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WELCOME

Aseminar onSOLID DISPERSION: SOLUBILITY ENHANCEMENT TECHNIQUE FOR POORLY WATER SOLUBLE DRUGS

Miss. Duduskar Anita Ankush. By Under the Guidance ofDr. Pawar P.K.Head of Department Pharmaceutics Gourishankar Institute of Pharmaceutical Education & Research Limb, Satara. (2015-16)

ContentsSolubilityIntroduction of solid dispersionDefinition & needSelection of the carrierTypes of solid DispersionPreparation TechniquesCharacterizationAdvantages of solid dispersionDisadvantages of solid dispersionApplication of solid dispersionConclusion Future ProspectsReferences

Solubility

Advantages -Increased bioavailability -Fast absorption -Patient compliance

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IntroductionThe concept of solid dispersion was originally proposed by Sekiguchi & obi.Increasing the dissolution, absorption & therapeutic efficacy of drugs in dosage forms.Increasing solubility in water.Improving the oral absorption and bioavailability of BCS Class II drugs.

Definition & NeedDefinition: The technology is the science of dispersing one or more active ingredients in an inert matrix in the solid stage.Need of solid dispersion: Increases Oral bioavailability of a drugIncreased dissolution rate.Enhanced release of drugs from ointment.Improved the solubility & stability.

Selection of A CarrierFreely water-soluble.

Non-toxic and pharmacologically inert.

Soluble in a variety of solvents.

Chemically compatible with drugs.

Types of solid Dispersion

Preparation TechniquesMelting methodSolvent methodMelting solvent method (melt evaporation)Melt extrusion methodLyophilisation TechniqueMelt Agglomeration ProcessThe use of surfactantSuper Critical Fluid (SCF) TechnologyCo-precipitation methodGel-entrapment methodKneading method

1) Melting method: Physical mixture of a drug & water soluble carrier

directly until it meltedcooled & solidified rapidly-ice bath-vigorous stirring.solid mass was crushed, pulverized & sieved.

2) Solvent evaporation method: Drug + matrix ( both dissolve in solvent) solution

evaporate the solvent solid mass is sieved & dried

Solid dispersion Example- E.g E.g..Atrovastatin + Neem gumTemperatures used for solvent evaporation generally lie in the range 23-65C. The solvent evaporation can be done by spray drying or freeze drying.

Drug dissolve in suitable solvent

Add melt of polyethylene glycol evaporation of solvent Clear suitable film left

Film dried to constant weight

Example- Paracetamol+PEG4000/PEG 6000/methyl cellulose3) Melting solvent method:

High rotating speed Drug + carrier mix at m.p small period of time using co-rotating twin- screw extruder.

Simultaneously melted & homogenized

extruded and shaped as tablets, granules, pellets

4)Melt extrusion method:

5) Lyophilisation TechniqueThe drug and carrier are co dissolved in a common solvent, frozen and sublimed to obtain a lyophilized molecular dispersion.

6) Super Critical Fluid (SCF) TechnologyThe SCF process involves the spraying of the solution composed of the solute and of the organic solvent into a continuous supercritical phase flowing concurrently.

7) Spray dryingRapid drying and specific characteristics such as particle size and shape of the final productIt is 30-50 times less expensive than freeze-drying.The process allows production of fine, dust free powder as well as agglomerated one to precise specifications.

Schematic representation of the bioavailability enhancement of a poorly water-soluble drug by solid dispersion compared with conventional tablet

Phase Separation A Kinetic Process with a Thermodynamic Cause

-Phase separation can be induced by external physical stress or the supersaturation state of the drug in the polymer

-The fundamental cause of phase separation irrespective of the stimulus is the thermodynamic instability of the formulation.

-A phase separated systems has, in its simplest form, domains of the two pure components.

-Phase separation in drug dispersions is more complex as the drug could be either crystalline, amorphous, and even in intermediate stages such as drug rich domains and systems containing both amorphous and crystalline drug

Characterization of solid dispersionI. Thermal Analysis i) Thermo-microscopic Methods ii) Differential thermal analysis (DTA) iii) Differential Scanning Colorimetry (DSC) II. X-ray diffraction (XRD)

III. FT-IR Spectroscopy

IV . Dissolution rate determination

V . Scanning Electron Microscopy

-Drug -carrier miscibilityHot stage microscopy, Differential scanning calorimetry, Powder X-ray diffraction, NMR 1H Spinlattice relaxation time.-Drug carrier interactionsFT-IR spectroscopy, Raman spectroscopy, Solid state NMR.-Physical StructureScanning electron microscopy, Surface area analysis Surface properties, Dynamic vapor sorptionInverse gas chromatography, Atomic force microscopy Raman microscopy.-Amorphous contentPolarized light optical microscopy, Hot stage microscopy Humidity stage microscopy, DSC (MTDSC)ITC, Powder X-ray diffraction.-StabilityHumidity studies, Isothermal Calorimetry DSC (Tg, Temperature recrystallization, Dynamic vaporsorption Saturated solubility studies.

Dissolution enhancementDissolution, Intrinsic dissolution Dynamic solubility, Dissolution in bio-relevant media.Powder X-ray diffractionPowder X-ray diffraction can be used to qualitatively detect material with long range order. Sharperdiffraction peaks indicate more crystalline materialInfrared spectroscopy (IR)Infrared spectroscopy (IR) can be used to detect the variation in the energy distribution of interactionsbetween drug and matrix. Sharp vibrational bands indicate crystallinity. Fourier Transformed InfraredSpectroscopy (FTIR) was used to accurately detect crystallinity ranging from 1 to 99% in purematerial.Dissolution calorimetryDissolution calorimetry measures the energy of dissolution, which is dependent on the crystallinity ofthe sample. Usually, dissolution of crystalline material is endothermic, whereas dissolution ofamorphous material is exothermic.

ApplicationsTo increase the solubility, dissolution rate , absorption and bioavailability.

Improved the solubility & stability.

To formulate a fast released dosage form.

To reduce side effect of certain drugs.

Masking of unpleasant taste and smell of drugs

Improvement of drug release from ointment, creams .

AdvantagesTo reduced particle size. To improve wettability. To improve porosity of drug. To decrease the crystalline structure of drug in to amorphous form. To improve dissolution in water of a poorly water-soluble drug.

DisadvantagesInstability

Not easy handling because of tackiness.

The scale up of manufacturing processes.

Future ProspectsDevelop new method of preparation.Development of controlled release preparation.Identification of newer carrier.Identification of vehicle or excipient that retard or prevent crystallization.

References

Singh, S., Singh,R., Yadav, L., 2011.A review on solid dispersion. International Journal of pharmacy & life sciences,1079-1090.Nikghalb ,A., Singh,G., Kahkeshan K,2012. Solid Dispersion : Method and polymers to increase the solubility of poorly water soluble drugs. Journal of Applied Pharmaceutical Science,171-172.Rodde,M., Divase,G., Devkar B., 2014. Solubility and Bioavailability Enhancement of Poorly Aqueous Soluble Atorvastatin: In Vitro, Ex Vivo, and In Vivo Studies. BioMed Research International.3-5.