Solid dispersion
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The document discusses solubility enhancement techniques for poorly water-soluble drugs, focusing on solid dispersion methods that increase bioavailability and dissolution rates. It details preparation techniques, characterizations, advantages, and disadvantages of solid dispersions, emphasizing the need for effective carriers. Future prospects include the development of new preparation methods and controlled-release formulations.
Solid dispersion
- 2. A seminar on : SOLUBILITY ENHANCEMENT TECHNIQUE FOR POORLY WATER SOLUBLE DRUGS Miss. Duduskar Anita Ankush. By Under the Guidance of Dr. Pawar P.K. Head of Department Pharmaceutics Gourishankar Institute of Pharmaceutical Education & Research Limb, Satara. (2015-16)
- 3. Contents Solubility Introduction of solid dispersion Definition & need Selection of the carrier Types of solid Dispersion Preparation Techniques Characterization Advantages of solid dispersion Disadvantages of solid dispersion Application of solid dispersion Conclusion Future Prospects References
- 5. Introduction The 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.
- 6. Definition & Need Definition: 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 drug Increased dissolution rate. Enhanced release of drugs from ointment. Improved the solubility & stability.
- 7. Selection of A Carrier Freely water-soluble. Non-toxic and pharmacologically inert. Soluble in a variety of solvents. Chemically compatible with drugs.
- 8. Types of solid Dispersion
- 9. Preparation Techniques Melting method Solvent method Melting solvent method (melt evaporation) Melt extrusion method Lyophilisation Technique Melt Agglomeration Process The use of surfactant Super Critical Fluid (SCF) Technology Co-precipitation method Gel-entrapment method Kneading method
- 10. 1) Melting method: Physical mixture of a drug & water soluble carrier directly until it melted cooled & solidified rapidly-ice bath-vigorous stirring. solid mass was crushed, pulverized & sieved.
- 11. 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 gum Temperatures used for solvent evaporation generally lie in the range 23-65°C. The solvent evaporation can be done by spray drying or freeze drying.
- 12. 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 cellulose 3) Melting solvent method:
- 13. 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:
- 15. 5) Lyophilisation Technique The drug and carrier are co dissolved in a common solvent, frozen and sublimed to obtain a lyophilized molecular dispersion. 6) Super Critical Fluid (SCF) Technology The 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 drying Rapid drying and specific characteristics such as particle size and shape of the final product It 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.
- 16. Schematic representation of the bioavailability enhancement of a poorly water-soluble drug by solid dispersion compared with conventional tablet
- 17. 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
- 18. Characterization of solid dispersion I. 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
- 19. -Drug -carrier miscibility Hot stage microscopy, Differential scanning calorimetry, Powder X-ray diffraction, NMR 1H Spin lattice relaxation time. -Drug carrier interactions FT-IR spectroscopy, Raman spectroscopy, Solid state NMR. -Physical Structure Scanning electron microscopy, Surface area analysis Surface properties, Dynamic vapor sorption Inverse gas chromatography, Atomic force microscopy Raman microscopy. -Amorphous content Polarized light optical microscopy, Hot stage microscopy Humidity stage microscopy, DSC (MTDSC) ITC, Powder X-ray diffraction. -Stability Humidity studies, Isothermal Calorimetry DSC (Tg, Temperature recrystallization, Dynamic vapor sorption Saturated solubility studies.
- 20. Dissolution enhancement Dissolution, Intrinsic dissolution Dynamic solubility, Dissolution in bio- relevant media. Powder X-ray diffraction Powder X-ray diffraction can be used to qualitatively detect material with long range order. Sharper diffraction peaks indicate more crystalline material Infrared spectroscopy (IR) Infrared spectroscopy (IR) can be used to detect the variation in the energy distribution of interactions between drug and matrix. Sharp vibrational bands indicate crystallinity. Fourier Transformed Infrared Spectroscopy (FTIR) was used to accurately detect crystallinity ranging from 1 to 99% in pure material. Dissolution calorimetry Dissolution calorimetry measures the energy of dissolution, which is dependent on the crystallinity of the sample. Usually, dissolution of crystalline material is endothermic, whereas dissolution of amorphous material is exothermic.
- 21. Applications To 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 .
- 22. Advantages To 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.
- 23. Disadvantages Instability Not easy handling because of tackiness. The scale up of manufacturing processes.
- 24. Future Prospects Develop new method of preparation. Development of controlled release preparation. Identification of newer carrier. Identification of vehicle or excipient that retard or prevent crystallization.
- 25. 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.