This action might not be possible to undo. Are you sure you want to continue?
D) DEPARTMENT OF PHARMACEUTICS
PRESENTED BY: USHASRI.K DEPTARTMENT OF PHARMACEUTICS
NALANDA COLLEGE OF PHARMACY, CHERLAPALLY, NALGONDA TOTAL NO. OF SLIDES: 36
22/12/2010 USHASRI.K, PHARMACEUTICS 1
INTRODUCTION EFFECT OF PARTICLE SIZE ON VARIOUS PHYSICOCHEMICAL PROPERTIES IMPORTANCE OF PARTICLE SIZE ANALYSIS PARTICLE SIZE DETERMINATION METHODS CONCLUSION REFERENCES
I. , I 2
Prior to the development of dosage form with a new drug candidate, it is essential that certain fundamental, physical, chemical and other derived properties have to be determined. A thorough understanding of these properties may ultimately provide a rationale for formulation design, or support the need for molecular modification.
TI S 4 . × 22/12/2010 S S I.× The preformulation investigations confirm that there are no significant barriers to the compounds development. Quantitation of physical & chemical properties that will assist in developing: Stable. effective formulation with maximum bioavailability. safe. .
P TI 5 22/12/2010 . I.× × × × × To establish the identity & physicochemical parameters. To establish its physical characteristics. . To establish its compatibility with common excipients. Providing a scientific data to support the dosage form design & evaluation of the product efficacy. To establish its kinetic rate profile. stability & bioavailability.
× × × A newly synthesized drug shows sufficient pharmacologic promise in animal models to warrant evaluation in man. . A I. When formulation and dosage form changes are required. Preformulation activities are usually performed during the preclinical stage although those may extend to phase and . P A A I / / 0 0 .
I S 7 . 22/12/2010 S S I. . efficacious dosage form.× Study of physico chemical properties of the drug. along with excipients in order to develop a stable. safe.
PHARMACEUTICS 8 . PH solubility profile c. Dissolution 3. Thermal effects e. Bulk characterization a. Stability in toxicology formulation b. Solid state stability ± Bulk stability compatibility 22/ 2/2010 USHASRI. Crystallinity & polymorphism b.MAJOR AREAS OF PREFORMULATION RESEARCH: 1. Common ion effect Ksp d. Solution stability ± PH stability profile c. Solubility analysis a.K. Ionization constant pka b. Powder flow properties 2. Partition coefficient g. Fine particle characterization d. Hygroscopy c. Solubilization f. Stability analysis a.
Support for process development of drug substance. Helps in adjustment of pharmacokinetic and biopharmaceutical properties.× × × × × Gives direction for development of formulation in choice of drug from excipients. Produce necessary and useful data for development of analytical methods. Support for process analytical technology. . composition. physical structure. 22/12/2010 SH S I. PH I S 9 .
. a particle is defined as the smallest discrete unit. P A A U I S 10 . agglomerates etc.P. & collections of particles can be described by their degree of association such as aggregates. 22/12/2010 US AS I. A particle is any unit of matter having defined physical dimensions.× × According to U.S.
K. PHARMACEUTICS 11 .PARTICLE SIZE : 22/12/2010 USHASRI.
stability. The particle size characterstics should be evaluated to ensure the development of formulations with acceptable or reproducible bioavailability. stability. color. . flow properties. & ease of manufacture. taste. texture. content uniformity. P TI 12 . & shapes of drug & other components to be used in pharmaceutical formulations. distribution. compressibility. sedimentation rate. absorption. bioavailability. Particle size shows effect on various physical & chemical properties like drug dissolution rate. 22/12/2010 I.× × × Is to obtain quantitative data on the size.
K. solids are not static systems. Eg: Bioavailability of griseofulvin & phenacetin is directly related to the particle size distributions of these drugs. the physical state of particles can be altered by physical manipulation & particle characterstics can alter therapeutic effectiveness. PHARMACEUTICS 13 22/12/2010 . In some instances. Most drug dosage forms are solids.× × × × Particle size of drugs may affect formulation & product efficacy. particle size show effect on biopharmaceutical behavior of dosage form. USHASRI.
K.× × × × × × ON DRUG DISSOLUTION RATE MODIFIED NOYES WHITNEY EQUATION: dc/dt= DAKW/O(CS-Cb)/Vh D = Diffusion coefficient of the drug A = Surface area of the dissolving solid Kw/o = Water/oil partition coefficient of the drug considering the fact that dissolution body fluids are aqueous = Intrinsic dissolution rate constant V = Volume of dissolution medium h = Thickness of stagnant layer (Cs -Cb) = Concentration gradient for diffusion of drug S AS I. A AC TICS 14 × × × × 22/12/2010 .
I 15 .ON BIOAVAILABILITY: × ON FLOW PROPERTIES: × ON CONTENT UNIFORMITY × 22/12/2010 I. .
× Particle size measurements provide the evaluation of possible particle aggregation or crystal growth & particle size distribution data are often employed as fundamental quality control standards for pharmaceutical disperse systems. P I 1 . 22/12/2010 I. .
PHARMACEUTICS 17 .K.× × × × × × × × The various techniques involved in determination of particle size include: Optical microscopy Sieving Sedimentation rate method Coulter counter and electrical sensing devices Light scattering Hydrodynamic chromatography Laser particle size analysis 22/12/2010 USHASRI.
22/12/2010 US S I. Degree & character of aggregations. Eg. DISADVANTAGES: The diameter is obtained only from the two dimensions of the particle. UTI S 1 . Slow & tedious process.00 particles has to be counted.× × × × ADVANTAGES: Useful to obtain information about the particle shape & presence of particle aggregations. . 300 .
Uses a series of standard sieves caliberated by the NATIONAL BUREAU OF STANDARDS. 22/12/2010 US ASRI. AR A EUTI S 19 . .× It is based on either vibratory or suction principle.
DISADVANTAGES: Sieving errors can arise from number of variables.davg = × × × × (%retained)×average size/100 × × × ADVANTAGES: Simplicity both in equipment & technique.K. size reduction of granular pharmaceutical matter. It can also causes attrition & thus. can occur. Binding or clogging of screens. Large sample requirement. PHARMACEUTICS 20 22/12/2010 . USHASRI. including sieve loading & duration & intensity of agitation.
. & Hydrometer method. HA AC UTICS 21 . 22/12/2010 USHAS I. Cahn sedimentation balance method.× Several methods are there based on sedimentation rate Andreasen pipette apparatus.
Must be carefully controlled to obtain consistent & reliable results. × 22/12/2010 USHASRI. consistent sampling. Proper dispersion. PHARMACEUTICS 22 .K.× × × DISADVANTAGES: Tedious method. temperature control.
USHASRI.× × × × × It determine the number of particles in a known volume of an electrolyte solution. This type of equipment is used primarily to obtain the particle size distribution of the sample. . Electronic pulse counters are also useful in studying particle growth. HARMACEUTICS 2 22/12/2010 . The device employs the electrolyte displacement method & measures the equivalent spherical volume diameter. dv. dissolution & particulate contamination. It measures the change in an electrical sensing zone that occurs when a particle passes through an orifice positioned between two electrodes.
K.22/12/2010 USHASRI. PHARMACEUTICS 24 .
count & tabulate the individual particles that pass through sensing zone data in a short time with reasonable accuracy. × × 22/12/2010 USHASRI.× × ADVANTAGES: Both units electronically size. PHARMACEUTICS 25 . They are powerful tools & can be used for evaluation of parameters as crystal growth in suspension formulation. Thousands of particles can be counted in seconds & used to determine the size distribution curve.K.
PHARMACEUTICS 2 . is based on the principle diameter & size distribution. T. & shape of colloidal particles. × × 22/12/2010 USHASRI. Scattering may be described in terms of turbidity.× The quasi elastic light scattering technique (QUELS) also called photon correlation spectroscopy (PCS). size. Light scattering depends on the Faraday tyndall effect and is used widely in the determination of molecular weight. the fractional decrease in intensity due to scattering as the incident light passes through a solution. .
synthetic polymers. × × × × DISADVANTAGES: PCs however cannot characterize systems having broadly distributed particles.× × ADVANTAGES: When the particle is asymmetrical. association colloids & lyophobic sols. this problem has been overcome by combining sedimentation field flow fractionation & QELS. USHASRI. this method is applicable for measuring the particle size ranging from 5nm to approx 3µm. which presents a detailed record of the particle size at each size interval. permitting an estimation of the shape & size of particle light scattering has been used to study proteins. PHARMACEUTICS 27 22/12/2010 . the intensity of scattered light varies with the angle of observation.K.
22/12/2010 USHASRI.× This method is used particularly for colloids. . A colloidal dispersion is forced through a long column packed with nonporous beads with an approximate radius of 10µm. PHARMACEUTICS 2 . Particles of different particle size travel with different speeds around the beads & are thus collected in size fractions.
particles are passed through a focused laser Malvern particle size beam. These particles scatter light at analyzer 22/12/2010 USHASRI. During the laser diffraction measurement.Laser article Size Analysis consists in measuring the size of particles (powders. suspensions and emulsions) using the diffraction and diffusion of a laser beam. . HARMACEUTICS 29 .
The angular intensity of the scattered light is then measured by a series of photosensitive detectors. The map of scattering intensity versus angle is the primary source of information used to calculate the particle size.K. 22/12/2010 USHASRI.These particles scatter light at an angle that is inversely proportional to their size. PHARMACEUTICS 30 .
. HARMACEUTICS 1 .22/12/2010 USHASRI.
Pharmaceutical Preformulations and Formulations. 41-49 Gilbert S. Pharmaceutical Dosage Forms : Tablets. Mark Gibson. 533-546. Bombay. Marcell Dekker. Hoag. Modern Pharmaceutics. Banker. page no. . 22/12/2010 USHASRI. Rhodes. Augusburger. revised & expanded. page no. Libermann. Informa health care. 2008. volume 1. Third edition. 2005. Larry L. page no. fifth edition. 1991. Herbert A. 171-176.× × × × × Leon Lachman. fourth edition. Lippincott William & Wilkins publications. MARTIN S Physical Pharmacy and Pharmaceutical sciences. 2006. 273-275. The Theory And Practice of Industrial Pharmacy. PHARMACEUTICS 32 . page no. USA. Stephen W. Christopher T. Varghese publishing house.
Jr. Nicholas G. 152-174. http://tetra. 187-190. M.× × × × Loyd V. page no.E. Sunil B Jaiswal.simtech.edu. 2008.M. page no. 19.astar. Ansel. Howard C. New Delhi. Lippincott William & Wilkins publications. Churchill Livingstone.Aulton. Pharmaceutics: The Science of Dosage form and Design. D. Ansel s pharmaceutical dosage forms and drug delivery systems.sg/afbsUpload/FactSheet/ICES/Malvern%20Pa rticle%20Size%20Analyzer%20MS2000. Allen. Brahmankar.2010 22/12/2010 USHASRI. second edition. eighth edition. Vallabh prakashan. PHARMACEUTICS 33 . Biopharmaceutics And Pharmacokinetics A Treatise.12. Popovich.pdf.K.
This action might not be possible to undo. Are you sure you want to continue?
We've moved you to where you read on your other device.
Get the full title to continue reading from where you left off, or restart the preview.