platform tech ion exchange resin for geriatric patient[1]

SUBJECT SEMINAR : 

SUBJECT SEMINAR Prepared by: Ajay Patel Semester-III, K.B.I.P.E.R. Guide: Dr Pragna Shelat Co Guide: Mr Punit Parejiya

SUBJECT : 

SUBJECT Platform technology suitable for geriatric patient

Content : 

Content Platform technology Preparation of sustained release oral suspension Materials Equipment Release mechanism Release profile Mathematical modelling

Platform technology : 

Platform technology OralXRTM is the platform technology of Tris Pharma Inc. for preparation of sustained release oral suspension.

Materials : 

Drug Ion exchange resin Release retardants Polymer Plasticizer Liquid carrier for suspension preparation Materials

Contd.. : 

Contd.. Drug: This technology is well suited for water soluble drug. Any acidic or basic water soluble drug bound to ion exchange resin can be used.

Contd.. : 

Ion exchange resin: Cationic or anionic exchange resin can be used depending on wether drug is weakly basic or acidic. Ion exchange resin with particle size of 50 to about 150 microns, ion exchange capacity of 3 to about 5 meq/gram and degree of cross linking of 6 to about 12% can be used. e.g., DOWEXTM50WX8H and AMBERLITETM IRP-69 are strong cationic exchange resin of choice. Contd..

Contd.. : 

Contd.. Release retardants: It forms matrix with drug-ion exchange resin complex and used to prolong drug release and reduces coating thickness required to form diffusion barrier. It should be used in the range of about 10 to about 15% by weight of the uncoated drug-ion exchange resin complex. Examples of suitable release retardants include polyvinyl acetate, cellulose acetate, ethylcellulose or acrylic acid based polymers.

Contd.. : 

Polymer: Polymer is used to provide highly flexible, substantially tack free, water insoluble but water permeable diffusion barrier and it should be about 35 to about 40% by weight of uncoated drug-ion exchange resin complex. Polyvinyl acetate polymer or a blend of polymers comprising polyvinyl acetate polymer is particularly of choice. e.g., KOLLICOAT SR 30 D contains 27% PVA, 2.7% PVP and 0.3% Sodium Lauryl Sulfate Contd..

Contd.. : 

Plasticizer: To enhance film formation and to maintain flexibility of film plasticizer can be applied. e.g., Dibutylsebacate Propylene glycol diethylphthalate Liquid carrier: Liquid carrier comprising pharmaceutical acceptable sweetners, preservatives, suspending agents, thickening agents, humectant, flavoring agent, coloring agent and opacifier can be used. Contd..

Preparation of sustained release oral suspension : 

Preparation of sustained release oral suspension Loading of drug on ion exchange resin Microencapsulation of drug-resin complex Suspending prepared microcapsule in suitable vehicle

Loading of drug on ion exchange resin : 

Loading of drug on ion exchange resin Batch method is suitable for loading of drug on ion exchange resin in which drug and ion exchange resin is stirred with purified water for required time and then supernatant is decanted. More than one equilibration stage will be required to achieve desirable loading (10 to about 40%) onto the ion exchange resin. Then wet complex is dried and release retardant is slowly added to form uniform mass in hobart type mixer.

Loading mechanism : 

Loading mechanism

Contd.. : 

Contd.. Drug ions are loaded onto resin by exchange with the sulfonic acid group protons

Equipments used for mixing : 

Equipments used for mixing HL 1400 HOBART MIXER

Microencapsulation of prepared complex : 

Microencapsulation of prepared complex A laboratory scale fluid bed processor (GPCG 2 LabSystem by Glatt Air Techniques, Inc.) is used to perform coating with bottom spray configuration.

Equipment used for coating : 

Equipment used for coating GPCG 2 LabSystem Apparatus specification

Technical data of GPCG 2 LabSystem: : 

Technical data of GPCG 2 LabSystem:

Release mechanism : 

Release mechanism In the ion-exchange process, the rate-controlling step is shown to be diffusion either in the resin particle itself, so-called particle diffusion or in an adherent stagnant film, film diffusion. Since particle diffusion and film diffusion are sequential steps, the slower of the two is rate-controlling.

Drug release in stomach : 

Drug release in stomach In the stomach the drug exchanges with H+ ions

Drug release in intestine : 

Drug release in intestine In the intestine the drug exchanges with the Na+/K+ ions of the intestinal fluid.

Release profile : 

Release profile This shows release profile of dextromethorphan- DOWEXTM50WX8H complex coated with 5%w/w KOLLICOAT SR 30 D by wurster process using fluid bed coating.

Mathematical Modelling : 

Mathematical Modelling Reichenberg’s model: The value of Bt may be plotted against the experimental value of t and if a straight line passing through the origin is obtained we can say that kinetics of drug release from the ion-exchange resin microcapsules is controlled by particle diffusion control. Where, F is the fraction of dissolution value, dp is the mean diameter of resin (mm), D is the diffusion coefficient or diffusivity (mm2/min), B is the exchange rate constant (min−1), t is time (min)

Contd.. : 

Contd.. Bhaskar model: Particle diffusion control can be extrapolated by calculating from a linear relationship between −ln(1−F) and t0.65. Where, F is the fraction of dissolution value, dp is the mean diameter of resin (mm), D is the diffusion coefficient or diffusivity (mm2/min), t is time (min)

References : 

References Ketan Mehta, U.S. Patent, 12/722,857 (2010). John.W. Keating, U.S. Patent, 2,990,332 (1961). Borodkin S. Ion exchange resin and sustained release. In: Swarbrick J, Bolan JC.editors. Encyclopedia of pharmaceutical technology vol.8. New York: Marcel Dekker;1993: p.203-16. www.trispharma.com Seong Hoon J,Nahor Haddish B,Kamyar H,Kinam P. Drug release properties of polymer coated ion-exchange resin complexes: experimental and theoretical evaluation. J Pharm Sci. 2007;96(3):618-32. Ichikawa H, Fujioka K, Adeyeya CM, Fukumori Y. Use of ion-exchange resin to prepare 100 μm-sized microcapsules with prolonged drug-release by the Wurster process. Int J Pharm 2001;216:67-76.

Contd.. : 

Contd.. Eva R, Peter D, Krista H, Andreas Z.Reformulation of a codeine phosphate liquid controlled-release product. Drug Dev Ind Pharm; 2010:1-9 Varaporn B, Greepol M. Release profile comparison and stability of diltiazem–resin microcapsules in sustained release suspensions. Int J Pharm;352 (2008): 81–91. Mohammad J. Drug loading onto ion-exchange microspheres:Modeling study and experimental verification. Biomaterials; 27 (2006): 3652–3662

Slide 27: 

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