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Solubility of poorly soluble drugs by using solid ppt

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1. Solubility of poorly soluble drugs by using solid dispersion technique Presented by Mr.Jagadeesh tekkali B.Pharmacy 11AC1R0076 VIGNAN INSTITUTE OF PHARMACEUTICAL…
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  • 1. Solubility of poorly soluble drugs by using solid dispersion technique Presented by Mr.Jagadeesh tekkali B.Pharmacy 11AC1R0076 VIGNAN INSTITUTE OF PHARMACEUTICAL TECHNOLOGY,DUVVADA
  • 2. Introduction: poorly soluble drugs like glibenclamide is an ant diabetic drug under the canary of sulphanyl urea 2.genration with is act by the potassium sensitive ATP channel by regulate insulin release from b-cell of pancreas glibenclamide is a potent drug having longer biological half life such as 10hours. So it leads toxicity to body blood. In order to seed bioacgical half improve the solubillty increase the biciavllabillty which is safest drug during pregnancy. Which class it drug Pearly water soluble drug under BCS class2 drug that means’ high permeability low solubility. Increase bioavailability of poor water soluble drugs e.g.: bcs class 2 drugs like glibenclamide/glyburide by using SD methods. Recent development in novel drug delivery systems such as SD technology. In that solid product consisting of at least two different components generally a hydrophobic drug can be incorporated into hydrophilic drug carrier. To form a SD (solid dispersion) by using different technique. Carrier should be crystalline or amorphous.
  • 3. Which is the simplest, advantageous oral bioavailability of a drug depends on it solubility and dissolution of drugs therefore efforts to increase dissolution of drugs. In formulation of poorly soluble drugs some hydrophilic carriers and super disintegrating agents such as PEG 2000,4000,6000. Etc and sodium starch glycolate(premesol), cross linked sodium CMC HPMC.added to enhance the disintegration and their by abosorption and bioavailability. In a SD technology and NDDS aims to improve safety and formulated into convential dosage forms increase patient compliance. These dosage forms dissolve or disintegrate rapidly in the oral cavity with in a matter of seconds without the need of water.SD method dissolution can be improved by increase the surface area and thereby reducing the particle size.
  • 4. Types of solid dispersions:  Simple eutectic mixtures  Solid solutions  Glass solutions  Amorphous precipitation in a crystalline carrier Simple eutectic mixtures: when a solution/mixture contain two components such as A,B which is placed in solution “S”.solution can be rapid cooling then A,B components such are crystalline out to form very fine crystals when a mixture with composition”S”. Poorly soluble drug and inert water soluble carrier (PEG, PPO, and PEO).so carrier contact with aqueous media and larger surface area resulting more dissolution rate and improved bioavailability. carrier Drug carrier Solid dispersion drug . Solid solutions: in a solid solution the two components crystallize together in homogeneous mono phasic system. The particle size of drug in the solid solution is reduced to it molecular size. So which achieve faster dissolutions rate? Which is classified into two? Continuous solid solutions Discontinuous solid solutions Classification of solid dispersion systems
  • 5. Continuous solid solutions: in a mixture/solution contain two components are formed/completed miscible with each to form solid mass.intraction B/W two components are more grater then individual components. Discontinuous solid solutions: in a mixture contain two components are limited miscibility or partially with each other to form solid mass. In that interactions B/W two components are lower than individual components atom interactions indusial components atom interactions .due to higher interactions individual components equal paten of solubility until critical temperature reached. Glass solutions and suspensions: a glass solution is a homogenous; glass system in which a solute dissolves in glass solvents .glass solvents is a pure chemical or a mixture of chemical in a glassy. The glassy is usually obtained by an abrupt quenching of the melt. It is characterized by transparency and on heating, brittleness below the “glass transition temperature” (Tg) on heating, it soften progressively and continuously without a sharp melting point. Amorphous solid solution: in that polymer carriers are particularly likely to form amorphous solid solutions as other polymer itself often present in the form of an amorphous polymer chain network in the in additions, the solute molecules may serve to plasticize the polymer, leading to a reduction in its glass transition temperatur
  • 6. Selection of carriers: the selection of hydrophilic carriers. Should have some ideal qualities such as Readily soluble in water and GI fluids Physiological inert Melting point not much higher than of the drug Relatively low vapor pressure They should be non toxic “Carrier/matrix is melted at elevated temperature and the drug is dissolved. In molten carriers .surface active agents are substance at low concentration adsorb on to the surface. First generation carriers Example: Crystalline carriers: Urea, Sugars, and and Organic acids Second generation carriers Example: Fully synthetic polymers include providence (PVP), polyethylene glycols (PEG) and polymethacrylates. Natural product based polymers are mainly composed be cellulose derivatives, such as hydroxypropylmethylcellulose(HPMC), hydroxypropylcellulose or starch derivates, like cyclodextrins. Third generation carriers Example: Surface active self emulsifying carriers:Poloxamer 408,Tween80, and Gelucire 44/14[12] carrier Carrier(hydrophilic) Substances/drugs(hydrophobic), PEG Griseofulvin, PVP Flufenamic acid,HPMC Albendazole,benipine ,Poloxamer188 Enteric polymer aspirin ,Urea Ofloxacin Sorbitol Predinisolon Types of carrier
  • 7. Advantages of solid dispersion techniques:  Particles with reduced particle size: molecular dispersions as a solid dispersion and represent the last state on particle size reduction and after inert carrier drug incorporated into it their by increase the surface area in order to increase dissolution rate and bioavailability.  Particles with higher porosity: particles in solid dispersion have been found to have a high degree of porosity and increase in porosity also depending properties of carrier molecules. If polymer having linear structure is utilized more pare in solid dispersion. So high dissolution rate.  Particles with improved wet ability: if solid dispersion carrier which is hydrophilic so more aqueous content their by more wet ability and improve the dissolutions Drug in amorphous state: if a drug poorly water soluble crystalline drugs when in the amorphous state tend to have higher degree of solubility drug in its amorphous state shows higher drug release because no energy is required to break up the crystal lattice during thedissolution process.  Metastable Forms Formation of metastable dispersions with reduced lattice energy would result in faster dissolution rates. It was found that the activation energies for dissolution for furosemide was 17 K Cal per mol, whereas that for 1:2 furosemide: PVP co precipitate was only 7.3 K Cal per mol. To obtain a homogeneous distribution of a small amount of drug in solid state.)To stabilize the unstable drugs.  To dispense liquid or gaseous compounds in a solid dosage. To formulate a fast release primary dose in a sustained release dosage form
  • 8. Disadvantages of Solid Dispersion The major disadvantages of solid dispersion are related to their instability. Several systems have shown changes in crystallinity and a decrease in dissolution rate with aging. The crystallization of ritonavir from the supersaturated solution in a solid dispersion system was responsible for the withdrawal of the ritonavir capsule (Norvir, Abboft) from the market.Moisture and temperature have more of a deteriorating effect on solid dispersions than onphysical mixtures. Some solid dispersion may not lend them to easy handling because of tackiness
  • 9. CHARACTERIZATION OF SOLID DISPERSION Many methods are available that can contribute information regarding the physical nature of solid dispersion system. A combination of two or more methods is required to study its •Thermal analysis. •Spectroscopic method. •X-ray diffraction method. •Dissolution rate method. •Microscopic method. •Thermodynamic method. •Modulated temperature differential scanning calorimetry •Environmental scanning electron microscopy •Dissolution testing.
  • 10. Method of preparation of solid dispersion: a. Kneading technique: in this method carrier is permeated with water and transformed to paste drug is then added and kneaded for particular time. The kneaded mixture is then dried and passed. Through sieve if necessary. b. Solvent evaporation method: in this method both drug and carrier are dissolved in organic solvent after entire dissolution, the solvent is evaporated. The solid mass is ground, sieved and dried. c. Co-precipitation method: required amount of drug is added to the solution of carrier. The system is kept under magnetic agitation and protected from the light the formed precipitate is separated by vacuum filtration and dried at room temperature. d. Melting method/fusion method: drug and carrier are mixed using motor and pestle to accomplish a homogenous dispersion the mixture is heated at or above the melting point of all components. It is then cooled to acquire congealed mass. It is crushed and sieved.
  • 11. e. Lyophillization technique: freeze-drying involves transfer of heat and mass to and form the product under preparation this technique. Where the drug and carrier are co dissolved in a common solvent, frozen. And sublimed to obtain a lyophilized molecular dispersion. f. Melt agglomeration process: this technique has been used to prepare SD. Where the binder act as a carrier ,drug and recipients are heated to temperature above the melting point of the binder (melt-in procedure) by spraying a dispersion of drug in molten binder on the heated incipient (spray-on-procedure)by using a higher shear mixture. g. Spray-drying method: drug is dissolved in suitable solvent and the required amount of carrier is dissolved in water. Solution is mixed by sonication/other suitable method to produce a clear solution. Which is then spray dried using spray dryer. h. Electro spinning method: in this method polymer industry combines solid solution methods with nana technology. In this procedure a liquid stream of drug/polymer solution is subjected to a potential 5 to 30 KV. When electrical force prevail over in the surface tension of the drug /polymer solution at the air interface, evaporates can be screened
  • 12. •Biopharmaceuticals and pharmacokinetics at reatise-D.M.brahmankar, sunil B.jaiswal, page no: 335 to 363. •Ansel’s pharmaceutical dosage forms and drug delivery systems.8th education loydvallen. jn, Nicholas.g.popovich, howard.c.ansel, page no:600-610. Forster, A., Hempenstall, J., Rades, T., 2001. Characterization of glass solutions of poorly water-soluble drugs produced by melt extrusion with hydrophilic amorphous polymers. J. Pharm. Pharmacol. 53,303–315. •Handbook of Pharmaceutical Excipients, third ed. The PharmaceuticalPress, London, pp. 143–145. •Advances in controlled and noval drug delivery edited by N.K jain,page no 1 to 18. •The theory and practice of industrial pharmacy , special Indian edition 2009-leon lachman, Herbert.a.liberman ,page no 174 to 180,365 to 373. •Biopharmaceuticals and pharmacokinetics-venkateswarlu. Page no 36 to 38. •Biopharmaceuticals and clinical pharmaco kinetics-milo gibaidi,4th edition ,page no 36,57,62,80. Broman, E., Khoo, C., Taylor, L.S., 2001. A comparison of alternative polymer excipients and processing methods for making solid dispersions of a poorly water-soluble drug. Int. J. Pharm. 222, 139– 151. References
  • 13. •Dordunoo, S.K., Ford, J.L., Rubinstein, M.H., 1991. Preformulation studies on solid dispersions containing triamterene or temazepam in polyethylene glycols or Gelucire 44/14 for liquid filling of hard gelatin capsules. Drug Dev. Ind. Pharm. 17, 1685–1713. •Davis, S.N., Granner, D.K., 1996. Insulin, oral hypoglycemic agents and the pharmacology of endocrine pancreas. In: Gilman, A.G. (Ed.), The Pharmacological Basis of Therapeutics, ninth ed. McGraw-Hill, NewYork, pp. 1487–1518.
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