EXPERIMENT NO:06

TO PREPARE AND EVALUATE MULTIPLE EMULSION .
1. AIM: To prepare and evaluate multiple emulsion. 2. REFERENCES: 1. www.Aaps.pharm sci,2003,5(1),article 7 2. Multiple emulsion :Technology & application by Abraham Aserin. 3. www.wikipedia.com 4. Remington:the science & practice of pharmacy volume-1 ;326 5. Pak.J.pharm sci,vol 21,no.4 october 2008,pp 430-437 6. Bull chem..soc. ethiop .2010,24(1)1-10 3. MATERIALS: NAME OF THE DRUG Salicylic acid Excipients Span 80 Dextrose Tween 80 COMPANY’S NAME Aghadi Industrial Estate COMPANY’S NAME Aghadi industrial Estate

4. THEORY

Introduction Spherical crystallization is a particle design technique, by which crystallization and agglomeration can be carried out simultaneously in one step and which has been successfully utilized for improvement of flowability, compactability and bioavailability of crystalline drugs. General methods of spherical crystallization are spherical agglomeration, emulsion solvent diffusion and ammonia diffusion method. The principle steps involved in the process of spherical crystallization are flocculation zone, zero growth zone, fast growth zone and constant size zone. Factors controlling the process of agglomeration are solubility profile, mode and intensity of agitation, temperature of the system and residence time. Spherical crystallization is having wide applications in pharmaceuticals like improvement of flowability and compressibility of poorly compressible drugs, masking bitter taste of drugs and improving the solubility and dissolution rate of poorly soluble drug.

Parul Institute of Pharmacy

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Electrical conductivity tests. stabilityof multiple emulsion. Half life Protein binding metabolism Renal excretion Tmax CmaX VALUE 600mg Anti inflammatory. 3. 2. FORMULA:- SR NO.8 ml 60 ml q. pH determination.s. 6. Microscopic Test.5. salicylic glucuronides and gentisic acid.02gm 30 ml 1. Type of emulsions. 2 of 15 Parul Institute of Pharmacy . DRUG PROFILE PARAMETER dose category BCS classification solubility Ionization constant bioavailability Steady state conc. 2hr 1. salicyluric acid.2 g/100 mL H2O (20 °C).rubefacient.84 M.19 M. Chloroform 0.65 M . ethanol 1. 6 Centrifuge tests. 4. 2. 1 2 3 4 INGREDIENTS FOR W/O : 1ST PHASE: light liquid paraffin oil purified water span -80 Dextrose FOR W/O/W: 2ND PHASE: purified water tween -80 w/o emulsion Blood red color QUANTITY TAKEN 30 ml 15 ml 6 ml 0. A.2 mcg/l 7.5 hrs 50-80% Salicylic acid is metabolized 80% in liver excreted mainly by the kidney as salicylic acid. 1 2 3 B. 7. Globule size.keratolytic Class I Poorly soluble in water 0. 5. methanol 2.97 at 25Ċ After oral administration 80-100% will be absorbed in stomach and in the small intestine 2-4. EVALUATION PARAMETER 1.

oil phase consisting of paraffin oil and Span 80 . particle size. primary emulsion was added to the aqueous phase containing hydrophilic surfactant (Tween 80) while agitating for 10 min. Aqueous phase was added to the oil phase drop by drop . PROCEDURE:- 1. 2. FLOW PROPERTY Flow property of the material depends on the force developed between the particle. Emulsion was then homogenized at 800 rpm for 5 min and further at 500 rpm for 5 min more. particle Parul Institute of Pharmacy 3 of 15 . Aqueous phase consisting of salicylic acid and dextrose was also heated to the same temperature. Preparation of W/O/W emulsion: Agitation was continued until cooling to room temperature of 25 oC.was heated to 55. For obtaining the multiple emulsion. Evaluation Parameters: EVALAUTION OF SPHERICAL CRYSTALS As these spherical agglomerated crystals showing significant effect on the formulation and manufacturing of pharmaceutical dosage forms so it is necessary to evalaute them by using different parametrs. Preparation of W/O emulsion: For preparation of primary emulsion . 2.8. (15 min stirr under mechanical stirrer).

DENSITY Density of the spherical crystals is the mass per unit volume.com 5 POROSITY Porosity of granules affects the compressibility. Values for angle of repose ≤ 30 usually indicate free flowing material and angle ≥ 40 suggested a poor flowing material.size distribution. the angle of repose of agglomerated crystals was 31.This improvement in the flowability of agglomerates could be attributed to the significant reduction in inter-particle friction. Porosities are of two types “intragranular and intergranular and these are measured with the help of true and granular densities. Flowability of the agglomerates is much improved as the agglomerate exhibits lower angle of repose then that of single crystals. Density = M/V Publication Ref No. surface texture or roughness and surface area. The angle of repose is the angle between the horizontal and the slop of the heap or cone of solid dropped from some elevation.25 indicate good flow (20% Carr Index) and the value greater then 1. Parul Institute of Pharmacy 4 of 15 .height of the cone and d.25 indicates poor flow ( 33% Carr Index).5d Where h.: IJPRD/2010/PUB/ARTI/VOV-1/ISSUE-12/FEB/005 ISSN 0974 – 9446 International Journal of Pharma Research and Development – Online www. The value below 15% indicates good flow characteristics and value above 25% indicate poor flowability HAUSNER RATIO It is calculated from bulk density and tap density. Hausner ratio = Tapped density / Bulk density Values less than 1. due to their spherical shape and a lower static electric charge Following are the methods used to determine of flow property ANGLE OF REPOSE This is the common method used for determination of flow property.ijprd. particle shape.diameter of the cone COMPRESSIBILITY OR CARR INDEX A simple indication of ease with which a material can be induced to flow is given by application of compressibility index I = (1-V/Vo) *100 Where v = the volume occupied by a sample of powder after being subjected to a standardized tapping procedure and Vo = the volume before tapping.Granular density /True density. The angle of repose can be obtained from equation Tan θ = h/0.12. Intragranular porosity = 1.13 while that of unagglomerated crystals was 47. Studies on spherically agglomerated aspirin crystals revealed that.

.. ρf.ρo) ...) and a... It is suggest that the surface are freshly prepared by fracture during compression of agglomerates... b. The packability of agglomerates improved compared with those of the original crystals and that the agglomerated crystals are adaptable to direct tabletting..... Spherical agglomerates possess superior strength characteristics in comparison to conventional crystals.Intergranular porosity = 1.Bulk density/ True density PACKABILITY: Improve packability has been reported for agglomerates prepared by spherical crystallization......1/b.resulting in a lower compression force required for compressing the agglomerates under plastic deformation compared to that of single crystals..I C = (Vo-Vn)/Vo...ρn= (ρf. N =Number of tapping C =Difference in volume (degree of volume reduction.. The following equation gives the intercept obtained by extrapolating the straight portion of the plots A=1n [1/(1-D0)]+B Where: Parul Institute of Pharmacy 5 of 15 ...... The packability assessed by analysis of the tapping process with the Kawakita(I) and Kuno(II) method and using the parameters a. which enhances the plastic inter particle bonding.. shear cohesive stress and shear indexes are lower then that of single crystals.. Compaction behaviour of agglomerated crystals were evaluated by using following parameters Heckel Analysis The following Heckel's equation used to analyze the compression process of agglomerated crystals and assessed their comapctibility. (-kn)…………………………II Where....... In [1/(1-D)]=KP+A Where: D is the relative density of the tablets under compression Pressure K is the slope of the straight portion of the Heckel Plot The reciprocal of K is the mean yield is the mean yield pressure (Py). The compaction behavior of agglomerated crystals and single crystals is obtained by plotting the relative volume against the compression pressure...... b are constant. which can improve the packability of the agglomerates.... The angle of friction.. exp.. COMPRESSION BEHAVIOUR ANALYSIS Good compactibility and compressibility are essential properties of directly compressible crystals. k in the equation N/C = 1/ (ab) +N/a...... a =(Vo-V∞) /Vo....Bulk density / Granular density Total Porosity = 1.

MECHANICAL STRENGTH Spherical crystals should posses’ good mechanical strength as that directly reflects the mechanical strength of compact or tablet. and assessed relaxation behavior. calculated the parameters As and Bs. the upper punch held in the same position for 20 min. The plunger acted as movable plates and set directly on the granules positioned on the lower platen as the rate of loading may affect crushing load (gm). then used the universal tensile compression tester to compress the samples at a constant speed. A window cut into the barrel to facilitate placement of granule on the base platen. t/Y(t)=1/AsBs-t/As Y(t)=(P0-Pt)/P0 Where: P0 is the maximum compression pressure. It is determine by using the following two methods. and Pt is the pressure at time t. After the certain limit of pressure attained. Tensile strength: Tensile strength of spherical crystals is measured by applying maximum load required to crush the spherical crystal. The following equation gives the relative densities corresponding to A and B. This method is a direct method to measure the tensile strength of spherical crystals Crushing Strength It is measured by using 50ml glass hypodermic syringe.D0 is the relative density of the powder bed when P=0. The hallow plunger with open end served as load cell in which mercury could be added. during which measured time for the reduction amount of the stress applied on the upper punch. The barrel is then used as hallow support and the guide tube with close fitting tolerances to the Plunger. The following equation finds the relationship between relaxation ratio Y(t) and time t.com 6 In this test put specific quantity of spherical agglomerated crystals sample in a die specific diameter the surface of which is coated with magnesium stearate in advance. Mercury is introduced from reservoir into the upper chamber at Parul Institute of Pharmacy 6 of 15 .: IJPRD/2010/PUB/ARTI/VOV-1/ISSUE-12/FEB/005 ISSN 0974 – 9446 International Journal of Pharma Research and Development – Online www. DA=1-e-A DB=DA-D0 Stress Relaxation Test Publication Ref No. The modification includes the removal of the tip of the syringe barrel and the top end of the plunger.ijprd. The result corrected by subtracting from this measurement the relaxation measured without powder in the die under the same conditions.

PARTICLE SIZE AND SIZE DISTRIBUTION Size of the particle and their distributions can be determined by simply sieve analysis.ijprd. The observations are made under the observation like 10X. In advance technology image-analyzer is used to determined size and volume of the particle. 45X. The total weight of the plunger and the mercury required to fracture a granule is the crushing load.com 7 MOISTURE UPTAKE STUDY The study indicates the behavior of uptake of moisture by drug and the prepared spherical crystals. Electron Scanning Microscopy The surface topography. The gain in weight of drug and spherical crystals is measured PARTICLE SHAPE / SURFACE TOPOGRAPHY Following methods are used Optical Microscopy The shape of the spherical crystals is studied by observing these under a optical microscope. type of crystals (polymorphism and crystal habit) of the spherical crystals is analyzed by using scanning electron microscopy. Granules along with the plastic balls placed on a test screen. Now with the help of Ro-Tap sieve shaker. The weight of powder passing through the sieve is recorded as function of time.the rate of 10 gm/sec until the single granule crushed. The friability index is determined from the slop of the plot of % weight of granules remaining on the sieve as a function of time of shaking.: IJPRD/2010/PUB/ARTI/VOV-1/ISSUE-12/FEB/005 ISSN 0974 – 9446 International Journal of Pharma Research and Development – Online www. Publication Ref No. The sieve is then subjected to the usual motion of a test sieve shaker provided the necessary attrition on the granules. Friability of agglomerates determined by using formula Friability(X) = {1-W/Wo}/100 Where Wo = Initial weight of the crystalline agglomerates placed in sieve W = Weight of the material which does not passed through sieve after 5 min. The weighted quantity of drug and spherical crystals placed in crucible at accelerated condition of temperature and humidity. FRIABILITY TEST The friability of the spherical crystals is the combination of the attrition and sieving process in to a single operation.40 C ± 10C and 75% ± 3%respectively. particle size analysis can be determined. loading time should be <3 minutes. X-ray Powder Diffraction Parul Institute of Pharmacy 7 of 15 . 60X etc. which affect the stability.

1 oC (in refrigerator). The tests were performed on samples kept at 4 ± 0.1oC. liquefaction and phase separation).3 Globules size In this study. globule sizes of the multiple emulsions prepared were determined using light Microscope fitted with a digital camera for the freshly prepared emulsions and for the emulsions kept at different conditions for 28 days . i. color. 2. The X-ray scattered in a reproducible pattern of peak intensities at distinct angle (2θ) relative to the incident beam. pH measurements were repeated for multiple emulsions after 28 days of preparation.6 Stability tests Stability tests were performed at different storage conditions for both primary and multiple emulsions. Organoleptic characteristics of both primary and multiple emulsions kept at different storage conditions. SUMMARY AND CONCLUSION The spherical 2.e. 2.2 Types of emulsions Types of emulsions were analyzed by dilution with paraffin oil and water separately and observation under microscope. 2. liquefaction and phase separation were noted at various intervals. The form of crystal in agglomerates determine by using technique. Each diffraction pattern is characteristics of a specific crystalline lattice for a compound. 25 ± 0. A drop of immersion oil was placed on the cover slide and observed under the microscope. Parul Institute of Pharmacy 8 of 15 . A drop of multiple emulsion was placed on the glass slide. An amorphous form does not produce a pattern. 2. Freshly prepared primary and multiple emulsions were investigated organoleptically (color.1 Organoleptic characteristics . 2.4 pH determination The pH value of the freshly prepared emulsions and the emulsions kept at different conditions were determined by a digital pH-meter.This is an important technique for establishing batch-to-batch reproducibility of a crystalline form.5 Microscopic tests Multiple emulsions were analyzed under the microscope to confirm the multiple characters. diluted with water and covered by a glass cover.

Taken 2ml from above and diluted up to 20ml which produced 100µg/ml.6 Dye test Water soluble dye was dissolved in the aq. water.8 In vitro release of drug In vitro release studies from O/W/O emulsions were conducted using Franz diffusion cell (at room temperature) and UV spectrophotometry.phase of an emulsion while an oil soluble dye taken up by the oil phase .2.4. at 203nm.2. taken suitable aliquot like.9 Assay of salicylic acid Calibration curve: It was prepared by taking 100 mg salicylic acid then dissolved in 100ml dis. then 1ml was taken & diluted to 10ml which produced 10 ug/ml. 2. 2.which help ful in determination of type of emulsion.6ml.8 & 10 µg/ml respectively and measured the absorbance by U.4ml.2ml.6.V. Plot the graph of Abs v/s Conc and find out the calibration curve equation. Calibration curve of Aspirin 3 OBSERVATION & CALCULATION Parul Institute of Pharmacy 9 of 15 . The results showed that in the first four-hour period.8ml and 10ml dilute up to 10ml which produce concentrations.

4 pH determination pH of freshly prepared emulsion was 4.5 12.of gobules(n) 15 35 25 20 5 ∑n=100 nd 37.5 Microscopic tests Here multiple emulsion type was o/w/o observed as follow.5 262. (3) This conforms formation of w/o/w emulsion.diameter(d) 2.2 Type of multiple emulsion COLOUR milky white Milky white Milky white LIQUEFACTION No change No change No change PHASE SEPARATION Not observed Not observed Slightly seperation (1) Microscopic evaluation shows continuous pink color through out the water phase.5 ∑nd=1075 Avg. Diameter = ∑nd/∑n = 1075/100 = 10. Parul Institute of Pharmacy 10 of 15 .5 No.1 Organoleptic characteristics Organoleptic characteristics of the primary and multiple emulsions formulated are Table presented in TIME 0hr 1hr 24hr After 1month 3. (2) We can find out no. of globules of w/o emulsion of various size moving in the continuous water phase. 3.5 7.3 Globules size Sr.5 17.No 1 2 3 4 5 Size range 0-5 6-10 11-15 16-20 21-25 Avg.8 observed.5 312.5 350 112. 3.3.75 µm 3.5 22.

at 25 °C at room temp..3. 4 °c 3.which indicated the w/o/w type of emulsion.6 Stability tests In this work. Samples were observed . i. The samples kept at different storage conditions were observed for a period of 1 month.no 1 2 3 parameter Room temperature Temp. Parul Institute of Pharmacy 11 of 15 . both primary and w/o/w multiple emulsions were divided into two samples separately and these samples were kept at different storage conditions.e. separation. at 4 °C in refrigerator. Sr.7 Dye test Microscopic examination had seen that a water soluble dye had been taken up by continous phase & the inner particles present in globules.

234 0.3.359 0.NO 1 PARAMETER ORGANOLEPTIC CHARACTERS (a)COLOUR RESULT (a)milky white CONCLUSION Parul Institute of Pharmacy 12 of 15 .585 10.8 In vitro release of drug Sr No.159 0.9 Assay of salicylic acid Calibration curve Sr No.288 0. 1 2 3 Time (hr) 1 2 3 Absorbance(nm) 0.470 0. 1 2 3 4 5 Cocentration ((ug/ml) 2 4 6 8 10 Absorbance(nm) 0. RESULT AND CONCLUSION SR.178 0.293 3.

568 0.500 10.65 % Dissolution Profile: Parul Institute of Pharmacy 13 of 15 .D.D.05 8.22 5.11 F3 (1:1) 34.05 93.8 w/o/w w/o/w 10.28 % F4 (1:0.5) 4.29 5.0 ± 0. 8.5) 4.450 0.555 Hardness ± S.70° 0.5) 33. 1 2 3 4 5 Parameter Angle of Repose Bulk Density (g/ml) Tapped Density (g/ml) Carr’s Index (%) Hausner’s Ratio (%) F1 (1:1) 30.47 % F3 (1:1) 2.0 ± 0.75µm 4.21 Thickness (mm) ± S.39 4. 10.16 1.746 25.05 8.5 ± 0.0 ± 0.968 8.10 0.5) 35.682 7.700 10.30 % Weight Variation (maximum 3. 4.05 Diameter (mm) ) ± S.05 91.0 ± 0.0 ± 0.16 F2 (1:0.43 0.98 0.33 F4 (1:0.86 1. No.8 ± 0.26 ± 0.05 Drug Content (%) 95. RESULTS AND DISCUSSION Table-1 Blend Evaluation Sr.0 ± 0. No 1 2 3 4 5 6 Parameter F1 (1:1) F2 (1:0.97 % Deviation) Friability (%) 0.7 ± 0.31 Table-2 Tablet Evaluation Sr.0 ± 0.466 14.05 97.95° 0.2 3 4 5 6 7 (b)LIQUEFACTION (c)PHASE SEPARATION TYPES OF EMULSION AVG.559 0.400 0.0 ± 0.746 23.65 0.00 1.06 1.59 0.GLOBULE SIZE PH DETERMINATION MICROSCOPIC TEST STABILITY TEST DYE TEST (b)not observed (c)observed after week w/o/w 10.D.05 8.

00 20.5 Time (Hr) HPMC 1:1 4 6 8 HPMC 1:0.00 60.00 30.00 0.00 80.5 Parul Institute of Pharmacy 14 of 15 .00 50.00 70.00 0 EC 1:1 Aspirin SR Matrix Tab % Drug Release 2 EC 1:0.90.00 10.00 40.

The swelling index study indicates that as the concentration of HPMC increases the swelling of the system is increased.Table.33 46.67 40.00 F4 25.06 25.33 66.94 48.61 58. And both the systems observed a sudden decrease in the weight after 5th hour indicates the disintegrations or erosion of the matrix.67 60.5) the evaluation is done both in the blend and the prepared tablets.0 3.33 23.3 Swelling Index: Time (Hr) 0. CONCLUSION Aspirin sustained release tablets are prepared using two different rate controlling polymers.0 6.5 1.0 2.67 63.00 63.33 56.81 41.00 43.33 63.39 51.06 58. All the evaluation tests are found to be fall with in the range of standards specified in the pharmacopoeia.33 30.0 4.67 50. The dissolution study conducted for all the formulations show the sufficient slow down of the release of the drug achieving the desired target.33 30.81 11.67 66.00 46.33 26.0 5. Ethyl cellulose and HPMC with the drug: polymer ratio (1: 1and 1: 0. Parul Institute of Pharmacy 15 of 15 .33 63.0 80 % Swelling Index 70 60 50 40 30 20 10 0 0 1 2 F1 3 Time (hr) F2 4 F3 5 F4 6 % Swelling Index F1 26.00 53.67 63.67 % Swelling Index F2 F3 23.

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