Sustained and controlled drug delivery system

All about the drug delivery system

1. Sustained And Controlled Drug Delivery System Presented By- Mr. Bhamare Prashant Jayawant M.Pharm, Sem- II nd 1 st year DEPARTMENT OF PHARMACEUTICS R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur. 1

2. Contents Definition of SR and CRDDS Comparison of drug release profile Advantages and disadvantages of SR and CRDDS Drug selection criteria for SR and CRDDS Classification of oral SR and CRDDS Evaluation of SR and CRDDS Application of SR and CRDDS Conclusion References 2

3. Sustained drug delivery system Sustained release are drug delivery system that achieve slow release of drug over an extended period of time after administration of single dose. Controlled drug delivery system Drug delivery System in which maintain constant level of drug in blood and tissue for extended period of time. 3

4. Comparison of drug release profile 4

5. Advantages SR and CRDDS Improve absorption, utilization and there by enhancing bioavailability. Decreased local and systemic side effects reduced gastrointestinal irritation. Reduction in dosing frequency. Better patient acceptance and compliance. Reduced fluctuations in circulating drug levels. Reduction in the health care cost . Bioavailability of certain drugs can be increased. 5

6. Disadvantages of SR and CRDDS Dose dumping. Dose adjustment is difficult. Patient education is required for successful therapy. Patient need to substantial additional information as to the proper used sustained release product. P oor IVIVC. Higher cost of single unit as compared to cost of single conventional unit. Stability problems. 6

7. Drug selection criteria for oral sustained and controlled drug delivery system 1) Physicochemical properties of drug 2) Pharmacokinetic properties of drug 3) Pharmacodynamic properties of drug 7

8. Physicochemical properties of drug Molecular weight of the drug Aqueous solubility of drug Apparent partition or coefficient of drug Drug Pka and ionization at physiological pH Drug stability Mechanism and site of action Biopharmaceutical aspect of route of administration Oral route Intramuscular or subcutaneous route Transdermal route 8

9. 2) Pharmacokinetic properties of drug Absorption rate Elimination half life Rate and extent of metabolism Dosage form index Plasma protein binding 3) Pharmacodynamic properties of drug Therapeutic index or range Plasma concentration response relationship 9

10. Classification of oral sustained and controlled drug delivery system 10

11. 1) Continuous release system These systems release the drug continuously for prolonged period of time along the entire length of GIT with normal transit time . Different systems under this class are- Dissolution controlled release system Diffusion controlled release system Dissolution and diffusion controlled release System Ion exchange drug resin complexes Slow dissolving salts and complexes pH-dependent formulation Osmotic pressure controlled release system Hydrodynamic pressure controlled release system 11

12. 1) Continuous release system Natural polymer Synthetic polymer Semi synthetic polymer 12

13. a) Dissolution controlled release system These system are most commonly employed in the production of enteric dosage forms. Drug present in the system having high aqueous solubility and dissolution rate. Matrix system Matrix system are also called as monoliths since the drug is homogenously dispersed throughout a rate-controlling medium. e.g. Bees wax, carnauba wax, hydrogenated castor oil. 13

14. Reservoir system The drug particle are coated or encapsulated by one of the several microencapsulation Techniques with slowly dissolving materials like Cellulose, PEG, polymethacrylates, waxes, etc. 14

15. b ) Diffusion controlled release system Movement of drug molecules from a region of a higher concentration to one of lower concentration. Matrix system The drug is dispersed in an insoluble matrix of rigid nonswellable hydrophobic materials or swellable hydrophilic substances. Reservoir system These system are hollow containing an inner core of drug surrounded in a water insoluble polymer membrane. 15

16. c) Dissolution and diffusion controlled release system Insoluble membrane Pore created by dissolution of soluble fraction of membrane Entry of dissolution fluid Drug diffusion d) Ion exchange resin-drug complexes Is based on preparation of totally insoluble ionic material Resins are insoluble in acidic and alkaline media they contain ionizable groups which can be exchanged for drug molecules. R-SO 3 – H + + H 2 N – A R-SO 3 - NH 3 + - A R-NH 3 + OH - + HOOC – B RNH 3 + - OOC-B + H 2 O 16

17. e) Slowly dissolving salts and complexes Salt or complexes of drug which are slowly soluble in the GI Fluid can be used for controlled release of the drug. e.g. Penicillin G has been complexed with N,N- dibenzyl ethylene diamine to give benzathine penicillin G. d) Osmotic pressure controlled release system 17

18. e) Hydrodynamic pressure controlled release system Such system are designed to eliminate the influence of GI pH on dissolution and absorption of drugs by formulating then with sufficient amount of buffering agents s.a. salts of phosphoric, citric, or tartaric acids. That adjust the pH to desired value as the dosage form passes along the GIT and permit drug dissolution and release at a constant rate independent of GI pH. f) pH-dependent formulations 18 Drug delivery orifice Shape-retaining housing Collapsible drug reservoir Annular opening Swellable hydrophilic polymer

19. 2) Delayed transit and continuous release system These systems are designed to prolong release of drug with increased residence time in GIT. Such dosage forms are designed to remain in the stomach. Therefore the drug presented in such systems should be stable at gastric pH. This class includes following systems Altered density system Mucoadhesive or Bioadhesive system Size based system 19

20. a) Altered density system If the residence time of drug in the stomach or intestine is prolonged in some way, the frequency of dosing can be further reduced. Altering the density of drug particle, use of mucoadhesive polymers and altering the size of the dosage form. High density pellets Low density pellets b) Mucoadhesive system A mucoadhesive or bioadhesive polymer s.a. Cross-linked polyacrylic acid, when incorpated in a tablet , allow it to adhere to the gastric mucosa or epithelium. c) Size-Based system The diameter of tablet always greater than 2cm which can not Pass through pylorus and can't goes in to intestine. Using high grade polymer like HPMC K200 having high swelling property. 20

21. 3) Delayed release system These systems are fabricated to release the drug only at specific site in the GIT. The drugs those are- Destroyed in stomach or by intestinal enzymes. Known to cause gastric irritation Absorbed from specific site in intestine are formulated in such systems. The two types of delayed release systems are Intestinal release system Colonic release system 21

22. a) Intestinal release system A drug may be enteric coated for intestinal release for Several known reason s.a. to prevent gastric irritation, destabilization in gastric pH. b) Colonic release system Drug are poorly absorbed through colon but may be delivered to such a site for two reason- Local action as in the treatment of ulcerative colitis Systemic absorption of protein and peptide drug like insulin and vasopressin. 22

23. Evaluation of SR and CR Tablets Appearance Friability Hardness Thickness Weight variation Tablet density Drug content In-vitro drug release In-vivo study Diffusion study Stability study 23 Bioadhesion or mucoadhesion test IVIVC Floating capability Kinetic modeling

24. Evaluation of SR and CR Pellets Friability Weight variation Tablet density Drug content Floating capability In-vitro drug release Kinetic modeling In-vivo study Diffusion study Expiry date determination and stability studies Bioadhesion or mucoadhesion test IVIVC 24

25. Evaluation of SR and CR Capsules Weight variation Drug content In-vivo study In-vitro drug release Stability study 25

26. Application of SR and CRDDS Application of SR and CRDDS in following drug delivery system Oral controlled drug delivery system GRDDS Ocular drug delivery system Trasdermal drug delivery system Intestinal drug delivery system Colonic drug delivery system 26

27. Marketed product 27 Tablets Composition Product name Manufacturer Carbamazepine Zen retard Intas Diclofenac sodium Dic -SR Deep pharma limited Diclofenac sodium Nac -SR Systopic Diclofenac sodium Voveran-SR Ciba- Geigy Nifedipine Depine retard Cadila health care Theophylline Theo PA Welcome Capsules Diazepam Elcoin Ranbaxy Diclofenac sodium Diclotal CR Blue cross Indomethacin Indoflam TR Recon Nitroglycerine Angispan Lyka Transdermal Nitroglycerine Nitroderm TTS Ciba-Geigy Nicotine Nicotine patch Ciba-Geigy

28. Conclusion The Sustained release drug delivery system is very helpful in increasing the efficiency of the dose, safety of dose as well as the patient compliance. The controlled release drug delivery system aims to release the drug at the desired rate over extended period of time to maintain the therapeutic level in blood. 28

29. References Brahmankar D.M. and Jaiswal S.B. (2010), Biopharmaceutics and Pharmacokinetics a Treatise. Delhi, Vallabh Prakashan, 2 nd edition, pp.397-463. Dr. Dheeraj T. Baviskar and Dr. Dinesh K. Jain, Novel drug delivery system, Nirali prakashan, 3 rd edition (2016), pp.2.1-2.31. C.V.S Subrahmanyam, Textbook of Biopharmaceutics and Pharmacokinetic, Vallabh prakashan, 2 nd edition(2015), pp.262-284. Ratnaparkhi, M.P. and Gupta Jyoti, P., 2013. Sustained release oral drug delivery system an overview. Terminology,  3 , p.4. Isha, C., Nimrata, S., Rana, A.C. and Surbhi, G., 2012. Oral sustained release drug delivery system:an overview. International research journal of pharmacy,  3 (5), pp.57-62. 29

30. Rao, A.A., Rao, V.N., Devi, A.S., Anil, K., Naik, V.V. and Rajesh, A., 2015. Oral controlled release drug delivery system: an overview. International Journal of Pharma and Chemical Research, 1(1), pp.6-15. Deshpande, A.A., Rhodes, C.T., Shah, N.H. and Malick, A.W., 1996. Controlled-release drug delivery systems for prolonged gastric residence: an overview. Drug Development and Industrial Pharmacy, 22(6), pp.531-539. DIXIT, N. et.al. (2013). Sustained Release Drug Delivery System. Indian Journal of Research in Pharmacy and Biotechnology, 1(3), pp.305-310 . 30 Cont…

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