Suspensions & Emulsions PDF

QC OF SUSPENSIONS AND EMULSIONS  Suspensions ❖It is a biphasic system. ❖Pharmaceutical suspension can be defined as a class of dispersed systems in which a finely divided solid is dispersed uniformly in a liquid dispersion medium. ❖Colloidal suspensions (< 1 micron) ❖Coarse sus...

QC OF SUSPENSIONS AND EMULSIONS  Suspensions ❖It is a biphasic system. ❖Pharmaceutical suspension can be defined as a class of dispersed systems in which a finely divided solid is dispersed uniformly in a liquid dispersion medium. ❖Colloidal suspensions (< 1 micron) ❖Coarse suspensions (>1 micron) ❖Nano suspensions (10 ng) ❖Drug in suspension exhibits a higher rate of bioavailability than other dosage forms. ❖Solution > Suspension > Capsule > Compressed Tablet > Coated tablet Prof Yasodha Janapati 2  Suspension Continuous phase (Dispersion medium) Dispersed phase 33  Flocculated suspension & Deflocculated suspension Flocculated suspension Deflocculated suspension Particles exist as loose aggregates Particles exist as separate entities Rate of sedimentation is high Rate of sedimentation low Sediment formed rapidly Sediment formed slowly Consist of loosely packed Sediment becomes very closely particles possessing a scaffolding packed as the repulsive forces structure a hard dense cake does between the particles are not form and the sedimentation overcome a hard cake is formed can easily be redispersed. which is difficult to redisperse Elegant preparation is obtained Unsightly preparation results due due to the uniform distribution to the formation of of loosely bonded flocs sedimentation Prof Yasodha Janapati 4 Prof Yasodha Janapati 5 SOME PHARMACEUTICAL SUSPENSIONS SOME MARKETED SUSPENSION ❖ Antacid oral suspensions ❖ Antibacterial oral suspension ❖ Dry powders for oral suspension (antibiotic) ❖ Analgesic oral suspension ❖ Anthelmintic oral suspension ❖ Anticonvulsant oral suspension ❖ Antifungal oral suspension ❖ Externally applied suspension eg calamine ❖ Parenteral suspension (insulin) ❖ Ophthalmic suspension Prof Yasodha Janapati 6  Excipients for Suspension Products ❖Solvents/co-solvents e.g. Aqueous Vehicle, Propylene Glycol, Glycerol ❖Wetting agents e.g. Surfactants such as sodium lauryl sulfate ❖Thickening agents/suspending agents e.g. Methylcellulose or Hydroxyethyl cellulose ❖Humectants, e.g. Propylene Glycol, Glycerol, Sorbitol ❖Anti-foaming agents e.g. Simethicone ❖Buffering agents e.g. Citrate, Gluconates, Lactates ❖Preservatives e.g. Na Benzoate, Parabens (Me, Pr and Bu), BKC ❖Anti-oxidants e.g. BHT, BHA, Ascorbic acid ❖Sweetening agents e.g. Sorbitol, Saccharin, Aspartame, Acesulfame ❖Flavouring agents e.g. Peppermint, Lemon oils, Butterscotch, etc. Prof Yasodha Janapati 7  IPQC Tests of suspensions ❖ Appearance, Colour, odour and taste ❖ pH value ❖ Clarity testing/ Particle matter Test ❖ Uniformity of the volume ❖ Viscosity ❖ Zeta potential measurement ❖ Drug content uniformity ❖ Sedimentation rate and sedimentation volume ❖ Redispersibility ❖ Sterility test (for reconstituted injection-suspension) ❖ Dissolution test Prof Yasodha Janapati 8  Appearance ❖It must appear uniform and elegant. ❖Particles of suspension should be well distributed. ❖No hard cake formation of particles Colour, odour and taste ❖Change in colour, odour and taste indicates chemical instability. ❖These properties are fundamental in orally administered preparations. ❖ colour variation often indicates poor distribution particle size. ❖Variation in taste, especially of active constituents can often be attributed to changes in particle size, crystal habit and subsequent particle dissolution. 9 Prof Yasodha Janapati  pH value ❖pH affects the stability of the product. ❖pH of the different vehicles, before mixing and after mixing are monitored and recorded ❖This measurement is based on a scale from 0 to 14. ❖Three different types of methods used in the measurement of pH ❖pH paper ❖pH meter (The pH meter offers the highest degree of accuracy and precision) Prof Yasodha Janapati 10  pH meter ❖ The potentiometric determination of pH is measuring the potential difference between two appropriate electrodes immersed in the solution to be examined. ❖ one of these electrodes (indicator electrode) is sensitive to hydrogen ions (usually a glass electrode) and ❖ The other is the reference electrode (e.g. a silver-silver chloride electrode) ❖ Immerse the electrodes in the solution under examination and measure the pH at 25 ± 2o C ❖ pH range: 4.5-7.2 Prof Yasodha Janapati 11  Particle matter Test/ Clarity Test ❖Clarity test is carried out to check the particulate matter in the sample. 1. Photo microscopic examination 2. Change in electrical resistance (Coulter counter technique) 3. Light blockage/ light obscuration method 4. Turbidimetry or nephelometry 5. Transmission electron microscopy (TEM) 6. Scanning electron microscopy (SEM) Prof Yasodha Janapati 12  Clarity testing Photo microscopic examination ❖It examines for particles size distribution and crystal habit under the microscope with camera. ❖To determine changes in the physical properties. ❖It is mainly used for distinguish between flocculated and non- flocculated particles. Method: ❖The dilution of suspension for microscopic examination should be made with supernatant external phase rather than with purified water ❖Individual particle size distributions can be accurately determined, using a photomicroscope. Prof Yasodha Janapati 13  Change in electrical resistance (Coulter counter technique) Coulter Counter (Change in electrical resistance ) – Advanced method for particle size measurement ❖Coulter Multisizer II ❖Elzone 280 PC systems A Coulter Counter Prof Yasodha Janapati 14 Coulter Counter (Electrozone Sensing method) ❖ Particles of suspension in a dilute solution is drawn through the orifice with a voltage applied across it. ❖ Now, the Voltage pulse is recorded as particles flow through the orifice. ❖ The amplitude of pulse can be related to the volume or size of the particle. ❖ The height of the voltage pulse is proportional to the volume of particle. ❖Coulter counter can count 4000 particles per second ❖It can cover a range between 0.5-100 microns. Prof Yasodha Janapati 15  Change in electrical resistance (Coulter counter technique) ❖ Coulter Counter (Electrozone Sensing method) ❖Not only measure the particle sizes but also provide ❖Particle size distribution ❖By number ❖By length ❖By surface ❖By mass (or volume) Prof Yasodha Janapati 16  TEM & SEM ❖ Transmission electron microscopy (TEM) & scanning electron microscopy (SEM) are other useful techniques for characterisation of particle size. ❖ It's a quantitative method to determine the particle size, shape and distribution. ❖ TEM has a higher resolution than SEM. ❖ The advantages of these high-resolution methods are large field depth, high magnification, and strong stereoscopic vision. ❖ Photographs taken by TEM & SEM have higher magnifications and clearer definitions than those by optical microscopy. Prof Yasodha Janapati 17  Uniformity of Volume ❖ Pour the contents of each container into calibrated volume measures completely of the appropriate size and determine the volume of the contents of the 10 containers. ❖ If this requirement is not satisfied, the test is done on 10 additional containers. ❖ The average net volume of the contents of the 20 containers is not less than the labelled amount. ❖ Shows labelled volume and percentage allowance S. No Labelled vol of % allowance container 1 ≤50 ml 91-109% of labelled vol 2 50-200 ml 97-103% of labelled vol Prof Yasodha Janapati 18  Uniformity of Content ❖Assay 10 units individually using an appropriate analytical method. ❖Carry out the assay on the amount of well-mixed material that is removed from an individual container in conditions of normal use. ❖9 of the 10 units must contain not less than 85% or more than 115 % of labeled drug content. ❖10th units may not contain less than 75% or more than 125% of labeled content. ❖If this conditions are not meet the units remaining from the 30 (20 units) must be assayed individually and none may fall outside 85 to 115 % range. Prof Yasodha Janapati 19  Viscosity ❖ Stability of a suspension is solely dependant on the sedimentation rate of dispersed phase which is dependant on the viscosity of the dispersion medium. ❖ So this test is carried out to ensure optimum viscosity of the medium, and its ability to redispersible. ❖ Viscosity is determined using Brook field viscometer. ❖ The viscosity of the dispersion medium is measured before mixing and after mixing ❖ The calculated values are compared with standard values and if any difference is found necessary corrective action is taken to get optimized viscosity. ❖ It is very important properties of : stability of flocculated suspensions Prof Yasodha Janapati 20  Brookfield viscometer ❖ A Brookfield viscometer with a heli path attachment is a useful rheological instrument for measuring the ❖ Settling behaviour and ❖ Structure of pharmaceutical suspensions or semisolid preparation Prof Yasodha Janapati 21 Dissolution Test Prof Yasodha Janapati 22  Sedimentation volume ❖A most important parameter in the evaluation stability of the suspension. ❖50 ml of suspension is poured into a 100ml measuring cylinder and sedimentation volume is measured after 1, 2, 3 and 7 days and thereafter weekly once for 12 weeks. ❖It is the ratio between the ultimate volume of sediment to the initial volume of the suspension. ❖F=Vu/Vo F = Sedimentation volume Vu=Ultimate volume of sediment Vo= Initial volume of the suspension before settling Prof Yasodha Janapati 23  Sedimentation volume ❖ F has values ranging from less than one to greater than one. ❖ The value of F can be ‘1’, when there is no sedimentation (Vu =Vo) Ideal suspension ❖ The system is in flocculated equilibrium and shows no clear supernatant on standing. ❖ When F < 1 Vu < Vo ❖ That means suspension of less sediment ❖ When F > 1 Vu > Vo (rare case) ❖ Sediment volume is greater than the original volume due to the network of flocs formed in the suspension. ❖ So, loose and fluffy sediment Prof Yasodha Janapati 24 Sedimentation volume Prof Yasodha Janapati 25  Andreasen pipette method ❖ It is used to determine the particle size distribution after Sedimentation by Andreasen pipette and hydrometer. ❖ Andreasen apparatus consists of a 550 ml cylindrical vessel containing a 10 ml pipette sealed to a ground glass stopper. ❖ Transfer the suspension into Andreasen’s vessel and place the two-way pipette and securely suspend the vessel in a constant temperature water bath.. ❖ The pipette is placed in the cylinder such that its lower tip is 20 cm below the surface of the suspension. ❖ At different time intervals 10 ml of samples are withdrawn using two-way stopcock and collected in watch-glass, evaporated and weighed. ❖ Particle diameter is calculated from stokes law. Prof Yasodha Janapati 26 Andreasen apparatus Prof Yasodha Janapati 27  Redispersibility ❖If the particles settle they should be easily redispersible by a moderate amount of shaking. ❖Redispersibility can be estimated by shaking the suspension with hands or by some mechanical device which is stimulated with the motion of the human arm. Prof Yasodha Janapati 28  Determination of Zeta potential ❖ Zeta potential is defined as the difference in potential between the surface of the tightly bound layer (shear plane) and the electro-neutral region of the solution. ❖ Zeta potential has practical application in the stability of systems containing dispersed particles since this potential governs the degree of repulsion between the adjacent similarly charged dispersed particles. suspensions, emulsions Prof Yasodha Janapati 29  Stability of Suspensions ❖ Suspensions are thermodynamically unstable systems. ❖ The different forms and stages of instability: ❖ Sedimentation, ❖ flocculation, flotation, caking, Ostwald ripening. ❖ Stability can be increased by: ❖ Micronization of particles ❖ Viscosity enhancers ❖ Dispersing agents (e.g. surfactants and peptizers) Prof Yasodha Janapati 30  IPQC Tests of Emulsion ❖ Appearance ❖ Photo microscopic examination ❖ pH value ❖ Clarity testing ❖ Viscosity ❖ Zeta potential measurement ❖ Drug content uniformity ❖ Sedimentation rate and sedimentation volume ❖ Redispersibility ❖ Dissolution Prof Yasodha Janapati 31  Identification test for Emulsions ❖By using Naked eye, it is tough to differentiate between o/w or w/o emulsions. ❖Thus, the following methods have been used to identify the type of emulsions. ❖Dye Test ❖Dilution Test ❖Electrical conductivity Test ❖Fluorescence Test. ❖Cobalt Chloride Test. Prof Yasodha Janapati 32  Dye TEST: ❖Water-soluble dye will dissolve in the aqueous phase. ❖ Oil-soluble dye will dissolve in the oil Phase Prof Yasodha Janapati 33  Dilution test: ❖Based on the solubility of external phase of emulsion. ❖O/W emulsion can be diluted with water. ❖W/O emulsion can be diluted with oil. Prof Yasodha Janapati 34  Electrical Conductivity test: ❖As we know water is good conductor of electricity whereas oil is non-conductor. ❖Therefore, continuous phase of water runs electricity more than continuous phase of oil. Prof Yasodha Janapati 35  Fluorescence test: ❖Oils give fluorescence under UV light, while water doesn’t. ❖Therefore, O/W emulsion shows spotty pattern when observed under UV. ❖while W/O emulsion fluoresces. Prof Yasodha Janapati 36