Microspheres and microcapsules

This is having formulation and evaluation of Microspheres and Microcapsules.

1. Microspheres and Microcapsules Prepared by . Jay Bhavsar M.Pharm (Pharmaceutics) Sem-2 Roll No. MU006 Guided by . Dinal Patel (Assistant Professor) Department of Pharmaceutics Faculty of Pharmacy, DDU, Nadiad 1

2. Mono or multinuclear materials embedded in spherical coating matrix are called microspheres. Microspheres are small spherical particles, with diameters 1 μ m to 1000 μ m. Mono or multinuclear materials enclosed by a coat or membrane are called as microcapsules. which are biodegradable in nature and ideally having a particle size less than 200 μm . Microspheres Microcapsules 2

3. Microspheres: The ability to incorporate reasonably high concentrations of the drug. Stability of the preparation after synthesis with a clinically acceptable shelf life. Controlled particle size and dispersability in aqueous vehicles for injection. Release of active reagent with a good control over a wide time scale. Biocompatibility with a controllable biodegradability. Susceptibility to chemical modification. Ideal Characteristics 3

4. Particle size reduction for enhancing solubility of the poorly soluble drug. P rovide constant and prolonged therapeutic effect. P rovide constant drug concentration in blood there by increasing patient compliance Decrease dose and toxicity. Protect the drug from enzymatic and photolytic cleavage hence found to be best for drug delivery of protein. Better drug utilization will improve the bioavailability and reduce the incidence or intensity of adverse effects. Advantages of Microspheres: 4

5. The costs of the materials and processing of the controlled release preparation, are substantially higher than those of standard formulations. The destruction of polymer matrix and its effect on the environment. Reproducibility is less. Process conditions like change in temperature, pH, solvent addition, and evaporation/agitation may influence the stability of core particles to be encapsulated. The environmental impact of the degradation products of the polymer matrix produced in response to heat, hydrolysis, oxidation, solar radiation or biological agents. Limitation: 5

6. TYPES OF MICROSPHERES: 6

7. Adhesion can be defined as sticking of drug to the membrane by using the sticking property of the water soluble polymers. Adhesion of drug delivery device to the mucosal membrane such as buccal , ocular, rectal, nasal etc. can be termed as bio adhesion. These kinds of microspheres exhibit a prolonged residence time at the site of application and causes intimate contact with the absorption site and produces better therapeutic action. 1. Bioadhesive microspheres : 7

8. This kind of delivery system is very much important which localizes the drug to the disease site. In this larger amount of freely circulating drug can be replaced by smaller amount of magnetically targeted drug. Magnetic carriers receive magnetic responses to a magnetic field from incorporated materials that are used for magnetic microspheres are chitosan, dextran etc. The different types of A) Therapeutic magnetic microspheres used to deliver chemotherapeutic agent to liver tumor. Drugs like proteins and peptides can also be targeted through this system. B) Diagnostic microspheres, used for imaging liver metastases and also can be used to distinguish bowel loops from other abdominal structures by forming nano size particles supramagnetic iron oxides. 2. Magnetic microspheres: 8

9. In floating types the bulk density is less than the gastric fluid and so remains buoyant in stomach without affecting gastric emptying rate. The drug is released slowly at the desired rate, and the system is found to be floating on gastric content and increases gastric residence. Moreover it also reduces chances of dose dumping. It produces prolonged therapeutic effect and therefore reduces dosing frequencies. Drug ( ketoprofen ) is given in the form of floating microspheres. 3. Floating microspheres: 9

10. Radio embolization therapy microspheres sized 10-30 nm are of larger than the diameter of the capillaries and gets trapped in first capillary bed when they come across. They are injected in the arteries that leads them to tumor of interest so all these conditions radioactive microspheres deliver high radiation dose to the targeted areas without damaging the normal surrounding tissues. It differs from drug delivery system, as radio activity is not released from microspheres but acts from within a radioisotope typical distance and the different kinds of radioactive microspheres are α emitters, β emitters, γ emitters. 4. Radioactive microspheres: 10

11. i ) Biodegradable polymeric microspheres: Natural polymers such as starch are used with the concept that they are biodegradable, biocompatible, and also bio adhesive in nature. Biodegradable polymers prolongs the residence time when contact with mucous membrane due to its high degree of swelling property with aqueous medium , results gel formation. The rate and extent of drug release is controlled by concentration of polymer and the release pattern in a sustained manner. The main drawback is, in clinical use drug loading efficiency of biodegradable microspheres is complex and is difficult to control the drug release. However they provide wide range of application in microsphere based treatment. 5. Polymeric microspheres: 11

12. ii) Synthetic polymeric microspheres: Synthetic polymeric microspheres are widely used in clinical application, moreover that also used as bulking agent, fillers, embolic particles, drug delivery vehicles etc. and proved to be safe and biocompatible but the main disadvantage of these kind of microspheres, are tend to migrate away from injection site and lead to potential risk, embolism and further organ damage. 5. Polymeric microspheres: 12

13. METHOD OF PREPARATION: 13

14. 1. Solvent Evaporation 14

15. 2. Single emulsion technique 15

16. 3. Double emulsion technique 16

17. 4. Phase saperation coacervation technique 17

18. 5. Spray drying and spray congealing 18

19. 6. Solvent extraction 19

20. 7. Polymerization 20

21. Microspheres polymers: 1. Synthetic Polymers: 2. Natural polymers 21

22. Microencapsulation: Microencapsulation is a process of incorporating drugs into small size multiparticulate units. This technique involve coating of surfactants are sometimes added to film coating particles ranging dimensionally from several tenth of a micrometer to about 5000 micrometer. Microencapsulation: 22

23. Fundamentals of Microencapsulation. The core material can be liquid or solid in nature. The composition of the core material can be varied as liquid core which can be include dispersed and/or dissolved material and the solid core can be diluents, recipients and release rate retardants or accelerators. The shape of core should be uniform and regular. In order to obtain uniform coating on regular microcapsules spherical particles, polymer type, shape and size core material are to be considered. The selection of a specific coating material is dependent upon under to increase segmental mobility, imparts flexibility, reduce brittleness and increase resistance of the film coating to Failure produced by mechanical stress, substances such as phthalate esters, fatty acid esters and glycol derivatives. Core Materials: Coating Materials: 23

24. Types of polymers used in the coating: Natural: Synthetic: 24

25. Microcapsules: Microcapsules are characteristically free flowing powders consisting of proteins or systemic polymers, which are biodegradable in nature and ideally having a particle size less than 200 μ m. Microcapsules of biodegradable and non-biodegradable polymers have been investigated for sustained and controlled fashion. 25

26. Microcapsules are spherical, empty particles. Microcapsules are free flowing powders consisting of proteins or synthetic polymers, which are biodegradable in nature. They have a particle size less than 200 μm . Microcapsules also act as carriers for the targeting of the anti-cancer drug to the tumor. Microcapsules incorporate reasonably high concentration of drug. Stability of the microcapsules is high. Characteristics: 26

27. Types of Microcapsules: 27

28. Mechanism of Drug Release from Microcapsules: The dissolution fluid penetrates the shell then the core comes into contact with dissolution fluid and leaks through interstitial channels or pores. The rate kinetics of drug release follows higuchi equation Q=[D/J (2A- € CS) CSt ]½ Q = Amount of drug release per unit area of exposed surface in time t. J = Tortuosity of the capillary system in the wall. D = Diffusion co-efficient of solute in solution. A = Total amount of drug per unit volume. € = Porosity of the wall of microcapsules. CS = Solubility of the drug in permeating dissolution fluid. The rate of drug release depends upon the dissolution rate of polymer coat, when coat is soluble in dissolution fluid. It also depends upon the solubility in the dissolution fluid and thickness of coat material. The release of the drug occurs by dissolution of the coat or by melting the wall of the capsule. 1. Diffusion controlled monolithic system: 2. Dissolution: 28

29. The drug is dissolved in matrix and is distributed throughout the core. The drug is attached to the matrix and is released on degradation of the matrix. The diffusion of the drug is slow when compared to degradation of the matrix. The release of the drug by erosion mechanism occurs due to pH or enzymatic hydrolysis of the coat. The physico -chemical properties of core material like solubility, diffusibility , partition co-efficient and for coating materials like thickness, porosity. The drug release from microcapsules follow zero order kinetics 3. Degradation Controlled Monolithic System: 4. Erosion: 29

30. Techniques for Preparation of Microcapsules : Air suspension coating: Coacervation process: Pan coating: Centrifugal extrusion process: : Spray drying and congealing method: Solvent evaporation method: Interfacial Polymerization: Insitu polymerization: 1 . Physical Methods 2. Chemical Methods 3. Physicochemical Methods Coacervation phase separation: Ionotropic gelation method: 30

31. 1. Air suspension coating: 31

32. Simple Coacervation: A disolvation agent is added for phase separation. Complex Coacervation: It involves complxeation between two oppositely charged polymers. 2. Coacervation process: 32

33. 3. Pan coating: 33

34. 4. Centrifugal extrusion process: 34

35. Spray drying: Aqueous solution / hot air Spray congealing: Hot melt / cold air. 5. Spray drying and congealing method: 35

36. 6. Solvent evaporation method: 36

37. 7. Polymerization: 37

38. List of micro capsulated drugs: 38 S.No Drug Polymers used Method 1. Captopril Carbopol,Chitosan Emulsion Ionic Gelation 2. Verapamil Ethyl cellulose, Cellulose Acetate Hotmelttechnique,Ionic Gelation 3. Tetracycline Ethyl Cellulose Solvent evaporation 4. 5-Flurouracil Sodium Alginate/ Chitosan Suspension crosslinking 5. Propranolol Eudragit Solvent Evaporation 6. Metoprolol Succinate SCMC, HPMC, Sodium alginate Ionic Gelation 7. Cefotaxime Ethylcellulose Solvent Evaporation 8. Diclofenac Sodium Ethylcellulose Emulsion Solvent Evaporation 9. Norfloxacin Gelatin Coacervation, Complex emulsion 10. Salbutamol SCMC,MC Ionotropic Gelation

39. EVALUATION OF MICROSPHERES & MICROCAPSULES: 39

40. 1. Particle size and shape : The most widely used procedures to visualize microparticles are conventional light microscopy (LM) and scanning electron microscopy (SEM). 2. Electron spectroscopy for chemical analysis: The surface chemistry of the microspheres can be determined using the electron spectroscopy for chemical analysis (ESCA). 3. Density determination: The density of the microspheres can be measured by using a multi volume pycnometer . 4. Isoelectric point: The micro electrophoresis is used to measure the electrophoretic mobility of microspheres from which the isoelectric point can be determined. 5. Angle of contact: The angle of contact is measured to determine the wetting property of a micro particulate carrier. 6. In vitro methods: Release studies for different type of microspheres are carried out by using different suitable dissolution media, mostly by rotating paddle apparatus (USP / BP). 7. Drug entrapment efficiency : Drug entrapment efficiency can be calculated using following equation, % Entrapment = Actual content/Theoretical content x 100. 8. Swelling index : The swelling index of the microsphere was calculated by using the formula, Swelling index= (mass of swollen microspheres – mass of dry microspheres/mass of dried microspheres) 100 . 40

41. APPLICATION OF MICROSPHERES & MICROCAPSULES: 41

42. REFERENCES: Kadam N. R. And Suvarna V, MICROSPHERES: A BRIEF REVIEW, Review Article, 20/08/2015. Krishna Sailaja A. And Jyothika M., A REVIEW ON MICROCAPSULES, Cibtech Journal Of Pharmaceutical Sciences ISSN: 2319–3891, 2015 Vol.4 . Alagusundaram.M *, Madhu Sudana Chetty.C , MICROSPHERES AS A NOVEL DRUG DELIVERY SYSYTEM- A REVIEW, International Journal Of Chemtech Research, CODEN( USA): IJCRGG ISSN : 0974-4290, Vol.1, No.3 , Pp 526-534, July- sept 2009. Azagheswari , Binil Kuriokase , Sathireddy Padma And S. Padma Priya , A Review On Microcapsules, Global Journal Of Pharmacology 9 (1): 28-39, 2015, ISSN 1992-0075 Miléna Lengyel 1, Nikolett Kállai-szabó 1, Vince Antal 1, András József Laki 2,3 And István Antal 1,* Microparticles , Microspheres , And Microcapsules For Advanced Drug Delivery, Sci. Pharm., 9 August 2019. 42