Oral controlled drug delivery systems - Various Approaches

these are the drug delivery systems which are given orally and the drug release is such that it releases at a controlled way at a predetermined rate for a particular period of time.

1. ORAL CONTROL DRUG DELIVERY SYSTEMS SIVASWAROOP YARASI

2. Introduction: The primary objective of controlled drug delivery is to ensure safety and improve efficacy of drug as well as patients compliance through better control of plasma drug level and less frequent dosing. “An ideal controlled drug delivery system is the one which delivers thr drug at a predetermined rate, locally or systemically, specific period of time”

3. Oral controlled DDS: The controlled release system for the oral use are mostly solids and based on diffusion, dissolution or a combination of both mechanisms in the control of release rate of drug. The goal is to achieve better therapeutic success compared to conventional dosage form of same drug. This could be achieved by improving pharmacokinetics profile, patient compliance and convenience in therapy.

4. Advantages: Improved patient compliance: improved patient compliance is due to, reduced frequency of administration. Reduced side effects due to low dose. Less fluctuating plasma drug level Better stability of drug. Reduction in drug accumulation with chronic therapy Reduction in drug toxicity (local/systemic). Improvement in bioavailability of some drugs because of spatial control.

5. Classification/approaches:

6. Dissolution controlled release: Easiest to design. Drug with slow dissolution rate is inherently sustained E.g. griseofulvin, digoxin, and salycilamide act as natural prolonged release products. Others aluminium aspirin, ferrous sulphate and benzamphetamine produce slow dissolving from when it comes to contact with GI fluids. Basic principle: If the dissolution process is diffusion layer controlled where the rate of diffusion solid sureface through a unstirred liquid film to bulk solution is rate limiting the flux is ‘j’ is given by

7. J=-D(dc/dx) Where, D= Diffusion coefficient. dc/dx = concentration gradient between the solid surface and bulk of solution.

8. Types of dissolution controlled release products: Encapsulation/ coating dissolution controlled system (reservoir devices)

9. Matrix (or monolith)/ embedded dissolution controlled system. Drug is homogeneously dispersed throughout a rate controlling medium matrix system. Waxes are used beeswax, carnauba wax, hydrogenated castor oil etc.

10. Diffusion controlled release system: Rate controlling step is diffusion of dissolved drug through a polymeric barrier. Broadly classified into Reservoir type Matrix type

11. Reservoir type (or laminated matrix devices): Drug is surrounded by a water insoluble polymer membrane. Coating or microencapsulation are used to apply polymer. Polymers like HPC, EC and polyvinyl acetate are used commonly. Mechanism: drug partitioning into membrane with subsequent release into the surrounding fluid by diffusion.

12. The rate of drug release explained by Ficks law of diffusion. Dm/dt = DSK(AC)/L S= active surface area. D= diffusion coefficient of the drug across the coating membrane. L = diffusional path length (thickness of polymer coat). AC = concentration difference across L. K= partition coefficient of drug between polymer and external medium.

13. Matrix diffusion controlled system: Drug is dispersed in insoluble matrix rigid non swellable hydrophobic materials PVC and fatty materials like stearic acid bees wax etc or swellable hydrophilic substances like (glassy hydrogel) gums (Natural) – guar gum, tragacanth , Semi synthetic – HPMC, CMC xanthan gum. Synthetic – polyacrylamides. Mechanism: initial dehydration of hydrogel – swells – drug diffuses out slowly.

14. Ion exchange resin: Ion exchange resins are cross-linked water-insoluble polymers carrying ionizable functional groups. These resins are used for taste masking and controlled release system. The formulations are developed by embedding the drug molecules in the ion-exchange resin matrix and this core is then coated with a semi permeable coating material such as Ethyl Cellulose.  This system reduced the degradation of drug in GIT. The most widely used and safe ion-exchange resin is  divinylbenzene sulphonate .  In tablet formulations ion-exchange resins have been used as disintegrant .

15. Ion activated drug delivery system: An ionic drug can be delivered by ion activated drug delivery system. In electrolyte medium, such as gastric fluid, ions diffuse into system, react with drug resin complex and triggers the release of ionic drug. Drugs suitable for resinate preparations: Should have acidic or basic groups. Half-life – 2 to 6 hrs. Should be absorbed from all regions of GIT Drug should be sufficiently in the gastric juice.

16. Osmotic controlled drug delivery system: Osmosis is defined as the movement of solvent from lower to higher concentration through semi permeable membrane. Osmotic pressure is the hydrostatic pressure produced by a solution in a space divided by a semi permeable membrane due to difference in concentration of solutes. Principle: Osmotic pressure is the driving force that generates constant drug release. In this system the drug reservoir can be solution or solid formulation and is placed in within the semi permeable membrane housing with controlled water permeability.

17. The drug is activated to release in the solution form at a constant rate through a special delivery orifice. Release of drug is activated by osmotic pressure and controlled at a rate determined by water permeability, effective surface area of semi permeable housing and osmotic pressure gradient. The volume flow of water into core reservoir dv/dt is expressed as: dv/dt = K A/ h ( Δπ-Δ p) K, A & h= Membrane permeability, effective surface, area & thickness of semi permeable membrane, Δπ= osmotic pressure difference, Δ p= hydrostatic pressure difference.

18. Basic components of osmotic pumps:

19. Oral osmotic pumps: Types: Single chamber: Elementary osmotic pump Multiple chamber: Push pull osmotic pump Osmotic pump with non expanding second chamber Specific osmotic pumps: Controlled porosity osmotic pumps. Monolithic osmotic pumps. Osmotic bursting osmotic pumps.

20. pH independent systems: Most drugs are either weak acids or weak bases. The release from controlled release formulation is pH dependent. However buffers such as salts of amino acids, citric acid, phthalic acid phosphoric acid or tartaric acid can be added to formulation to maintain a constant pH thereby rendering pH independent drug release. A buffered formulation is prepared by mixing a basic or acidic drug with appropriate pharmaceutical excipient and coating with GI fluid permeable film forming polymer. When GI fluid permeates through the membrane, the buffering agents adjust the fluid inside to suitable constant pH thereby rendering a constant rate of drug release.

21. Altered density system: These are also called floating systems or hydrodynamically controlled systems. These are low density systems that have sufficient buoyancy to float over the gastric contents and remain buoyant in the stomach without affecting the gastric emptying rate for prolonged period of time. While the system is floating the drug is released slowly at desired rate. Selection of drug candidate: Drug must be absorbed from the upper part of GIT. Drugs that are acting locally in stomach. Drugs that are poorly soluble at alkaline pH. Drugs that degrade in the colon.

22. Types: Effervescent system Non effervescent system

23. High density approach: in this density of pellets must exceed that of normal stomach content and should therefore be at least 1.4g/cm 3  . In preparing such formulations, drugs can be coated on heavy core or mixed with heavy inert materials such as barium sulphate, titanium dioxide, iron powder and zinc oxide. The weighted pellets can be covered with a diffusional controlled membrane.