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Zahid enzyme activated and osmotic pressure activated drug delivery
- 1. ZAHID HUSAIN M.Pharm (Pharmaceutics) Faculty OfPharmacy, IU, Lucknow
- 2. CLASSIFICATION OF RATE– CONTROLLED DRUG DELIVERY SYSTEMS (DDS): 1. Rate programmed DDS (1st Generation controlled DDS) 2. Activation modulated DDS (2nd Generation controlled DDS) A. Osmotic pressure activated DDS B. Enzyme – activated DDS 3. Feedback regulated DDS (3rd Generation controlled DDS) 4. Site specific targeting DDS (4th Generation controlled DDS)
- 3.
- 4. Introduction 1. Osmotic drugdelivery uses the osmotic pressure for controlled delivery of drugs by using osmogens. 2. Osmosis : It refers to the process of movement of solvent from lower concentration of solute towards higher concentration of solute across the semipermeable membrane. 3. Osmotic pressure: The pressure exerted by the flow of water through a semipermeable membrane separating two solutions with different concentrations of solute. 4. These systems can be used for both route of administration i.e. oral and parenterals.
- 5. Principle of osmosis Abbe Nollet first reported osmotic effect in 1748, but Pfeffer in 1877 had been the pioneer of quantitative measurement of osmotic effect. Van’t Hoff established the analogy between the Pfeffer results and the ideal gas laws by the expression, π = n2RT Where, n2 = represents the molar concentration of sugar (or other solute) in the solution, R = depict the gas constant, T = temperature.
- 6. Osmotic Pressure Activated (ClassificationBy : Physical Means) Activation- Modulated DDS
- 7. Osmotic Pressure ActivatedDDS Semi-permeable Membrane. (cellulose esters) Drug reservoir ( API + osmotic agent) Delivery Orifice
- 8. For thedrug delivery system containing a solution formulation, the intrinsic rate of drug release is defined by, Q = Pw Am ( πs – πe ) t hm For the drug delivery system containing a solid formulation, the intrinsic rate of drug release is defined by, Q Pw Am ( πs – πe ) Sd t = hm
- 9. Where, Q/t - rateof drug release Pw - permiability of semipermiable housing Am -effective S.A. of semipermiable housing hm - thickness of semipermiable housing (π s - π e) – Differential osmotic pressure b/w DDS with osmotic pressure ps & environmental osmotic pressure pe Sd – Aqueous solubility of drug contained in the solid formulation.
- 10. Basic component ofosmotic DDS 1. Drug : itself may act as osmogen otherwise osmogenic salt can be added in formulation. 2. Semipermeable membrane: Sufficient wet strength and water permeability Should be biocompatible and rigid Should be sufficient thick to withstand the pressure within the device Any polymer that is permeable to water but impermeable to solute can be used as a coating material in osmotic devices Ex. Cellulose Acetate, Cellulose Triacetate and Ethyl Cellulose. 3. Hydrophilic and hydrophobic polymers :( CMC, HEC, HPMC )
- 11. 4. Wicking agent: ( SLS, PVP, bentonite ) 5. Solubilizing agent :(PVP, CD, PEG ) 6. Osmogens:( NACL, KCL) 7. Surfactants : (poly oxyethylenated caster oil) 8. Coating solvent : ( acetone and methanol 80:20,acetone and water 90:10 ) 9. Plasticizer : ( phthalates, benzoates, TEC ) 10. Flux regulator : ( poly propylene, poly butylene ) 11. Pore forming agent:( Calcium nitrate , potassium sulphate)
- 12. EVALUATION 1. IN-VITRO EVALUATION 2.IN-VIVO EVALUATION
- 13. Marketed Products 1. ProductsIncorporating ALZA's OROS® Technology A. Cardura® XL (doxazosin mesylate) sold in Germany for the treatment of hypertension. B. Covera-HS® (verapamil) a Controlled Release system for the management of hypertension and angina pectoris. C. Sudafed® (pseudoephedrine) for 24-hour relief of cold and other respiratory allergies. D. Procardia XL® (nifedipine) extended-release tablet for the treatment of angina and hypertension. 2. Products Incorporating ALZA's DUROS® Implant Technology A. Viadur® (leuprolide acetate implant) delivers leuprolide continuously for 12 months.
- 14. Osmotic Agent sodiumphosphate sodium chloride
- 15. Advantages 1. Zero orderrelease 2. High release rate 3. High degree of IVIVC 4. Production scale up is easy 5. Increase efficacy of drug 6. Controlled drug delivery 7. Reduce dosing frequency
- 16. Disadvantages 1. Expensive 2. Chanceof toxicity due to dose dumping 3. Release of drug depends on : - size of drug port - surface area - thickness and composition of membrane
- 17. ENZYME - ACTIVATEDDRUG DELIVERY SYSTEM
- 18. Enzyme - ActivatedDrug Delivery System (Classification By : Biochemical Means) Activation- Modulated DDS
- 19. • This typeof biochemical system depends on the enzymatic process to activate the release of drug. • Drug reservoir is either physically entrapped in microspheres or chemically bound to polymer chains from biopolymers (albumins or polypeptides). • The release of drug is activated by enzymatic hydrolysis of biopolymers (albumins or polypeptides) by specific enzyme in target tissue.
- 20. Ex. Albuminmicrospheres release 5-fluorouracil in a controlled manner by protease – activated biodegradation.
- 21.