INNOVATION IN SEMISOLID DOSAGE FORM

INNOVATION IN
SEMISOLID DOSAGE
FORM
INTRODUCTION
• A recent advances in
semisolid dosage form
allows modified release as
well as flexibility in route of
administration
NOVEL SEMISOLIDS
• Novel semisolids are made up from water
washable bases so they cause less
irritation to skin and are superior to
conventional semisolid dosage form.
• Novel creams are provided with
nanoparticles and microspheres which has
an excellent emollient effect , with better
spreadibility and less staining.
• Innovations in gels in terms of
modification of release pattern
•
•
•
•
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Complex gels for insulin delivery
Chitosan based bioadhesive gels
TIMERX technology for controlled release
Amphiphilic gels
non aqueous gels
• Number of new bases for gels, ointments
and creams are developed which
facilitates the delivery of above novel
semisolids by various route like nasal
,parenteral and ophthalmic.
IDEAL PROPERTIES OF NOVEL
SEMISOLIDS
• NOVEL OINTMENT BASES
• Absorb more water and enhance
permeation
• Form film over skin which prevents
evaporation of moisture
• Not irritate skin
• Novel semisolids are safe even when
applied to inflammed skin
• They should be odorless,easy to
handle,stable and compatible with large
range of drugs
• Use of that in pediatric,geriatrics and
pregnant women should be safe.
• They should extend the release pattern in
a contrlled manner.
• They allow their use in different routes of
administration.
NOVEL ADVANCES IN
SEMISOLID DOSAGE FORM
OINTMENTS
• RECTAL OINTMENTS
• It is used for the symptomatic relief against anal and
peri anal pruritus,pain and inflammation associated
with hemorrhoids ,anal fissure,fistules and proctitis.
• Modern ointment bases
• modified london-zopf base
• carbopol
• glyceryl mono stearate
CREAMS
• CREAMS CONTAINING
MICROSPHERE
• Albumin microsphere containing vitamin A can
be administered by using cream topically.
• 200-250 micron size of microsphere of vitA were
produced by emulsion method.
• In VIVO study revealed that these microsphere
were able to remain on the skin for a long
period of time and so they prolong the release of
vit A
LAMELLAR FACED CREAMS
• They are liquid paraffin in water emulsion
prepared from cetrimide/fatty alcohol like mixed
emulsifier and ternary system formed by
dispersing the mixed emulsifier in required
quantity of water.
• The cationic emulsifying wax showed
phenomenal swelling in water due to
electrostatic repulsion which can be suppressed
by addition of salt and can be reduced by
changing surfactant counter ion.
CREAM CONTAINING LIPID
NANOPARTICLES
• Occlusion of cream is important criteria since it
increases the penetration of topical drugs.
• This can be achieved by using oils and fats like
liquid and semisolid paraffin in large quanties.
• A high degree of occlusivity was obtained with
smooth , flexible films prepared by drying
aqueous dispersion of solid parafffin particles
with a mean size of 200 nm.
• However,this nanodispersion revealed a rough
texture when applied.
• The development of a w/o cream where in
the aqueous phase was divided into small
droplets solved this problem.
• Nanoparticles were incorporated in the
aqueous phase. Hence, the oil phase in
which the water droplets were dispersed
serve as a lubricant for nanoparticles ,
thereby preventing rough feel during
application.
GELS
• CONTROLLED RELEASE GELS
• Gel formulation with suitable rheological and
mucoadhesive properties increase the
contact time at the site of absorption.
• It was possible to control the release of
uncharsed drug substances by including
surfactants that form micelles in the gels.
• The release depends on lipophilic
interactions between the drug and the
polymer and/or the micells.
• Controlled release formulation of charged drugs
could be designed by mixing the drugs with
oppsitely charsed surfactant in certain fixed
ratio.
• In this way,vesicles in which the drug and
surfactant constituted the bilayer formed
spontaneously.Vesicles formation was affected
by the presence of polymer.
• Small vesicles gave a slow release rate when a
lipophilically modified polymer was used.
ORGANOGELS
• Sorbitan monostearate, a hydrophobic
nonionic surfactant,gels a number of
organic solvents such as hexadecane
,isopropyl myristate and a range of
vegetable oils.
• Organogels have potential applications as
delivery vehicles for drugs and antigens.
PREPARATION OF ORGANOGELS
• Gelation is achieved by dissolving the
organogelator in hot solvent to produce an
organic solution which on cooling sets to
gel state.
• Cooling the solution causes the decrease
the solventgelator affinity.
• At the gelation temperature the surfantant
molecules self assemble into toroidal
inverse vesicle.
• Further cooling results in the conversion of
toroids into rod tul is bules.
• Once formed,the tubules associate with
other and 3 – dimensional network is
formed which immobilizes the solvent and
organogel is thus formed.
Extended release gel
• TIMERx is controlled release technology
consist of an agglomerated,hydrophilic
complex when compressed forms control
release matrix.
• The matrix consist of xanthan and locust
bean gums combnied with dextrose
surrounds a drug core.
• In the presence of water, interaction
between matrix components form a tight
gel while the inner core remain unwetted
• Thus, the gel matrix control the release
until the matrix erodes
• Advantages
• Predictable modified release profile like
zero order or first order.
• It can be manufacture on standard
manufacturing equipment
• cheap
Amphiphilic gels
• It can be prepared by mixing the solid
gelator like sorbitan monostearate or
sorbitan monopalmitate and the liquid
phase like polysorbat or sorbitan ester and
heating them at 60 c to form clear isotropic
solution phase and cooling the solution
phase to form opaque semi solid at room
temperature.
• It consisted mainly of clusters of tubules of
gelator molecules that had aggregated
upon cooling of the solution phase forming
At the skin surface temperature the gel
softened considerably this would allow the
topical application
Hydrophilic gel
• Hydrophilic gelsare bicoherent systems
composed of internal phase made of
polymer producing a coherent 3- d net like
structure which fixes the liquid vehicle as
the external phase.
• Inter molecular forces bind the molecules
of solvent to the polymeric net thus
decrease the mobility of this molecule and
producing a structure system with
increased viscosity
• Pharmaceutical research now concentrate
primarily on hydrophilic gels, as this
dosage form seems to be prospective for
the development of modern drugs based
on systems with prolonged and controlled
release of active ingradients
Bioadhesive gels
• Chitosan bioadhesive gel was formulated
for nasal delivery of insulin.
• The gels contained 4000 Iu/dl insulin, 2 or
4 % of low or medium mol. Weight of
chitosan and lecithin or EDTA.
• Drug release studied by membraneless
diffusion method and bioadhesion by
modified tensiometry test.
• Formulation containing 2 % of low mol.
Weight of chitosan with EDTA had higher
release percentage and dissolution
Complexation gels
• 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
• In te acidic enviornment of the stomach,
the gel remains unswollen due to
formation of intermolecular polymer
complexes. the insulin remain in the gel
and was protected from proteolytic
Thrmosensitive sol-gel
resevesible hydrogel
• They are aqueous polymeric solution
which undergo reversible sol to gel
transformation under the influence of
environmental condition like temp. and ph
which results in in situ hydrogel formation.
• Advantages
• Convenient to administer
• Release can be in controlled fashion
Novel advance in semi solid
applications
• Nasal route
Drug delivery to nasal mucosa for either
local or systemic action faces obstacles
like cilia,mucus.
advantages
lower dose
rapid local therapeutic effect
rapid systemic therapeutic blood level
• Uses
• In addition to nasal decongesatants, saline
and other routine locally acting
drugs,nasal administration is being
investigated for the delivery of
insulin,vaccines, no. of polypeptides and
proteins.
• E.g. vit. B12 nasal gel increase the six fold
blood level than vit B12 tablets.
Opthalamic
• In occular drug delivery many
physiological consraints prevent the
succesful drug delivery to eye. Drug loss
occur
• 1) less capacity of cualdy sac
• 2)dilution of drug due to lachrymal
secretion
• 3)nasolachrymal drainage
• So formulation administrated by increasing
the viscosity of dosage form.
• Uses
• Wide range of eye ointment available in
market.
• E.g. acyclovir eye ointment
•
chloramphenicol ophthalmic ointment
Formulation
Ophthamlic pharmaceutical composition
including
buffers,surfcantant,stabiliser,preservatives
,ophthalmic wetting agent and ophthamlic
diluting agent
Rectal route
• It includes ointment,cream,gel for
application to perianal area.
• Advantages
• Large surface area
• By pass First pass hepatic metabolism
• Prolong residence time
• Permeability to large mol. Weight drugs
such as peptide and protiens.
• Insulin gel administrated deep rectally
Marketed formulation
• Anusol (starch)
• Tronolan (pramoxin hcl)
References
• Swarbrick J,Boylan J.C,Encyclopedia of
pharmaceutical Technology, Vol. 14,
1996.Marcel Deckker Inc. 31 – 59
• Lachman L,Libberman H.A,Kanig
J.L,Theroy and practice of Industrial
pharmacy. 4th edition. 1991, Verghese
Publishing House. 534 – 563
• Remington, The science and practice of
pharmacy. Vol. 1 .19th edition. 1995. 304 310
• Euro. J. pharma. Biopharma Vol. 50. No.1
July 3.2000. 27 – 46
• Banker G.S.,Rhodes C.T., Modern
Pharmaceutics. Vol.7. 1979. Marcel
Deckker 272 - 276
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