semisolid as ndds - vinod siju
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SEMISOLIDSAS
NOVEL DRUG DELIVERY SYSTEM
PREPARED BY:-Siju Vinod
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INTRODUCTION Non greasy since they are made up of water washable
bases.
Nanoparticles and Microspheres: Excellent emollienteffect, with better spreadability, and less staining thanoleaginous ointments.
Preferred for dry, chapped skin in an environment oflow humidity because of its occlusive properties
Modification in gel: Release pattern and also somethermo reversible gels .
Oral Insulin delivery,
Chitosan based bioadhesive gels
TIMERx technology for controlled release,
Am hi hilic and non-a ueous els
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Semisolid dosage forms intendedfor topical application
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IDEAL PROPERTIES OF NOVELSEMISOLIDS: -
a) Novel ointment bases:
i ) should absorb more water and enhance permeation.
ii) when applied over skin, an oleaginous ointment film
should formed which prevents moisture evaporationfrom the skin.
iii) should not irritate skin.
b) Novel semisolids are safe even when applied to
inflamed skin. c) They should be odorless, easy to handle, stable
and compatible with large range of drugs and should
be safe.
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d) Use of Novel semisolids in pediatric, geriatrics
and pregnant women should be safe withoutcausing any allergic reaction.
e) Novel semisolids should able to extend the
release pattern in a controlled manner.
f) Novel semisolid should allow its use in different
routes of administration with safe, odorless, easy
to handle and compatible with biological
membrane.
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PHYSICAL MEANS1.Phonosoresis(sonophoresis):
The movement of drugs through intact skin &
underlying soft tissues under the influence of anultrasonic perturbation.
It is safe & effective technique for enhancing drug
administration in clinical applications when with a
proper frequency, power level, and duration It increases drug permeation through the skin by
disordering the structured lipids in the stratumcorneum.
Developing Transdermal drug delivery with the use ofultrasound technique(US) for effective and safe
option to treat cancerous tissue.
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Iontophoresis:
It is basically an injection without the needle.Mechanism:Repulsive electromotive force using a small
electrical charge applied to an iontophoretic chamber
containing a similarly charged active agent and itsvehicle.
The drug is applied with an electrode carrying thesame charge as the drug.
The ground electrode, which is of theopposite charge, is placed elsewhere on the bodyto complete the circuit.
The drug serves as a conductor of the
current through the tissue.
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Improve the transdermal delivery of peptideand proteins
By the process of electromigration and
electro-osmosis, iontophoresis increases thepermeation of charged and neutral
compounds like low (lidocaine) and high
molecular drugs, such as peptides (e.g.,
insulin)
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FIGURE OF Iontophoresis:
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Electrophoresis:
Here the membrane of a cell exposed to high-
intensity electric field pulses can be temporarily,thus becoming highly permeable to exogenous
molecules in the surrounding media.
The charged molecules were consideredtransporting through existing main routes of the
skin at transdermal voltage
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TYPES OF
NOVELSEMISOLID
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1) OINTMENTS: -
Rectal Ointment: Used
The symptomatic relief against anal and peri-analpruritus,
Pain and inflammation associated with hemorrhoids,
Anal fissure,
Fistulas and proctitis.
Rectal ointment should be applied several times in aday according to the severity of the condition.
For intrarectal use, apply the ointment with the helpof special applicator.
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2) CREAMS: -
a) Creams containing microspheres: -
albumin micro spheres (225 25 m)
Emulsionmethod
Vitamin A Prolongedrelease
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Albumin microsphere containing vitamin A can beadministered by using creams topically.
222 25 m size of microsphere of vitamin A were
produced by emulsion method.
The in vivo study in six volunteers revealed thatthese microspheres were able to remain on the skin
for a long period of time, and as a consequence they
were able to prolong the release of vitamin A.
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b) Lamellar faced creams: -
Liquid paraffinin wateremulsions
cetrimide
Swellingin water
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They are liquid paraffin in water emulsion prepared
from cetrimide / fatty alcohol like mixed emulsifiers
and ternary system formed by dispersing the mixedemulsifier in require quantity of water.
The cationic emulsifying wax showed phenomenal
swelling in water and this swelling was due to
electrostatic repulsion which can be suppressed by
addition of salt and can be reduced by changing
surfactant counter ion.
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It increases the penetration of topical drugs by
using oils and fats like liquid and semisolid paraffinin large quantities.
.
However, such formulations have the limitations
of poor cosmetic properties since they havegreasy feel and glossy appearance.
Nanoparticles were incorporated in the aqueous
phase. Hence, the oil phase in which the waterdroplets were dispersed served as a lubricant for
nanoparticles, thereby preventing a rough feel
during application.
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3) GELSControlled release gels
Organogels
Extended releasegels
Amphiphilic gels
Hydrophilic gels
Non aqueous gels
Bioadhesive Gels
Thermosensitive sol-gelreversible hydrogels
Complexation gels
GEL
S
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a) Controlled release gels: -
Gel formulations with suitable rheological and
mucoadhesive properties increase the contact time
at the site of absorption.
Control the release of uncharged drug substances
by including surfactants that form micelles in the gel.
The release depends on lipophilic interactions
between the drug and the polymer and/or themicelles.
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Controlled-release formulations of charged drugs
could be designed by mixing the drugs with
oppositely charged surfactants in certain fixed ratios. In this way, vesicles in which the drug and
surfactant constituted the bilayer formed
spontaneously.
The vesicle formation was affected by the presenceof polymer, and very small vesicles that gave a slow
release rate were formed when a lipophilically
modified polymer was used.
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The gels were also evaluated in the chamber
using porcine nasal mucosa and from the
results it was found that the rate of transport
of drugs through the mucosa could be
controlled by the rate of release from the
formulation. Furthermore, the chamber can be used to
evaluate the potential toxicity of formulations.
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b) Organogels:
Sorbitan monostearate, a hydrophobic nonionic
surfactant, gels a number of organic solvents suchas hexadecane, isopropyl myristate, and a range of
vegetable oils.
Gelation is achieved by dissolving/dispersing theorganogelator in hot solvent to produce an organic
solution/dispersion, which, on cooling sets to the gel
state.
Cooling the solution/dispersion causes a decreasein the solvent-gelator affinities, such that at the
gelation temperature, the surfactant molecules self-
assemble into toroidal inverse vesicles.
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Further cooling results in the conversion of the
toroids into rod-shaped tubules.
Once formed, the tubules associate with others,
and a three-dimensional network is formedwhich immobilizes the solvent.
Sorbitan monostearate gels are opaque,
thermoreversible semisolids, and they are stableat room temperature for weeks.
Such organogels are affected by the presence of
additives such as the hydrophilic surfactant,
polysorbate 20, which improves gel stability andalters the gel microstructure from a network of
individual tubules to star-shaped "clusters" of
tubules.
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Another solid monoester in the sorbitan ester
family, sorbitan monopalmitate, also gels organic
solvents to give opaque, thermoreversiblesemisolids.
Like sorbitan monostearate gels, the
microstructure of the palmitate gels comprises an
interconnected network of rod like tubules. Unlike the stearate gels, however, the addition of
small amounts of a polysorbate monoester causes
a large increase in tubular length instead of the
"clustering effect seen in stearate gels.
The sorbitan stearate and palmitate organogels
may have potential applications as delivery
vehicles for drugs and antigens.
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c) Extended release gels: -
TIMERx is a controlled release technologyconsists of an agglomerated, hydrophilic
complex that, when compressed, forms a
controlled-release matrix.
The matrix, consisting of xanthan and locust
bean gums (two polysaccharides) combined with
dextrose, surrounds a drug core.
In the presence of water, interactions betweenthe matrix components form a tight gel while the
inner core remains unwetted.
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Advantage of this system includes,
a) Predictable modified release profile like zeroorder or first order or initial immediate release
kinetics
b) It can be manufacture on standard
manufacturing equipment. c) Cheap.
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d) Amphiphilic gels: -
Solid gelator Liquid phase
Clearisotropic
sol phase60
Cooling
Gelstructure
.
Sorbitan monostearate.
Sorbitan monopalmitate.
Liquid sorbitan esters
polysorbates
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Amphiphilic gels can prepared by mixing the
solid gelator like sorbitan monostearate orsorbitan monopalmitate and the liquid phaselike liquid sorbitan esters or polysorbate andheating them at 60C to form a clear isotropic
sol phase, and cooling the sol phase to form an opaque
semisolid at room temperature.
Amphiphilic gel microstructures consistedmainly of clusters of tubules of gelatormolecules that had aggregated upon coolingof the sol phase, forming a 3D networkthroughout the continuous phase.
The els demonstrated thermoreversibilit .
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e) Hydrophilic gels
Internal phase hydrophilic polymer
3D network
External phase liquid vehicle
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It composed of the internal phase made of a polymer
producing a coherent three-dimensional net-likestructure,
which fixes the liquid vehicle as the external phase.
Intermolecular forces bind the molecules of the solvent to
a polymeric net,
Thus decreasing the mobility of these molecules and
producing a structured system with increased viscosity.
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f) Non aqueous gels: -
Ethylcellulose was formulated as a nonaqueous gel with
propylene glycol dicaprylate/dicaprate. The gel matrices exhibited prominent viscoelastic
behavior and thixotropy.
The solvent molecular conformation was found to play
a role in affecting the formation of gel networks viaintermolecular hydrogen bonding between ethyl
cellulose polymer chains
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g)Bioadhesive Gels: -
Chitosan bioadhesive gel for nasal delivery of insulin.
A nasal perfusion test was carried out to study the toxicityof four absorption enhancers like saponin, sodium
deoxycholate, ethylendiamine tetra-Acetic Acid (EDTA)
and lecithin.
The gels contained4000 IU/dl insulin,
2 or 4% of low and medium molecular weight ofchitosan,
lecithin or EDTA.
Drug release was studied by a membraneless diffusion
methodand bioadhesion by a modified tensiometry test.
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Formulations containing 2% of low molecularweight of chitosan with EDTA :
Higher release percentage , dissolution efficiency(DE)2.5%,
Lower t50% (Time required to release 50% of the
drug), mean dissolution time, and bioadhesion
Increase in insulin absorption
Reduction the glucose level by as much as 46% of
the intravenous route.
Insulin was released by a zero-order kinetic from thegels.
Use: Preparation for controlled delivery of insulin
through the nasal route.
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h) Thermosensitive sol-gel reversible hydrogels:
They are the aqueous polymeric solutions whichundergo reversible sol to gel transformation underthe influence of environmental conditions liketemperature and pH which results in insitu hydrogel
formation.Advantages of thermosensitive sol-gel reversible
hydrogels over conventional hydrogels are,
a) It is easy to mix pharmaceutical solution rather
than semisolids b) Biocompatibility with biological systems
c) Convenient to administer
d)The pharmaceutical and biomedical uses of thesuch sol-gel transition include solubilization of low-
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e) Release can be in a controlled fashion.
f) Helps to deliver labile biomacromolecule such asproteins and genes.
g) Immobilization of cells
h) And tissue engineering
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i) Complexation gels: -
The goal of oral insulin delivery devices is to protect
the sensitive drug from proteolytic degradation in the
stomach and upper portion of the small intestine.
In this work, the use of pH-responsive, poly
(methacrylic-g-ethylene glycol) hydrogels as oral
delivery vehicles for insulin were evaluated.
Insulin was loaded into polymeric microspheres and
administered orally to healthy and diabetic Wistar rats.
In the acidic environment of the stomach, the gels
were unswollen due to the formation of intermolecularpolymer complexes.
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NOVEL ADVANCES
IN
SEMISOLIDAPPLICATIONS
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A) NASAL
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NASAL ADMINISTRATION:
Intranasal vitamin B-12 gel produced by
Schwarz Pharma
Used as dietary supplement.
Phenylephrine hydrochloride produced by Sanofi
Used as nasal decongestant
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a) Introduction:
Drug delivery to nasal mucosa for either local orsystemic action faces obstacles like cilia, mucus.
These routes are protected by effective
mechanisms.
Nasal drug administration has been routinelyused for administration of drugs for the upper
respiratory tract, like adrenergic agents, and is
now also being used as a viable alternative for
the delivery of many systemic therapeutic agents.
A number of dosage forms are common and
include solutions, suspensions and gels.
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b) The advantages of nasal delivery include,
(1) Lower doses,
(2) Rapid local therapeutic effect,
(3) Rapid systemic therapeutic blood levels,
(4) rapid onset of pharmacological activity, and
(5) Few side effects.
A l f d th t h ff ti
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An example of drug that shows effectiveness upon
administration as a nasal gel, as compared to an oral
tablet, is vitamin B12, where clinical studies showed a
six fold increase in maximum blood levels, a doubling ofspeed in entering the bloodstream, and a 2.5 fold
increase in measurable vitamin B12 in the blood 48
hours after administration.
c) Risk associated with nasal semisolids:
The risk of patient-to-patient contamination is very highwith nasally administered products; patients should be
advised that a nasal product is for ONE PATIENT ONLY.
d) Formulation aspect:
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d) Formulation aspect:
In addition to the active drugs, nasal preparations
contain a number of excipients, including vehicles,buffers, preservatives, tonicity adjusting agents,
gelling agents and possibly antioxidants.
Important in the formulation process is the use of
ingredients that are nonirritating and compatible withthe nose as discussed within each category.
In general, the same excipients used in ophthalmic
formulations can also be used in nasal formulations.
B) SKIN
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B) SKIN
a) Introduction: Topical gel formulations provide a suitable delivery
system for drugs because they are less greasy and
can be easily removed from the skin.
Topical dermatologic products are intended forlocalized action on one or more layers of the skin
(e.g., sunscreens, keratolytic agents, local
anesthetics, antiseptics and anti-inflammatory
agents).
b) Ad t li ti d
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b) Advantage, application and uses:
This route of drug delivery has gained popularity
because,
(1) Provides a largest surface area
(2) It avoids first-pass effects, gastrointestinal
irritation, and metabolic degradation associated with
oral administration.
Viable epidermal or dermal sites (such as local
anesthetics or anti-inflammatory agents) may also
occasionally include a vasoconstrictor, such as
epinephrine, in the formulation to retard systemic
uptake of the drugs and, thereby, prolong its local
effect.
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C)OPHTHALMIC
a) Introduction: In ocular drug delivery, many physiological constraints
prevent a successful drug delivery to the eye due to its
protective mechanisms. Drug loss occur via,
(1)Less capacity of cualdy sac
(2)Dilution of drug due to lachrymal secretion.
(3)Nasolachrymal drainage
So formulation is administration by increasing theviscosity of dosage form in order to achieve increase in
contact time with corneal membrane. This can be
achieved by use of ophthalmic semisolids
POLYMERS USED FOR EXTENDED RELEASE OF
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POLYMERS USED FOR EXTENDED RELEASE OFOCCULAR SEMISOLIDS
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MARKETED PRODUCTS
b) O hth l i d i i t ti
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b) Ophthalmic administration: Ophthalmic semisolid compounds are useful for preventing
and treating ocular inflammation such as dry eye,
conjunctivitis, scleritis, keratitis, and uveitis.
d) Risks of ophthalmic semisolids:
Visual disturbances, including blurred vision
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e) Formulation of ophthalmic semisolids:
The ophthalmic pharmaceutical composition of the
invention includes buffers, surfactants, stabilizers,preservatives, ophthalmic wetting agents, and ophthalmic
diluting agents. Semisolid ophthalmic vehicle contain soft
petrolatum.
Absorption and water soluble bases generally are used forpreparation of ophthalmic semisolids are
Mineral oil is added to petrolatum to lower its fusion point (
but its addition increases chance of separation and to
avoid this Ozokerite, Ceresin, Micro crystalline wax in small
quantity are added.
D)RECTAL
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D)RECTAL
a) Introduction:
Rectal preparation includes Ointment, creams; gels
are used for application to perianal
area. Perianal area is the skin immediately
surrounding anus. Substance applied rectally may be absorbs by
diffusion into circulation via network of three
hemorrhoid arteries (superior inferior and middle
hemorrhoid artery).
b) Rectal administration:
Previously this route was use for bowel evacuation.
But now a days rectal route is widely use for
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NAME COMPANY API DOSGEFORM
USE
ANUSOL GlaxoSmithKline Starch Ointment hemorrhoids
TRONOLANE Ross Pramoxine
Hcl
Cream Analgesic
Antipruritic
RECTAL DELIVERY SYSTEMS
c) Advantage application and uses: several
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c) Advantage, application and uses: several
advantages of using rectal semisolids are
(1)Large surface area
(2)The ability to bypass first-pass liver metabolism,
(3)Prolongs the residence time
(4)And permeability to large molecular weight drugs,
such as peptides and proteins. (insulin gelsadministered deep rectally )
Rectal preparation are used to treat anorectal pruritis,
inflammation (hydrocortisone), discomfort with
hemorrhoids (hydrocortisone), pain (pramoxine
hydrochloride).
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d) Risks of Rectal semisolids: less frequent risk withrectal administration of drug include skin rash, dizziness,
pain, headache, abdominal pain, nervousness, diarrhea,feeling unsteady or clumsy, and wheezing
e) Formulation of Rectal semisolids:
Bases for preparation of ointment and creams are
e.g. polyethylene glycol 300,
cetyl alcohol,
cetyl ester wax,
white petrolatummineral oil.
PARENTRAL ADMINISTRATION USING ATRIGELTECHNOLOGY
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TECHNOLOGY
ADVANTAGES
Compatibility with broad range of
pharmaceutical compounds.
Direct delivery to targeted area.
Less invasive technique.
Protection of drug.
Sustained drug release.
Bio-degradable and Biocompatible.
Economical.
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PATENTED
TECHNOLOGIES IN
SEMISOLIDS
A)DELIVERY OF MONOCLONAL ANTIBODY USING
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A)DELIVERY OF MONOCLONAL ANTIBODY USING
SEMISOLID DOSAGE FORM: -
Lysostaphin was formulated into a hydrophilic cream that
forms an emulsion with the secretions of the nasal mucosa,
and aqueous formulations were made containing the
mucoadhesive polymers polystyrene sulfonate and
chitosan.
Intranasal pharmacokinetics of the drugs was measured in
mice and cotton rats.
Lysostaphin formulated in the cream increased nasalretention of the drug as compared to lysostaphin in saline
drops. Furthermore, the levels of lysostaphin in the nose
after instillation of cream are still above the minimum
bactericidal concentration for most bacterial strains.
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The results demonstrate that cream and polymerdelivery systems significantly decrease the
clearance rate of lysostaphin from the nose,
thereby enhancing their therapeutic potential for
eradicating S. aureus nasal colonization.
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B)Advances in the formulation ofsemisolid dosage forms
The formulation of a suitable semisolid dosage
form involves the selection of an appropriate
drug carrier system, with a special emphasis on
the drugs physicochemical properties andrequired therapeutic application.
Drug delivery by means of semisolid dosage
forms has seen new challenges in the past few
years in terms of altered drug-release profiles aswell as the enhanced stability of active
pharmaceutical ingredients (APIs).
IN SITU GEL DRUG
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IN SITU GEL DRUGDELIVERY
In situ is a Latin phrase which translated literally
as In position
In situ gel is drug delivery systems that are in sol
form before administration in the body, butonce administered, undergo gelation in situ,to form a gel
Administration route for in situ gel
oral, ocular, rectal, vaginal, injectable andintraperitoneal routes
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Advantages of in situ formingpolymeric delivery systems:
Ease of administration
Improved local bioavailability
Reduced dose concentration
Reduced dosing frequency,
improved patient compliance and comfort.
Its production is less complex and thus lowers the
investment and manufacturing cost.
APPROACHES OF IN SITU GEL
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APPROACHES OF IN SITU GELDRUG DELIVERY
Mechanisms used for triggering the in situ gel
formation of biomaterials
Physiological stimuli
(e.g., temperature and pH) Physical changes in biomaterials
(e.g., solvent exchange and swelling)
Chemical reactions
(e.g. enzymatic, chemical and photo-initiated
polymerization)
In situ formation based on
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In situ formation based onphysiological stimuli
A. Thermally trigged system Temperature-sensitive hydrogels are classified
into
Negatively thermosensitivePositively thermosensitive
Thermally reversible gels
Positively
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Positivelythermosensitive
A positive temperature sensitive hydrogel has anupper critical solution temperature (UCST), such
hydrogel contracts upon cooling below the UCST.
E.g. poly(acrylic acid) (PAA)
polyacrylamide ( PAAm )
polysaccharides-
[carrageenan,gellan,amylose,agarose]
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mechanism
Gelation mechanism of polysaccharides.1. At high temperatures a random coil
conformation is assumed.
2.With decreasing temperature, formation ofdouble helices that act as knots is observed.
3. The aggregation of such helices forms the
physical junctions of gels.
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Negatively thermosensitive
Negative temperature-sensitive hydrogels have alower critical solution temperature (LCST) and
contract upon heating above the LCST
E.g. . methyl cellulose
hydroxy propyl cellulose
Poly(N- isopropylacrylamide )[ PNIPAAm ]
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B. pH triggered systems
With increases external pH, Swelling of hydrogelincreases if polymer contains weakly acidic (anionic)
groups , decreases if polymer contains weakly basic
(cationic) groups.
E.g. poly ( acrylic acid) (PAA) ( Carbopol , carbomer), cellulose acetate phthalate(CAP) latex,
polymethacrilic acid(PMMA), polyethylene glycol
(PEG), pseudolatexes
In situ formation based on
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In situ formation based onphysical mechanism
Swelling : Myverol (glycerol mono- oleate ), which is polar
lipid that swells in water to form lyotropic liquidcrystalline phase structures.
It has some Bioadhesive properties and can bedegraded invivo by enzymatic action.
Diffusion : This method involves the diffusion of solvent
from polymer solution into surrounding tissueand results in precipitation or solidification ofpolymer matrix.
N-methyl pyrrolidone (NMP) has been shownto be useful solvent for such system .
In situ formation based on
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In situ formation based onchemical reactions
Following chemical reaction causegelation :
Enzymatic cross-linking,
Ionic crosslinking, Photo-initiated processes
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Ionic crosslinking
Ionic crosslinking: K- carrageenan forms rigid, brittle gels in presence
of K + .
I- carrageenan forms soft, elastic gels in presence
of Ca 2+ .
Gellan gum undergoes in situ gelling in the
presence of mono- and divalent cations , including
Ca 2+ , Mg 2+.
Alginic acid undergoes gelation in presence of
divalent/polyvalent cations .
Enzymatic cross-
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ylinking
Cationic pH-sensitive polymers containingimmobilized insulin and glucose oxidase can swell
in response to blood glucose level, releasing the
entrapped insulin in a pulsatile fashion.
Adjusting the amount of enzyme also provides aconvenient mechanism for controlling the rate of
gel formation, which allows the mixtures to be
injected before gel formation
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Photo-polymerisation
A solution of monomers or reactive macromer andinitiator can be injected into a tissue site and the
application of electromagnetic radiation used to form
gel .
long wavelength ultraviolet and visible wavelengthsare used.
Short wavelength ultraviolet is not used because it
has limited penetration of tissue and biologically
harmful .
Initiator 2,2 dimethoxy-2-phenyl acetophenone in
ultraviolet light systems Camphorquinone and ethyl
eosin in visible light systems.
Classification of In situ
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polymeric systems
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Oral-delivery:
Pectin, xyloglucan and gellan gum are usedfor in situ forming oral drug delivery systems.
An orally administered in situ gelling pectin
formulation for the sustained delivery ofparacetamol has been reported.
Main advantage of using pectin for these
formulations is that it is water soluble, so
organic solvents are not necessary in theformulation
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In situ gelling gellan formulation as vehicle for
oral delivery of theophylline is reported. The formulation consisted of gellan solution
with calcium chloride and sodium citrate
complex.
When administered orally, the calcium ions are
released in acidic environment of stomach
leading to gelation of gellan thus forming a gel
in situ
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Ocular- delivery
Polymer used :-
Gellan gum, alginic acid and xyloglucan
Drug used for Ocular in situ drug delivery:-
Antimicrobial agents and anti inflammatoryagents used to relieve intraocular tension in
glaucoma
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Conventional delivery systems often result in
poor bioavailability and therapeutic responsebecause high tear fluids turn over cause rapid
elimination of the drug from the eye .
So, to overcome bioavailability problems,
ophthalmic in situ gels were developed.
Drug release from these in situ gels is
prolonged due to longer pre-corneal contact
times of the viscous gels compared withconventional eye drops.
Nasal -drug delivery
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g ysystem:
for nasal delivery of insulin- The formulation wasin solution form at room temperature that
transformed to a gel form when kept at 37 C.
Nasal in situ drug delivery system is suitable for
protein and peptide drug delivery & braintargetted disease through nasal route.
Rectal and vaginal -
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Rectal and vaginal delivery:
xyloglucan based thermo reversible gels used
for rectal drug delivery ofindomethacin.
prolonged release vaginal gel incorporatingclotrimazole - - cyclodextrin complex was
formulated for the treatment ofvaginitis
They observe that in situ gel has broad drug
absorption peak and a longer drug residence
time as compared to commercial preparation.
Injectable-Drug Delivery
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Injectable-Drug DeliverySystems:
A novel, injectable, thermosensitive in situ
gelling hydrogel was developed for tumor
treatment.
This hydrogel consisted of drug loadedchitosan solution neutralized with -
glycerophosphate
EVALUATION OF IN SITUGEL
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GEL
1) Viscosity and rheology Measured using Brookfield rheometer or some
other type of viscometers such as Ostwald's
viscometer.
2) Clarity
The clarity of formulated solutions determined
by visual inspection under black and whitebackground.
T t l i
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3) Texture analysis
Firmness, consistency and cohesiveness of
formulation are assessed using texture analyzerwhich mainly indicates the syringeability of sol so
the formulation can be easily administered in-vivo.
Higher values of adhesiveness of gels are needed
to maintain an intimate contact with surfaces liketissues
4) Determination of mucoadhesive Force:
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4) Determination of mucoadhesive Force:
Mucoadhesive force was the minimum weight
required to detach two vials.
5) Gel Sol-Gel transition temperature & gelling
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5) Gel Sol-Gel transition temperature & gellingtime
sol-gel transition temperature may be defined as
that temperature at which the phase transition from
sol meniscus to gel meniscus is occurred.
Gel formation is indicated by a lack of movementof meniscus on tilting the tube
Gelling time is the time for first detection of gelation.
6) Gel-Strength
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6) Gel Strength
This parameter can be evaluated using a rheometer.
Method: The changes in the load on the probe can be measured
as a function of depth of immersion of the probe below
the gel surface.
7) Thermogravimetric analysis
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7) Thermogravimetric analysis
can be conducted for in situ forming polymeric
systems to quantitate the percentage of water inhydrogel.
Differential scanning calorimetry is used to observe if
there are any changes in thermograms as compared
with the pure ingredients used thus indicating theinteractions .
8) In-vitro drug release studies
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The drug release studies are carried out by using the
plastic dialysis cell which is made up of two half cells,
donor compartment and a receptor compartment . Both half cells are separated with the help of
cellulose membrane.
Sol form of formulation is placed in donor
compartment.
The assembled cell is then shaken horizontally in an
incubator.
The total volume of the receptor solution can beremoved at intervals and replaced with the fresh
media.
This receptor solution is analyzed for the drug
release using analytical technique
9) For injectable in situ gels
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The formulation is placed into vials containing
receptor media and placed on a shaker water bath at
required temperature and oscillations rate.
Samples are withdrawn periodically and analyzed
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Drug Polymer used Route ofadministration
Results
Theophylline Gellan gum Oral Four five fold increase of
bioavailability in rats and three fold
in rabbits as compared to comercial
oral formulation
Doxorubicine Human serum albuminand tartric acid
derivative
Injectable Sustained delivery of anti cancerdrug for a long period app. 100 hr.
Paracetamol and
Ambroxol
Pectin Oral Sustained oral delivery
Metoclopramidehydrochloride
Poloxamer 407 andpolyethylene glycol
Nasal Ease of administration, accuracy ofdosing, prolonged nasal residence
and improved drug bioavailability
Cinnarizine 4% of sodium alginate
with 0.5% of calcium
carbonate
Oral Formulation having sustained drug
action for 12 hours.
Drug Polymer used Route of Results
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Drug Polymer used Route ofadministration
Results
Sumatriptan Pluronic F127
(PF127) andCarbopol 934P
Nasal prolonging nasal
residence time andincrease nasal absorption
Timolol Maleate Carbopol and
Chitosan
Ocular Therapeutically
efficacious and showed a
diffusion controlled type of
release behaviour over 24h periods.
clarithromycin
and
metronidazole
benzoate
Sodium alginate
and CaCO 3
Oral Sustained oral delivery
Itraconazole
(1%w/w).
Polaxamer with
carbopol 934
oral topical gels
( mucoadhesive
buccal gel)
increase in Buccal
residence time and
patient comfort
Salbutamol
Sulphate
carbopol 934 and
HPMC
nasal sustained release and
higher bioavailability
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Lachman L, Lieberman H. A, Kanig J. L., Theory and Practice of Industrial Pharmacy.4th Indian Edition. 1991, Verghese Publishing House. 534-563.
Remington, The Science and Practice of Pharmacy. Vol. 1. 19th Edition. 1995. Mackpublishing Company. 304-310.
Martin A. Bustamante P. Chun A. H. C., Physical Pharmacy, Lippincott Williams &Wilkins. 4th Indian Edition. 2005. B. I. Publication Pvt. Ltd. 500-501.
Loyd V.Allen,Jr., Nicholas G.Popovich, Howard C. Ansel, Ansels PharmaceuticalDosage Forms and Drug Delivery Systems 8th Edition. 276-297.
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