self micro emulsified drug delivery system

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Self micro emulsified drug delivery system

• Presented by
• T.SHIVAKUMAR,STEPHEN.K
• IV YEAR I SEM
• KOTTAM INSTITUTE OF PHARMACY

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WHAT IS SMEDDS

• SMEEDS is mixture of oils, surfactants, and
  cosurfactants, which are emulsified in aqueous
  media under conditions of gentle agitation of
  digestive motility that would be encountered in
  the gastro intestinal (GI) tract.

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AIM

• Most of the new drug candidates in development
  today are sparingly soluble and associated with
  poor bioavailability
• The main purpose is to prepare SMEDDS for oral
  bioavailability enhancement of a poorly water
  soluble drug

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Bio pharmaceutical classification system
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• according to bio pharmaceutical classification
  system(BCS) the classII drugs have poor
  solubility and high permeability , thus the rate
  limiting process of absorption is the drug
  dissolution step. Formulation plays the major
  role in improving the rate and extent of
  absorption of such drugs from GI tract.

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Present study

• In the present study, an attempt was made to
  enhance the solubility and in vitro dissolution
  of candesartan cilexetil byformulating it as
  SMEDDS for filling into hard gelatin capsules.

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Drug profile

• Candesartan Cilexetil a prodrug is hydrolyzed to
  candesartan during absorption from the
  gastrointestinal tract., practically insoluble in
  water.
• Category Antihypertensive Agents
• Subcategory Angiotensin II Receptor Antagonist

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Structure
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Materials

• Drug- Candesartan cilexetile-
• Oil -Miglyol 812
• Surfactants- Cremophor EL Tween 80
• Cosurfactant -Labrasol

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• The quantity of each content will be taken
  according to the pseudo ternary phase diagram
• This diagram is very essential in manipulation of
  ingredients in the formulation of SMEDDS

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CONSTRUCTION OF PSUEDO TERNARY PHASE DIAGRAMS

• The pseudoternary phase diagrams of oil,
  surfactant
• cosurfactant, and water were developed to
  optimize the
• formulation using a water titration method.
  The mixtures
• of oil and surfactantcosurfactant ratios were
  diluted with
• water in a dropwise addition. Phase diagrams
  were constructed
• in the presence of drug to obtain the optimum
  concentrations
• of oil, surfactant, and cosurfactant. SMEDDS
  form fine oil
• water emulsions upon addition to an aqueous
  media under
• gentle agitation.

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Pseudo ternary phase diagram
The gray area indicates the microemulsion region
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formulation

• Four self-microemulsifying formulations were
  prepared using mixtures of oils, surfactants, and
  cosurfactants in various proportions. The
  self-microemulsification properties, droplet
  size, and zeta potential of these formulations
  were studied upon dilution with water. The
  optimized liquid SMEDDS formulation was converted
  into free flowing powder by adsorbing onto a
  solid carrier for encapsulation.

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images of pure drug substance (left), solid
SMEDDS (right magnification
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Dissolution studies

• The dissolution characteristics of solid
  intermediates of SMEDDS filled into hard gelatin
  capsules was investigated and compared with
  liquid formulation and commercial formulation to
  ascertain the impact on self-emulsifying
  properties following conversion.

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Results

• The results indicated that solid intermediates
  showed comparable rate and extent of drug
  dissolution in a discriminating dissolution
  medium as liquid SMEDDS indicating that the
  self-emulsifying properties of SMEDDS were
  unaffected following conversion. Also, the rate
  and extent of drug dissolution for solid
  intermediates was significantly higher than
  commercial tablet formulation. The results from
  this study demonstrate the potential use of
  SMEDDS as a means of improving solubility,
  dissolution, and concomitantly the
  bioavailability. 

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Comparision of dissolution studies
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CONCLUSION

• A SMEDDS formulation of a poorly
  water-soluble drug, candesartan cilexetil was
  formulated for direct filling into hardgelatin
  capsules for oral administrationshowed faster
  rate of drug release than the marketed product in
• a discriminating dissolution media. The
  results from this study
• demonstrate the utility of SMEDDS to enhance
  solubility and
• dissolution of sparingly soluble compounds
  like candesartan
• which may result in improved therapeutic
  performance

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Advantages

• Protection of sensitive drug substances.
• The emulsion droplets will deliver the drug to GI
  mucosa in dissolved state readily accessible for
  absorption
• When a polymer is incorporated in terms of SMEDDS
  it gives prolonged release of medicament
• They are comprised of aqueous and oily components
  and therfore can accommodate both hydrophilic
  aswell as lipophylic drugs

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Disadvantages

• Chemical instabilities
• Irritates GIT
• Precipitation of the lipophilic drugs
• Physical and chemical changes in crystalline
  solid in Cryogenic grinding

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REFERENCES

• 1. Robinson JR. Introduction semi-solid
  formulations for oral drug delivery. Bull Tech
  Gattefosse. 199689113
• 2. Aungst BJ. Novel formulation strategies for
  improving oral
• bioavailability of drugs with poor membrane
  permeation or
• presystemic metabolism. J Pharm Sci.
  19938297987.
• 3. Constantinides PP. Lipid microemulsions for
  improving drug
• dissolution and oral absorption physical
  and biopharmaceutical
• aspects. Pharm Res. 199512156172.
• 4. Pouton CW. Formulation of self-emulsifying
  drug delivery systems.

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• Thank you.

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APTI

• T.siva
• APTI/ASSN-1164
• RAN
• 1166

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• 9032796522-PRASANTHI