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Renin Angiotensin Mechanism.

Implantable Drug Delivery Systems.

 

Introduction.

  • Using lower drug concentrations, implantable drug delivery systems may still produce a therapeutic effect because they enable targeted and localized drug delivery. 

  • As a result, they may reduce therapy's potential side effects while providing a chance for higher patient compliance

  • Because it avoids first pass metabolism and chemical degradation in the stomach and intestine, increasing bioavailability, this type of system also has the potential to deliver medications that are typically inappropriate for oral administration.

Ideal Properties:

  1. Environmentally stable

    1. Under the influence of light, air, moisture, heat, etc., implantable systems shouldn't malfunction.

  2. Biostable

    1. Implantable systems shouldn't degrade physicochemically when exposed to biofluids (or medications).

  3. Biocompatible

    1. Systems for implants shouldn't provoke an immune reaction because that could result in the implant being rejected.

  4. Removal

    1. Implantable systems should be removable when required.

  5. Non-toxic or non-carcinogenic

    1. The byproducts of degradation or leached additives ought to be entirely secure.

  6. Systems for implantation should have minimal surface area, a smooth texture, and structural integrity

  7. To prevent irritation, it should have properties that are similar to the tissue in which it will be implanted.

  8. Drugs should be released from implantable systems over a predetermined period of time at a constant rate.

Advantages and disadvantages:

Advantages:

  1. longer and more sustained action.

  2. enhanced control over drug release.

  3. The dose needs to be incredibly low.

Disadvantages:

  1. invasive treatment

  2. Probabilities of device failure

  3. only applies to potent drugs.

  4. issues with biocompatibility.

The concept of implants:

  • Implants for drug delivery are of several types:

  1. In situ forming implants (In situ depot forming systems):

  • In situ precipitating implants:

  • The drugs that make up these implants are dissolved in a biocompatible solvent. 

  • Following subcutaneous (s.c.) or intramuscular (i.m.) injection and contact with aqueous body fluids, the polymer solution precipitates polymers to form implants

  • The following issues with the use of biodegradable microparticles are addressed by in situ precipitating implants:

    • Reconstitution is necessary before injection.

    • being unable to remove the dose that was injected.

    • comparatively difficult manufacturing processes to create a sterile, reliable product.


  • In situ microparticle implants:

  • These implants were developed to address the drawbacks of in situ precipitating implants

  • These are: 

    • high injection pressure

    • local discomfort where the injection was given.

    • fluctuation in the rates of solidification.

    • Depending on the cavity that the implants are introduced (implanted) into, the implants take on an irregular shape.

    • Unwanted high initial burst drug release.

    • possible toxicity of the solvent.

  • Internal phase (drug-containing polymer solution or suspension) and continuous phase (aqueous solution with a surfactant, oil phase with viscosity enhancer and emulsifier) make up these in situ implantable systems.

  • Before administration, the two phases are separately stored in dual-chambered syringes and combined using a connector.

  1. Solid implants:

  • Solid implants are typically cylindrical, monolithic devices that are either injected into the s.c. or i.m. tissues with a large bore needle or implanted through a small surgical incision

  • Because it is simple to implant into subcutaneous (s.c.) tissue, it has poor infusion, slower drug absorption, and little reactivity to foreign substances.

  • These implants contain drugs that may be dissolved, dispersed, or embedded in a matrix of polymers, waxes, or lipids that regulates the release through diffusion, bioerosion, biodegradation, or an activation process, like hydrolysis or osmosis

  • These systems are typically made into spherical pellets, compressed tablets, implantable flexible/rigid molded or extruded rods

  • Silicone, polymethacrylates, elastomers, polycaprolactones, polylactide-co-glycolide, and other materials are used as polymers, while glyceryl monostearate is a wax

  • Typically, drugs like naltrexone, contraceptives, and other such implantable systems are presented

  1. Infusion devices:

  • Infusion devices are intrinsically powered to deliver drugs at a zero order rate, and the drug reservoir can be replenished on a regular basis

  • There are three types of implantable pumps based on the mechanism by which they are powered to release drugs:

    • Drug delivery systems that are activated by osmotic pressure

    • Drug delivery systems that use vapor pressure

    • Drug delivery systems that run on batteries

  1. Osmotic pumps:

  • Osmotic pumps are primarily composed of a semi-permeable membrane that encircles a drug reservoir. 

  • The membrane should have an orifice that allows drug release. 

  • Osmotic gradients will allow for a consistent inflow of fluid within the implant. 

  • This process causes an increase in pressure within the implant, forcing drug release through the orifice. 

  • The constant drug release (zero order kinetics) is enabled by this design.

  • This type of device has a high release rate but has a limited drug loading capacity.

  • Seminal contributions to the history of osmotic systems include the Rose-Nelson pump, the Higuchi-Leeper pumps, the Alzet and Osmet systems, the elementary osmotic pump, and the push-pull or GITSR system

  • Recent developments include the controlled porosity osmotic pump, asymmetric membrane systems, and other approaches.

Osmotic agents:

  • Osmotic agents used in the fabrication of the osmotic device maintain a concentration gradient across the membrane by generating a driving force for water uptake and help to keep drug uniformity in the hydrated formulation

  • Osmotic agents are typically inorganic salts such as sodium chloride, potassium chloride, magnesium sulfate, sodium sulfate, potassium sulfate, and sodium bicarbonate

  • Additionally, sugars such as glucose, sorbitol, sucrose, and inorganic salts of carbohydrates can act as effective osmotic agents. 

Commonly Asked Questions.

  1. Discuss implantable drug delivery systems.

  2. Write a short note on,

    1. Osmotic pumps.

    2. In situ forming implants

    3. In situ microparticle implants.

  3. Give ideal properties, advantages and disadvantages of Implantable Drug Delivery Systems.

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