INNOVATION IN SEMISOLID DOSAGE FORM

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INNOVATION IN SEMISOLID DOSAGE FORM
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INTRODUCTION

• A recent advances in semisolid dosage form allows
  modified release as well as flexibility in route
  of administration

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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.

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• Innovations in gels in terms of modification of
  release pattern
• Complex gels for insulin delivery
• Chitosan based bioadhesive gels
• TIMERX technology for controlled release
• Amphiphilic gels
• non aqueous gels

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• 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.

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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

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• 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.

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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

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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

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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.

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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.

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• 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.

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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.

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• 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.

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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.

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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.

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• 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.

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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

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• 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

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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 3 d
  network throughout continuous phase

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• At the skin surface temperature the gel softened
  considerably this would allow the topical
  application

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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

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• 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

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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 efficiency and bioadhesion

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Complexation gels

• The use of ph responsive, poly (methacrylic-g-ethy
  lene 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 degradation

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Thrmosensitive sol-gelresevesible 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
• Biocompatible with biological system

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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

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• 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.

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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.

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• 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,ophth
  almic wetting agent and ophthamlic diluting agent

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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

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Marketed formulation

• Anusol (starch)
• Tronolan (pramoxin hcl)

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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

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• 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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