semisolid as ndds - vinod siju

7/31/2019 Semisolid as Ndds - Vinod Siju

1/98

SEMISOLIDSAS

NOVEL DRUG DELIVERY SYSTEM

PREPARED BY:-Siju Vinod


2/98

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


3/98

Semisolid dosage forms intendedfor topical application


4/98

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.


5/98

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.


6/98


7/98

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.


8/98

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.


9/98

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)


10/98

FIGURE OF Iontophoresis:


11/98

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


12/98

TYPES OF

NOVELSEMISOLID


13/98

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.


14/98

2) CREAMS: -

a) Creams containing microspheres: -

albumin micro spheres (225 25 m)

Emulsionmethod

Vitamin A Prolongedrelease


15/98

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.


16/98

b) Lamellar faced creams: -

Liquid paraffinin wateremulsions

cetrimide

Swellingin water


17/98

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.


18/98


19/98

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.


20/98

3) GELSControlled release gels

Organogels

Extended releasegels

Amphiphilic gels

Hydrophilic gels

Non aqueous gels

Bioadhesive Gels

Thermosensitive sol-gelreversible hydrogels

Complexation gels

GEL

S


21/98

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.


22/98

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.


23/98

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.


24/98

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.


25/98

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.


26/98

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.


27/98

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.


28/98


29/98

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.


30/98

d) Amphiphilic gels: -

Solid gelator Liquid phase

Clearisotropic

sol phase60

Cooling

Gelstructure

.

Sorbitan monostearate.

Sorbitan monopalmitate.

Liquid sorbitan esters

polysorbates


31/98

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 .


32/98

e) Hydrophilic gels

Internal phase hydrophilic polymer

3D network

External phase liquid vehicle


33/98

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.


34/98

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


35/98

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.


36/98

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.


37/98

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-


38/98

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


39/98

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.


40/98


41/98

NOVEL ADVANCES

IN

SEMISOLIDAPPLICATIONS


42/98

A) NASAL


43/98

NASAL ADMINISTRATION:

Intranasal vitamin B-12 gel produced by

Schwarz Pharma

Used as dietary supplement.

Phenylephrine hydrochloride produced by Sanofi

Used as nasal decongestant


44/98

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.


45/98

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


46/98

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:


47/98

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


48/98

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


49/98

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.


50/98

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


51/98

POLYMERS USED FOR EXTENDED RELEASE OFOCCULAR SEMISOLIDS


52/98

MARKETED PRODUCTS

b) O hth l i d i i t ti


53/98

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


54/98

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


55/98

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


56/98

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


57/98

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).


58/98

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


59/98

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.


60/98

PATENTED

TECHNOLOGIES IN

SEMISOLIDS

A)DELIVERY OF MONOCLONAL ANTIBODY USING


61/98

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.


62/98

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.


63/98

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


64/98

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


65/98

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


66/98

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


67/98

In situ formation based onphysiological stimuli

A. Thermally trigged system Temperature-sensitive hydrogels are classified

into

Negatively thermosensitivePositively thermosensitive

Thermally reversible gels

Positively


68/98

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]


69/98

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.


70/98


71/98

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 ]


72/98


73/98

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



74/98

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 .



75/98

In situ formation based onchemical reactions

Following chemical reaction causegelation :

Enzymatic cross-linking,

Ionic crosslinking, Photo-initiated processes


76/98

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-


77/98

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


78/98

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


79/98

polymeric systems


80/98

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


81/98

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


82/98

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


83/98

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


84/98

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 -


85/98

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


86/98

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


87/98

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


88/98

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:


89/98

4) Determination of mucoadhesive Force:

Mucoadhesive force was the minimum weight

required to detach two vials.

5) Gel Sol-Gel transition temperature & gelling


90/98

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


91/98

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


92/98

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


93/98

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


94/98

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


95/98

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


96/98

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


97/98

Swarbrick J, Boylan J. C., Encyclopedia of Pharmaceutical Technology. Vol. 2, 1996.Marcel Deckker Inc. 2402-2456.

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.

Atmaram Pawar, R.S Gaud., Modern Dispensing Pharmacy, 2nd Edition, 214-248.

Aulton M. E., Pharmaceutics The Science of Dosage Form Design: 2nd Edition. 1995.ELBS Churchill Livingstone. 499-530

Chater S.J., Cooper and Gunn Dispensing For Pharmaceutical Students. 12th Edition.2001. CBS Publication. 192-231.


98/98

The journey of a thousand miles begins with a

single step..

semisolid as ndds - vinod siju

Documents