Acromegaly= too much growth hormone Periodontitis is inflammation and infection of the ligaments and bones that support the teeth
SEMINAR BY: B.THILAK CHANDRA M.PHARMACY(PHARMACEUTICS),(II-Semester)VAAGDEVI INSTITUTE OF PHARMACEUTICAL SCIENCES BOLLIKUNTA, HANAMKONDA.
CONTENTS INTRODUCTION CLASSIFICATION OF POLYMERS. METHODS OF PREPARATION. MECHANISAM OF DRUG RELEASE FROM MICROSPHERE. CHARACTERIZATION. APPLICATIONS. CONCLUSION. REFERENCES
INTRODUCTIONDefinition of microspheresMicroparticles or microspheres are defined as small spheres made of any material and sized from about 50 nm to about 2 mm.The term nanospheres is often applied to the smaller spheres (sized 10 to 500 nm) to distinguish them from larger microspheresMicrobeads and beads are used alternatively for microspheres.
Ideally, microspheres are completely spherical and homogeneous in size.
Types of MicrospheresMicrocapsule: consisting of an encapsulated core particle. Entrapped substance completely surrounded by a distinct capsule wall. Types of Microspheres Microcapsule MicromatrixMicromatrix: Consisting of homogenous dispersion of active ingredient in particle.
Polymers used in the MicrospherepreparationSynthetic PolymersNon-biodegradable PMMAAcroleinEpoxy polymersBiodegradableLactides and Glycolides copolymersPolyalkyl cyanoacrylatesPolyanhydrides
GENERAL METHODS OFPREPARATION Single Emulsion techniques Double emulsion techniques Polymerization techniques - Normal polymerization. - Interfacial polymerization Coacervation phase separation techniques Spray drying and spray congealing Solvent extraction
SIMPLE EMULSION BASED METHOD Aq.Solution/suspension of polymer Stirring, Sonication Dispersion in organic phase (Oil/Chloroform) Chemical cross linking (Glutaraldehyde/ForHeat denaturation CROSS LINKING maldehyde/ButanolMicrospheres in organic phase Microspheres in organic phase Centrifugation, Washing, Separation MICROSPHERES
DOUBLE EMULSION BASED METHOD Aq.Solution of protein/polymer Dispersion in oil/organic phase Homogenization First emulsion (W/O) Addition of aq. Solution of PVA Multiple emulsion Addition to large aq. Phase Denaturation/hardening Microspheres in solution Separation, Washing, Drying MICROSPHERES
BULK POLYMERIZATIONPolymerization with heating /initiator Mould/mechanical fragmentation
Suspension polymerizationMonomer, bioactive materials,initiator Dispersed in water Droplets Vigorous agitation Heat/ irradiation Microspheres
Emulsion polymerization Aq.solution of NaOHMonomer/ bioactive with intiator, surfactant material above cmc stabilizer Dispersion with vigorous stirring Micellar solution of polymer in aq.medium polymerization Microspheres formation Seperation, washing, drying Microspheres microspheres
Interfacial Polymerization techniqueWhen two reactive monomers are dissolved in immiscible solvents, the monomers diffuse to the oil- water interface where they react to form a polymeric membrane that envelopes dispersed phase.Drug is incorporated either by being dissolved in the polymerization medium or by adsorption onto the nanoparticles after polymerization completed.The nanoparticle suspension is then purified to remove various stabilizers and surfactants employed for polymerization by ultracentrifugation and resuspending the particles in an isotonic surfactant-free medium.
PHASE SEPARATION METHOD Aqueous/Organic.Solution of polymer Drug Drug dispersed or dissolved in polymer solution Polymer rich globules Hardening Microspheres in aq./organic phase Separation, Washing, Drying MICROSPHERES
Salting-out process An aqueous phase saturated with electrolytes (e.g., magnesium acetate, magnesium chloride) and containing PVA as a stabilizing and viscosity increasing agent is added under vigorous stirring to an acetone solution of polymer.In this system, the miscibility of both phases is prevented by the saturation of the aqueous phase with electrolytes, according to a salting-out phenomenon.The addition of the aqueous phase is continued until a phase inversion occurs and an o/w emulsion is formed
DRUG LOADINGDuring the preparation of microspheres or after the formation of microspheres by incubating.Loading into preformed microspheres has an advantage of removing all impurities from microsphere preparation before the drug is incorporated.High loading can be achieved by insitu loading.If the drug is insoluble in dispersion medium employed for microsphere stabilization.
ROUTE OF ADMINISTRATIONORAL DELIVERYPARENTERAL DELIVERY
MECHANISM OF DRUG RELEASEDegradation controlled monolithic system.Diffusion controlled monolithic system.Diffusion controlled reservoir system.Erodable polyagent system.
Characterisation METHODS PARAMETERS1. PARTICLE SIZE Light microscope, scanning electron microscope, confocal laser scanning microscopy . AND SHAPE2. CHEMICAL electron spectroscopy for chemical analysis (esca) ANALYSIS3. DEGRADATION Attenuated total reflectance Fourier Transform- OF POLYMER Infrared Spectroscopy MATRIX4. DENSITY Multivolume pychnometer DETERMINAT ION5. ISOELECTRIC Micro-electrophoresis POINT
POTENTIAL USE OF MICROSPHERESIN THE PHARMACEUTICAL INDUSTRYTaste and odour masking.Conversion of oils and other liquids to solids for ease of handling.Protection of drugs against the environment (moisture, light etc.). Separation of incompatible materials (other drugs or excipients). Improvement of flow of powders. Aid in dispersion of water-insoluble substances in aqueous media, and Production of SR, CR, and targeted medications.
OTHER APPLICATIONSMicrocapsules are also extensively used as diagnostics, for example, temperature-sensitive microcapsules for thermographic detection of tumors.In the biotechnology industry microencapsulated microbial cells are being used for the production of recombinant proteins and peptides.Encapsulation of microbial cells can also increase the cell- loading capacity and the rate of production in bioreactors.A feline breast tumor line, which was difficult to grow in conventional culture, has been successfully grown in microcapsules.Microencapsulated activated charcoal has been used for hemoperfusion.
Microspheres are made from polymeric , waxy or protective materials that is biodegradable synthetic polymers and modified natural products.Solid biodegradable microspheres incorporating a drug dispersed or dissolved throughout particle matrix have the potential for controlled release of the drug.These carriers received much attention not only for prolonged release but also for the targeting anti cancer drugs to the tumour.These Microspheres are free-flowing and roll with practically no friction, that means there is no abrasion, guaranteeing a dust-free environment.
MARKETED PRODUCTSDrug Commercial Company Technology Indication nameRisperidone RISPERDAL® Janssen®/Alker Double Schizophrenia; CONSTA® mes, Inc. emulsion (oil bipolar I in water) disorderNaltrexone Vivitrol® Alkermes Double Alcohol emulsion (oil dependence in water)Octreotide Sandostatin® Novartis Phase Acromegaly LAR separationSomatropin Nutropin® Genentech/Alk Alkermes Growth Depota ermes ProLease® deficiencies Technology (Cryogenic spray-drying)Bromocriptine Parlodel LAR Novartis Spray dry Parkinsonism ™Minocycline Arestin® Orapharma Periodontitis
CONCLUSIONThe concept of microsphere drug delivery systems offers certain advantages over the conventional drug delivery systems such as controlled and sustained delivery. Apart from that microspheres also allow drug targeting to various systems such as ocular , intranasal , oral and IV route .Novel technologies like magnetic microspheres, immunomicrospheres offer great advantages and uses than conventional technologies.
Further more in future by combining various other strategies, microspheres will find the central place in novel drug delivery, particularly in diseased cellsorting ,diagnostics, gene and genetic materials, safe,targated and effective invivo delivery which may have implications in gene therapy.This area of novel drug delivery has innumerable applications and there is a need for more research to be done in this area.
REFERENCES International Journal for Targeted & Controlled Drug Delivery Novel Carrier Systems., S.P.Vyas., R.K.Khar, First Edition :2002.,Reprint :2007 page no:417,453. Review: Radioactive Microspheres for Medical Applications. International journal of Pharmaceutics 282 (2004) 1- 18,Review polymer microspheres for controlled drug release. Controlled and novel drug delivery edited by N.K.Jain reprint 2007 pg.no.236-255. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2811640.