Pankaj PPT.pptx
- 2. MALARIA Malaria, a very fatal disease, it have killed millions of people over 30 years caused by the parasites termed as Plasmodium. Out of the several species of this parasite the following four are a major cause of this disease: Plasmodium malariae Plasmodium ovale Plasmodium falciparum Plasmodium vivax
- 3. Malaria is transferred by the bite of female anopheles mosquito in humans which in turn produces multiple parasites into the body There are 380 known species of the anopheles mosquito all over the world out of which only 60 can cause malaria in humans Major carriers for the malarial parasite are listed below: Humans and Female anopheles mosquito
- 4. Life cycle of a malaria parasite
- 5. Currently used antimalarial drugs Class Drug Use 4-Aminoquinoline Chloroquine For non – falciparum malaria 8-Aminoquinoline Primaquine In treating P. Vivax & P. ovale Arylamino alchohol Quinine In treating extreme malaria Mannich base antifolate Sulfadoxine Used with artesunate
- 6. MORTALITY RATES DUE TO MALARIA
- 7. AN ADAPTABLE MODE OF DRUG DELIVERY SYSTEM
- 8. Nanoemulsion comes under the category of novel drug delivery systems Size typically range from 50-200 nm Nanoemulsions consist of oil molecules or droplets dispersed in a watery phase or water droplets dispersed in an oily phase depending on their method of preparation Major difference between the emulsions and nanoemulsions is that the exhibition of kinetic stability and thermodynamic unstability
- 9. Advantages of nanoemulsions Reduction of bad taste. Enhances bioavailability. Enhances the absorption rate. Increased patient compliance. Requirement of lesser energy.
- 10. Disadvantages of nanoemulsions Large quantities of surfactant and cosurfactant is required for nanoemulsion preparation. Non toxic surfactant is required for nanoemulsion preparation. The nanoemulsion stability is effected by temperature and pH.
- 11. Components of nanoemulsion Oil - Isopropyl myristate Surfactant - Tween 80 Co-surfactant - Span 80 Aqueous phase
- 12. Preparation of nanoemulsion High energy emulsification methods I. High pressure homogenization The requirement of particle size in this technique is 10-100nm. The mixture is forced through a small inlet orifice at high pressure giving extreme turbulent force resulting in the formation of extremely fine particles
- 13. II. Sonication Sonicator probe is used to provide energy. An varying electric voltage is applied containing piezoelectric qauartz crystals which expand and contract in response to the electric voltage. Cavitation is occurred by mechanical vibrations as soon as the liquid medium comes in contact of the tip of sonicator. The resultant ultrasound produces the emulsion of droplet size 0.2mm and is mainly used for laboratory purpose.
- 14. Low energy emulsification methods Phase inversion In this method a high temperature is applied to give the varying phase transitions to give a nanoemulsion Spontaneous emulsification In this method the a homogeneous mixture of oil and lipophilic surfactant is prepared in Hydrophilic surfactant phase.The organic phase is injected using a syringe in the aqueous phase with continuous magnetic stirring resulting in the formation of the o/w nanoemulsion. Finally the aqueous is removed by heating the formed nanoemulsion.
- 15. Evaluation Parameters of Nanoemulsions Interfacial Tension Viscosity Measurement pH Refractive Index Transmission Electron Microscopy
- 16. Applications of Nanoemulsions Parentral Delivery Oral Delivery Topical Delivery Ocular Delivery In cosmetics
- 18. Primaquine comes under the category of 8 aminoquinolone which has higher efficacy in treating malaria. Side effects include vomiting, heart failure, weakness,& cramps Used in combination with other drugs. The absorbtion capacity of primaquine significantly increases when a nanoemulsion of Primaquine is used. So primaquine is widely used in treating malaria as it is readily absorbed by the liver in its nanoemulsion form because it is less toxic.
- 19. AIMS & OBJECTIVES AIM “DEVELOPMENT AND EVALUATION OF LIQUID DOSAGE FORM (EMULSION) FOR PREVENTION OF RELAPSING MALARIA” Objectives: To avoid G.I. disturbances and undesirable side effects of conventional dosage form of primaquine. To increase patient compliance. To avoid first pass effect of the drug. To avoid taste masking process/cost of drug. Minimize drug dose
- 21. 1. Literature review 2. Selection of drug 3. Preformulation studies: Identification of drug sample Determination of absorption maxima (λmax) IR determination DSC STD curve preparation Selection of oils Castor oil Almond oil Clove oil Olive oil Liquid paraffin Selection of Smix ratio (Surfactant & cosurfactant) Selection of emulsion (O/W & W/O) Selection of method of preparation High energy emulsification method Low energy emulsification method Phase inversion method Spontaneous Emulsification method
- 22. 4. Formulation of nanoemulsion: Preformulation study Solubility of drugs in oils HLB Value determination Water and oil ratio optimization Construction of phase diagram Optimization of Smix ratio 5.Evaluation of nanoemulsion: Dye test Filter paper test Light Microscopy Viscosity Zeta potential pH Centrifugation Refractive index 6. Data analysis 7. Stability studies 8. Conclusion
- 23. DRUG PROFILE STRUCTURE OF PRIMAQUINE
- 24. Category of drug: Antimalarial Physical state: Solid Colour: Orange Taste: Bitter Mol. Formula: C15H21N3O Mol. Weight: 259.347 g/mol. λmax: 259 nm Solubility: Soluble in water & moderately soluble in acetone Melting point: 197-198°C Bioavailability: 96% Half life: 3-6 hrs.
- 25. OIL PROFILE Structure of the major component of castor oil
- 26. Physical state: Oil Colour: Pale Yellow Odour: Faint, mild odour Solubility: Miscible with absolute ethanol methanol chloroform & ether Boiling point: 313°C Taste: Oil tastes slightly acrid with a decidedly nauseating after-taste Density: 961kg/m3
- 27. LIST OF CHEMICALS USED S. No. Name of the chemical Name of supplier/manufacturer 1. Primaquine Gift Sample from ITL Labs, Indore 2. Tween 80 RFCL Limited, Faridabad 3. Span 80 CDH Limited, New Delhi 4. Methyl Red Solution Fischer Scientific, Mumbai 5. Castor Oil Search Creations, Ujjain 6. Sodium Alginate CDH Limited, Delhi 7. Potassium Dihydrogen orthophosphate Qualigen fine chemicals, Mumbai 8. Sodium Hydroxide CDH New Delhi
- 28. PREFORMULATION STUDIES (A) Identification of drug sample: Determination of absorption maxima (λmax at 259nm): Absorption maxima in water:
- 29. IR DETERMINATION
- 30. DSC study for drug (primaquine)
- 32. Absorbance of 10 ppm drug solution
- 33. Absorbance of 20 ppm drug solution
- 34. Absorbance of 30 ppm drug solution
- 35. Standard curve in water y = 0.3567x R² = 0.913 0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 2 0 1 2 3 4 5 6 Absorbance Cocentration Concentration V/S Absorbance
- 36. STD curve preparation in 6.8 pH PBS The plot of absorbance Vs concentration was plotted and subjected to linear regression analysis. Drug was found to obey Beer Lambert’s law in the concentration range of 5–25 Concentration (µg/ml) Absorption 5 0.313 10 0.559 15 0.717 20 0.905 25 1.107
- 37. y = 0.0387x + 0.14 R² = 0.9959 0 0.2 0.4 0.6 0.8 1 1.2 0 5 10 15 20 25 30 A B S O R P T I O N CONCENTRATION (µg/ml) Calibration curve of primaquine in 6.8 pH P.B.S
- 38. Preparation and evaluation of dummy emulsion
- 39. Low energy method was used with 70% water and 30% Oil & Smix ratio of 1:3 Tween 80: Span 80. Surfactant and co surfactant ratio 1:3 was taken with 2ml of castor oil followed by heating on a magnetic stirrer with hot plate at a particular rpm. Water drops were added by a syringe with continuous magnetic stirring for 15 minutes followed by placing this microemulsion on a sonicator till nanoemulsion is formed.
- 40. Evaluation of dummy emulsion pH, dye test and Refractive Index of dummy nanoemulsion were evaluated as: pH – 6.13 Refractive index – 1.475
- 41. Dye test
- 42. Preparation of emulsion with drug (Without vortexing)
- 43. The above procedure was repeated with varying quantities of Smix ratio and drug. pH, dye test, filter paper test of drug loaded nanoemulsion were evaluated pH was found to be 5.88 Refractive Index was found to be 1.471
- 44. (Dye test) (Filter paper test)
- 45. Nano emulsion was now prepared by vortexing, centrifugation, phase inversion, spontaneous emulsification methods with the varying quantities of Smix ratio and drug. Same evaluation procedures were followed in all the different methods accompanied by varying results. A total of 8 formulations were prepared which is depicted in the next slide.
- 48. Following evaluation results were obtained: (Dye test) (Filter paper test)
- 50. Formulation code pH Refractive Index Viscosity (cP) Zeta - Potential (mV) F1 5.37 ± 0.03 1.488 ± 0.033 39.32 ± 1.32 -5.23 ± 0.63 F2 4.84 ± 0.04 1.532 ± 0.022 38.44 ± 1.82 -2.98 ± 0.11 F3 5.28 ± 0.02 1.569 ± 0.016 37.4 ± 1.22 -2.33 ± 0.09 F4 5.23 ± 0.06 1.468 ± 0.018 42.88 ± 2.02 -3.68 ± 0.14 F5 5.94 ± 0.03 1.427 ± 0.023 42.98 ± 2.01 -4.82 ± 0.21 F6 6.02 ± 0.05 1.520 ± 0.040 40.34 ± 1.44 -3.39 ± 0.19 F7 6.08 ± 0.04 1.529 ± 0.038 41.38 ±1.34 -5.38 ± 0.23 F8 5.74 ± 0.03 1.462 ± 0.019 40.81 ± 1.33 -4.97 ± 0.13 Evaluation parameters of nanoemulsions
- 51. CONCLUSION The preparation of nanoemulsion was made by using primaquine and castor oil Batches F1 to F8 were prepared by using low energy method for preparation of stable emulsion From the results, it is clear that minimum concentration of Smix ratio is less than 2% The nanoemulsion of all the batches were evaluated for different parameters like dye test, filter paper test, light microscopy, pH (between 5 and 6.5), viscosity (between 37 to 43 cp), refractive index (between 1.450 to 1.570) & zeta potential (between -2 to -5 mv)
- 52. The results of dye test, filter paper test and light microscopy show that the emulsion is of o/w type. Stability studies were performed on formulation F3(final formulation) results for pH, viscosity and refractive index showed no appreciable change up to 3 months of accelerated stability studies.