sustained DDS.ppt
- 2. 2 The period between 1950 to 1970 is considered as period of Sustained drug release The main AIM of preparing sustained release formulation’s was intended to modify and improve the drug performance by Increasing the duration of drug action Decreasing the frequency of dosing Decreasing the required dose employed Providing uniform drug delivery
- 3. 3 The of SRDF’s is to obtain Zero order release from the dosage form. Zero order release is a release which is independent of the amount of drug present in the dosage form. Usually SRDF’s do not follow zero order release but they try to mimic zero order release by releasing the drug in a slow first order fashion. Pharmacological action is seen as long as the drug is in therapeutic range, problems occur when drug concentration is above/below therapeutic range.
- 4. 4 Improved patient compliance: Less frequent dosing Allows whole day coverage. Decreased local and systemic side effects. Decreased GIT irritation. Decreased local inflammation. Better drug utilisation. Decreased total amount of drug used. Minimum drug accumulation on chronic dosing. Improved efficiency in treatment. Uniform blood and plasma concentration. Decreased fluctuation in drug level i.e uniform pharmacological response. Increased bioavailability of some drugs Special effects: SR Aspirin gives symptomatic relief in Arthritis after waking Economy
- 5. 5 DOSE DUMPING :Increase quantity of drug release causes dumping of drug which in turn leads to toxicity. REDUCED POTENTIAL FOR ACCURATE DOSE ADJUSTMENT: Administrating a fraction of drug is not possible. NEED FOR ADDITIONAL PATIENT EDUCATION: “Do not Crush or Chew the dosage unit”. “ Tablet residue may appear in stools”. STABILITY PROBLEMS: The complexity of SRF’s will lead to stability problem. REDUCTION IN SYSTEMIC AVAILABILITY: Example Theophylline, Procainamide and vitamin combinations.
- 6. 6 Retrieval of the drug is difficult in case of toxicity / poisoning / hypersensitive reaction. Higher cost of the formulation. Half life: Drugs having shorter half life (less than one hour) and drugs having longer half life (More than twelve hrs) cannot be formulated as SRDF’s. If a dosage form contains more than 500mgs., of active ingredient formulation of SRDF’s is difficult. If CRDF is required (With New polymers) cost of government approval is very high.
- 14. 31/12/2009 Nepal Pharmaceutical Ltd., Nepal 14 Matrix Type • Also called as Monolith dissolution controlled system. • Controlled dissolution by: 1.Altering porosity of tablet. 2.Decreasing its wettebility. 3.Dissolving at slower rate. • First order drug release. • Drug release determined by dissolution rate of polymer. • Examples: Dimetane extencaps, Dimetapp extentabs. Soluble drug Slowly dissolving matrix
- 15. 31/12/2009 Nepal Pharmaceutical Ltd., Nepal 15 Encapsulation • Called as Coating dissolution controlled system. • Dissolution rate of coat depends upon stability & thickness of coating. • Masks colour,odour,taste,minimising GI irritation. • One of the microencapsulation method is used. • Examples: Ornade spansules, Chlortrimeton Repetabs Soluble drug Slowly dissolving or erodible coat
- 16. 31/12/2009 Nepal Pharmaceutical Ltd., Nepal 16 Matrix Diffusion Types • Rigid Matrix Diffusion Materials used are insoluble plastics such as PVP & fatty acids. • Swellable Matrix Diffusion 1. Also called as Glassy hydrogels.Popular for sustaining the release of highly water soluble drugs. 2. Materials used are hydrophilic gums. Examples : Natural- Guar gum,Tragacanth. Semisynthetic -HPMC,CMC,Xanthum gum. Synthetic -Polyacrilamides. Examples: Glucotrol XL, Procardia XL
- 17. 31/12/2009 Nepal Pharmaceutical Ltd., Nepal 17 Matrix system Rate controlling step: Diffusion of dissolved drug in matrix.
- 18. 31/12/2009 Nepal Pharmaceutical Ltd., Nepal 18 Higuchi Equation Q = DE/T (2A.E Cs)Cs.t)1/2 Where , Q=amt of drug release per unit surface area at time t. D=diffusion coefficient of drug in the release medium. E=porosity of matrix. Cs=solubility of drug in release medium. T=tortuosity of matrix. A=concentration of drug present in matrix per unit volume.
- 19. 31/12/2009 Nepal Pharmaceutical Ltd., Nepal 19 Reservoir System • Also called as Laminated matrix device. • Hollow system containing an inner core surrounded in water insoluble membrane. • Polymer can be applied by coating or micro encapsulation. • Rate controlling mechanism - partitioning into membrane with subsequent release into surrounding fluid by diffusion. • Commonly used polymers - HPC, ethyl cellulose & polyvinyl acetate. • Examples: Nico-400, Nitro-Bid
- 20. 31/12/2009 Nepal Pharmaceutical Ltd., Nepal 20 Reservoir System Rate controlling steps : Polymeric content in coating, thickness of coating, hardness of microcapsule.
- 24. 24 Different methods used are.. BASED ON DRUG MODIFICATION. BASED ON DOSAGE FORM MODIFICATION.
- 25. 25 BASED ON DRUG MODIFICATION: COMPLEX FORMATION DRUG-ADSORBATE PREPARATION . PRO DRUG SYNTHESIS. ION EXCHANGE RESINS.
- 26. 26 Complex formation: The rate of dissolution of solid complex in biological fluids and rate of dissociation of complex in the solution are considered and they depend upon pH and composition of gastric and intestinal fluids. Drug-adsorbate preparation: In this product is insoluble. Drug availability is determined by rate of disabsorption. Pro drug synthesis: They are inactive and need enzymatic hydrolysis for regeneration. Solubility, absorption rate of prodrug must be lower than parent drug.
- 27. 27 Ion exchange resins: They are water insoluble, cross linked polymers containing salt forming groups. The drug is bound to the resin by using chromatographic column or by prolonged contact. Drug release from this complex depends on pH & property of resin. Drug that is attached to the resin is released by exchanging with the ions present in the GIT. Resin+ -Drug- +X- Resin+- X- + Drug- Example: Biphetamine.
- 28. 28 BASED ON DOSAGE FORM MODIFICATION. Microencapsulation: It’s a process in which tiny particles are surrounded by uniform coating (microcapsule) or held in a matrix of polymer (microsphere.) Spray drying is used which involves rapid evaporation of the solvent from the drug surface. Barrier coating: In this one quarter of the granules are in non sustained form for sudden drug release, remaining part are coated for sustained release. Both these granules are filled in hard gelatin capsule or compressed in a tablet, and the release mechanism is by diffusion. Coating material used are fats, waxes.
- 29. 29 Matrix embedding: Drug is dispersed in a matrix of retardant material which may be encapsulated or compressed in a tablet.
- 30. 30 Name Marketer Dosage form Indication Carbotrol Glucotrol Xl Adderall XR Procardia Xl Ortho Evra Dura gesic Shri Us Pfizer Shri US Pfizer Ortho – Mcneil Janssen Oral capsule Oral Tablet Oral Capsule Oral Tablet Trans Dermal Patch Trans Dermal Patch Epilepsy Hyperglycaemia ADHD Angina / Hypertension Contraceptive Chronic pain