to spread & develop intimate contact with the mucous
membrane.
• Adsorption theory
-Surface forces ( covalent bond, ionic bond, hydrogen bond & van der waals forces)
resulting in chemical bonding
• Diffusion theory
•Fracture theory
-Analyses the maximum tensile stress develop during detachment of the BDDS from
mucosal surfaces
16. What are the factors affecting Drug Release Rate from Osmotic Systems? (4M)
Ans:
1.Solubility:
APIs for osmotic delivery should have water solubility in the desired range to get optimize
drug release. Candidate drug for osmotic delivery should have solubility within the range
of 50- 300 mg/ml.
However, by modulating the solubility of these drugs within the core, effective release
patterns may be obtained.
Solubility-modifying approaches:
•Use of crystal habit modifiers: Different crystal form of the drug may have different
solubility, so the excipient which may change crystal habit of the drug can be used to
modulate solubility.
2.Osmotic pressure :
The next release-controlling factor that must be optimized is the osmotic pressure
gradient between inside the compartment and the external environment.
The osmotic pressure can also be found out by the Van’t Hoff equation:-
π = CRT
T = Absolute temperature.
The simplest and most predictable way to achieve a constant osmotic pressure is to
maintain a saturated solution of osmotic agent in conmpartment.
Drug release from an osmotic system is largely independent of the pH and agitation
intensity of GIT tract.
This is because of its selective water permeable membrane and effective isolation of
dissolution process of drug core from the gut environment.
The in–vivo release rate of the system is therefore independent of its position in the GIT,
because the membrane in the osmotic system is semi permeable in nature any polymer
that is permeable to water but impermeable to solute (drug, organic and inorganic ions)
can be selected example include cellulose ester such as cellulose acetate, cellulose
diacetate, cellulose triacetate, cellulose propionate, and cellulose ether such as ethyl
cellulose and Eudragit.
The permeability of this membrane can be increased further by adding plasticizer to the
polymer, which increases the water diffusion coefficient or hydrophilic flux enhancer
which increases the water sorption of the membrane.A few example of hydrophilic flux
enhancer are Polyethylene glycols 300, 400, 600, 1500, 4000, and6000(Ramakrishna,
2001)
4. Membrane thickness :
A principle factor controlling the rate of penetration of water into the dispenser is the
thickness of the membrane.
The permeability of water into the membrane can be enhanced by the choice of a suitable
type of the membrane material.
The time of release of the active constituent can be easily varied by as much as 1000 fold
based upon the thickness of the membrane.
In general the rate of drug release can be achieved by varying the membrane material,
while small change up to a five percent can be best achieve by varying the thickness of the
membrane.
To achieve an optimal zero order delivery profile, the cross sectional area of the orifice
must be smaller than a maximum size to minimize drug delivery by diffusion through the
orifice.
Furthermore, the area must be sufficiently large, above a minimum size to minimize
hydrostatic pressure build up in the system.
The typical orifice size in osmotic pumps ranges from 600µ to 1 mm.
17. W
hat are the essential characteristics of Ocular Inserts? (4M)
Essential Requirements.....
• Physician acceptance;
• User acceptance;
• Patient comfort;
• Lack of toxicity;
• Sterility;
• Stability;
• Ease of manufacture;
• Reasonable price;
Lacrisert :
It is a sterile, translucent rod shaped device made of HPC without any preservative is used
for treatment of dry eye syndrome
The device is introduced by Merck, Sharp & Dohme
It is useful in treatment of patients with keratitis sicca whose symptoms are difficult to
treat with artificial tear alone
It is inserted into the inferior fornix where it imbibes the water from the conjunctiva &
cornea, forms a hydrophilic film which stabilizes the tear film & hydrates, lubricates
cornea.
Day long relief from dry eye syndrome is reported from a single insert placed in the eye
early in the morning.
SODI :
Soluble Ophthalmic Drug Insert (SODI) is a small oval wafer developed by Soviet
scientists.
The unit is made from acrylamide, N-vinylpyrrolidone & ethylacrylate (ratio 0.25 : 0.25 :
0.5).
It weighs 15-16mg which is placed in the inferior cul-de-sac where wetted by the tear
film, it softens in 10-15 seconds & assumes the curved configuration of the globe.
The film turns into a viscous polymer mass, thereafter in 30-60 minutes it becomes
polymer solution.
A single SODI application constitutes once a day therapy for the treatment of glaucoma.
OTS or Minidisc :
It consists of a contoured disc with a convex front & a concave back surface in the contact
with the eye ball.
The OTS can be hydrophilic or hydrophobic to permit the release of both water soluble &
insoluble drugs.
Advantages :
• Increased ocular residence, hence a prolonged drug activity and a higher bioavailability
with respect to standard vehicles;
• Accurate dosing (contrary to eye drops that can be improperly instilled by the patient
and are partially lost after administration,each insert can be made to contain a precise
dose which is fully retained at the administration site);
• Reduction of systemic absorption (which occurs freely with eye drops via the
nasolacrimal duct and nasal mucosa);
20. E
xplain non-erodible ocular inserts in detail. (4M)
1. Ocusert®
Retaining ring of EVA(Ethylene Vinyl Acetate) impregnated with Ti02 for visibility
purpose
It is preprogrammed to release pilocarpine at constant rate 20 or 40 µg/hr around the
clock for 7 days.
The higher release rate of Ocusert® Pilo 40 is achieved by making its rate controlling
membrane thinner & by the use of flux enhancer di 2-ethylhexyl)phthalate
Disadvantages – patient discomfort, risk of loss of insert from eye, removal of system
from the eye
2.Contact lens
Therapeutic soft lenses are often used to aid corneal wound in patients with infection,
corneal ulcers, characterized by marked thinning of cornea.
The residence time of drugs using presoaked lenses is not significantly prolonged.
Most of the drug released in first 30 minutes from presoaked contact lens.
The supply of oxygen to the eye tissues & the build up of harmful metabolite such as CO2
complications also arises during use of presoaked contact lens.
With this approach the release of the drug is significantly prolonged to many hours
compared to presoaked lenses as well the problem of concentration of preservative is
eliminated, since the drug is added without any preservative
3.Ocufit
It was designed to fit the shape and size of the human conjunctival fornix
When placed in the upper fornix of volunteers, placebo devices were retained for 2
weeks or more in 70% of the cases
21. E
nlist the evaluation parameters for ODDS
1.Thickness of film
2. Content uniformity
3. Uniformity of Weight
9. Compatibility study
The principle transport mechanism across mammalian skin is by passive diffusion. The
factors influencing and having differences in transdermal permeability of the stratum
corneum.
•Lipid solubility
At higher concentrations, the rate of penetration of the alcohols is greatly increased, and
does not follow the pattern of absorption from weak solution.
But, high concentrations may damage the stratum corneum impairing its 'barrier'
properties.
•Partition coefficient
Drugs possessing both water and lipid solubility are favorably absorbed through the skin.
Transdermal permeability coefficient shows a linear dependency on partition coefficient.
A lipid/water partition of 1 or greater is generally required for optimal transdermal
permeability.
•pH condition
The extent of dissociation in case of ionic drugs and their transdermal permeability
depends on pH condition of the skin surface as well as the drug delivery system. Incase of
ephedrine and scopolamine, the transdermal flux of the drug increases with increasing pH
upto 1.2 approximately 1.2 higher than their respective pKa values.
•Permeation Enhancers
These are compounds which promote skin permeability by altering the skin as a barrier
to the flux of a desired penetrant.These may conveniently be classified below:
23. D
iscuss different types of TDDS. (4M)
Ans:
•Multi-layer Drug-in-Adhesive
The Multi-layer Drug-in-Adhesive is similar to the Singlelayer Drug-in-Adhesive in that the
drug is incorporated directly into the adhesive.
However, the multi-layer encompasses either the addition of a membrane between two
distinct drug-in-adhesive layers or the addition of multiple drug-in-adhesive layers under a
single backing film.
•Drug Reservoir-in-Adhesive
The Reservoirtransdermal system design is
characterized by the inclusion of a liquid compartment containing a drug
solution or suspension separated from the release liner by a semi-permeable
membrane and adhesive.
The adhesive component of the product responsible for skin adhesion can either
be incorporated as a continuous layer between the membrane and the release
liner or in a concentric configuration around the membrane.
•Drug Matrix-in-Adhesive
The Matrix system design is characterized by the inclusion of a semisolid matrix containing a
drug solution or suspension which is in direct contact with the release liner.
The component responsible for skin adhesion is incorporated in an overlay and forms a
concentric configuration around the semisolid matrix.
24. G
ive the advantages of TDDS. (2M)
Ans:
a. Liposomes
Ans:
microscopic vesicles : one or more concentric lipid bilayers, separated by water or aqueous
buffer.
diameter : 25-100μm.
Small Unilamellar Vesicles (SUV) (10-100 nm)
Large Unilamellar Vesicles (LUV) (100-3000 nm).
More than one bilayers Multilamellar Vesicles (MLV).
Different methods:
1. film hydration technique
2. ether injection method
3. reverse phase evaporation method
4. membrane extrusion technique
All routes and can be used as carrier for all drugs
Example of liposome:
Duxorubicin
Use : Blood cancer
b. M
icroemulsions
Ans:
c. Nanoparticles :
Ans:
Particulate dispersions or solid particles.
Size in the range of 10-1000nm.
Dissolved, entrapped, encapsulated or attached to a nanoparticle matrix.
Drug is confined to a cavity surrounded by a unique polymer membrane.
Matrix systems.
Coated :hydrophilic polymer such as polyethylene glycol(PEG) .
long-circulating particles
Prepared by three methods :
(1)dispersion of preformed polymers;
(2)polymerization of monomers; and
(3)ionic gelation or co-acervation of hydrophilic polymers
Use :potential drug delivery devices because of their ability to circulate for a prolonged period
time in systemic circulation. Example of Nanoparticles:
Real natural product, without chemical, composed only of small particles suspended in pure
water.
Use : natural substance with antibiotic properties, antibacterial, antiviral, antifungal and
anti-inflammatory.
a particular organ.