Controlled Drug Delivery System_ppt.pptx

Controlled Drug Delivery System for Pharmaceuticals

1. Associate Professor, Pharmacy, NNRG CO N T R O LL ED D R U G DE L I VE R Y S Y S TEM S G E N E R AL I N T R O DUCT I O N Dr . Beri Sree Giri Prasad

2. D r ug D e li v e ry D r ug d e li v e r y i s t he m e t h o d o f a d m i n i s t e r i ng pharmaceutical compound to achieve a therapeutic e ff e c t i n hu m a ns o r a n i m a l s . . D r ug d e li v e r y c a n b e d o ne t h r o ug h v a r i o us r o ut e s - the oral (through the mouth), topical (skin), trans m u c o s a l ( na s a l , b u c c a l , s ub li ng ua l , v a g i na l , ocular, rectal), parenteral(injection into systemic c i r c u l a t i o n) a nd i nha l a t i o n r o ut e s .

3. The d r ug d e li v e r y s y s t e m c a n f u r t h e r b e d i v i d e d i nt o t w o m a i n t y p e s : 1 . C o n v e nt i o na l d r ug d e li v e r y system . 2 . Novel drug delivery system The c o n v e nt i o na l d o s a g e f o r m s p r o v i d e d r ug r e l e a s e i mm e d i a t e l y a nd i t c a u s e s f l u c t ua t i o n o f d r ug l e v e l i n b l oo d d e p e nd i ng up o n d o s a g e f o r m . . Th e r ef o r e t o m a i nt a i n t he d r ug c o n c e nt r a t i o n w i t h i n therapeutically effective range need novel drug d e li v e r y s y s t e m ( N DD S ) . NDDS is a combination of advanced techniques and newer dosage form with controlled/sustained drug r e l e a s e t o t a r g e t t he a t s p e c i f i c s i t e .

4. C o n t r o ll e d d r ug d e li v e r y vs C o n v e n t i o n a l d r ug d e li v e r y P e r i o d i c a d m i n i s t r a t i o n H i g h c o n c e nt r a t i o n c a n l e a d t o und e s i r a b l e effects L o w c o n c e nt r a t i o ns c a n b e i n e ff e c t i v e Inconvenient N o t a r g e t i ng D r ug c o n c e nt r a t i o n r i s e q u i c k l y t o e ff e c t i v e level. E f f e c t i v e c o n c e nt r a t i o n i s m a i nt a i n e d f o r l o n g e r d u r a t i o n C on v e n t i ona l drug de li v e r y C on t ro l l e d drug de li v e r y

5. Sustained release drug delivery system S ustained release drug delivery system are the ones that achieve slow release of drug over an extended period of time after administration of single dose. In other words, the drug release is simply extended in time i.e. the rate and duration are not designed to achieve a particular profile. Sustained release- steadily over a long period of time

6. C on t r o ll e d R e l e a se Dr u g D e l i v e r y S y s t em Controlled release are drug delivery system which maintain constant level of drug in blood and tissue for extended period of time. It implies A predictability and reproducibility in drug release kinetics In other words, the rate and duration are designed to achieve A desired concentration. Controlled release drug delivery system is a way of designing and formulating a medicine so that the release of drug from it occur in a controlled manner, desirable manner.

7. P h a r m a c e u t i c a l a pp r o a c h es f o r d es i g n i ng S R / CR DD S It is further divided into matrix and reservoir type dissolution controlled release system

8. Control – Dissolution of the drug from the polymer matrix or encapsulated forms. The dissolution process at a steady state is described by Noyes Whitney equation: dc / dt = k A/V (Cs – C ) d c / d t = ( D / h ) A (Cs – C) where, dC/dt = dissolution rate V = volume of the solution k = dissolution rate constant D = diffusion coefficient of drug through pores h = thickness of the diffusion layer A = s u r f ac e a r e a o f t h e e x po se d s o lid Cs = saturated solubility of the drug C = conc. of drug in the bulk solution 42 D is s o l u ti o n c o n t r o lle d r e lea s e s y s te m

9. M A T R IX t y p e F i rst o r d e r d r u g r e l e a s e . T h e re a re 2 m e t h o d s: C o n g e a li n g & A q u e o u s d i s p e rs i o n m e t h o d The drug release is determined by dissolution rate of the polymer. E x a m p l e s: 1 . D i m e t a n e e x t e n c a p s 2 . D i m e t a p p e x t e n t a b s . E N C A P S U L A T I O N t ype ( R e s e r v o i r T ype ) The drug particle are coated or encapsulated by microencapsulation technique The pellets are filled in hard gelatin capsule, popularly called as ‘spansules’. Once the coating material dissolves the entire drug inside the microcapsule is immediately available for dissolution and absorption. Here the drug release is determined by dissolution rate and thickness of polymer membrane wh i c h m a y r a n g e f r o m 1 t o 20 μ it is also Called as Coating dissolution controlled system. Dissolution rate of coat depends upon stability & thickness of coating. O n e o f t h e m i c r o e n c a p su l a t i o n m e t h o d i s u s e d . Examples: 1. Ornade spansules 2. Chlortrimeton Repetabs

10. B ) D i f f u s i o n c on t r o ll ed r e l ea se s y s t em

11. INTRODUCTION This system is hollow containing an inner core of drug. The water insoluble polymeric material surrounds drug reservoir. The drug partitions into the membrane and exchanges with the surrounding fluid by diffusion. The release drug from a reservoir device follows Fick’s first law of diffusion. J = - D dc/dx Where, J = flux, amount/area-time D = diffusion coefficient of drug in the polymer, area/time dc/dx = change in conc. with respect to polymer distance

12. MATRIX Devices A matrix or monolithic device consists of an inert polymeric matrix in which a drug is uniformly distributed. Drugs can be dissolved in the matrix or the drugs can be present as a dispersion. NOTE : Matrix may be HOMOGENEOUS or POROUS with water filled pores. State of presentation of this form affects the various release patterns: Dissolved drug (Fick’s Second law) Dispersed drug (Fick’s First law) Porous matrix (Higuchi’s theory for porous form) Hydrophilic matrix (gelation & diffusion) 64

13. MATRIX Devices Rigid Matrix Diffusion □ Materials used are insoluble plastics such as PVP & fatty acids. Swellable Matrix Diffusion Also called as Glassy hydrogels.Popular for sustaining the release of highly water soluble drugs. Materials used are hydrophilic gums. Examples : Natural- Guar gum, Tragacanth. Semisynthetic -HPMC, CMC, Xanthum gum. Synthetic -Polyacrilamides. Examples: Glucotrol XL, Procardia XL RESERVOIR Devices The drug core is encased by a water-insoluble polymeric materials. The mesh (i.e., the space between macromolecular chains) of these polymers, through which drug penetrates or diffuses after partitioning, is of MOLECULAR LEVEL. The rate of drug release is dependent on the rate of drug diffusion but not on the rate of dissolution. In short, mass transport phenomena at molecular level occurs. Examples: Nico-400 , Nitro-Bid

14. M e t h o d s o f P r e p . ( R E S E R V O I R D e v i c e s) M o s t l y i t i n v o l v e s : C o a t e d B e a d s / P e ll e t s Microencapsulation Coated Beads/Pellets (RESERVOIR Devices) BEADS/PELLETS Coating of drug solution onto preformed cores. Covering of core by an insoluble (but permeable coat). N O T E : P a n c o a t i n g o r a i r - su s p e n s i o n t e c hn i q u e i s g e n e r a ll y u s e d f o r coating. N O T E : P o re f o r m i n g a dd i t i v e s m a y b e a dd e d t o t h e c o a t i n g s o l u t i o n M i c r o e n c a p su l a t i o n ( R E S E R V O I R D e v i c e s) This technique used to encapsulate small particles of drug, solution of drug, or even gases in a coat (usually a polymer coat). Generally, any method that can induce a polymer barrier to deposit on the surface of a liquid droplet or a solid surface can be used to form microcapsules.

15. D e s i g n c o n s i d e r a t i o ns o f c o n t r o ll e d release R o ut e o f d r ug d e li v e r y T a r g e t s i t e P a t i e nt c o nd i t i o n Polymer consideration- Glass transition temperature, D i ff u s i o n c ha r a c t e r i s t i c s , c o m p a t i b il i t y , e a s e o f f o r m u l a t i o n, f a b r i c a t i o n D r ug c o n s i d e r a t i o n s - P h y s i c o c h e m i c a l p r o p e r t i e s , stability, solubility, partitioning, charge protein binding

16. I o n s E x c h a n ge Ba s e d S R / C R F o r m u l a ti o ns : I on - e x c h a n g e s y s tem s g en e r a ll y u s e r e s i n s c om p o s ed of w a ter insoluble cross-linked polymers. These polymers contain salt-forming functional groups in repeating positions on the polymer chain. The drug is bound to the resin and released by exchanging with appropriately charged ions in contact with the ion-exchange groups Dissolution & Diffusion Controlled Release System: Drug is encapsulated in partially soluble membrane, pores are created due to soluble parts of coating film which permits entry of aqueous medium into core and drug dissolution starts by diffusion of dissolved drug out of system. Mixture of water s ol u b l e P V P a n d w a t er in s olu b le e t h yl c ell u l o s e is u s ed f or th is purpose.

17. W a ter p e n e t r a ti o n / Os m otic P r es s u r e C o nt r olled N DD S : D r u g m a y b e o s m o t i c a l ly a c t i v e or d r u g m a y b e c om b in ed w ith o s m oti c a ll y a c ti v e s a l t s l i k e N a C l . Osmotic Pressure Based SR/CR Formulations: In this system, the flow of liquid into the release unit driven by a difference in osmotic pressure between the inside and the outside of the release unit is used as the release-controlling process.