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Controlled Drug Release Formulations Part II: Novel Systems

5/17/2009

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Controlled Release Drug Delivery System - definition, types, factors impelling transition to rate control delivery systems, classification and design of CRDDS, per oral CRDDS, dental, ocular, and intravaginal / intrauterine controlled release systems have already been dealt with in Part I of the series.

The present series i.e. part II, encompasses Implantable, Injectable CRDDS, Analytical controls and Regulatory considerations of CRDDS and Novel CRDDS

 
1)  IMPLANT CONTROLLED RELEASE DELIVERY SYSTEM :

Lafarge pioneered in 1861, the concept of  implantable therapeutic systems for long-term, continuous drug administration with the development of a subcutaneously implantable drug pellet.  The technique was then rediscovered in 1936 by Deanesly and Parkes, who administered crystalline hormones in the form of solid steroid pellets to mimic the steady, continuous secretion of hormones from an active gland for hormone substitution therapy.

Approaches to development of implantable therapeutic systems:

Historically, the subcutaneous implantation of drug pellet is known to be the first medical approach aiming to achieve prolonged and continuous administration of drugs.  Over the years, a number of approaches have been developed to achieve controlled administration of biologically active agents via. Implantation of insertion in the tissues.  These approaches are outlined as follows:

A.  Controlled drug release by diffusion  

    1.  Membrane permeation-controlled drug delivery using:

            a.  Nonporous membranes

            b.  Micro porous membranes

            c.  Semi permeable membranes

    2.  Matrix diffusion-controlled drug delivery using:

            a.  Lipophilic polymers

            b.  Hydrophilic (swellable) polymers

            c.  Porous polymers

    3.  Micro reservoir dissolution-controlled drug delivery using:

            a.  Hydrophilic reservoir / Lipophilic matrix

            b.  Lipophilic reservoir / Hydrophilic matrix


B.  Controlled drug release by activation 
​ 
  1. Osmotic pressure-activated drug delivery
  2. Vapor pressure-activated drug delivery
  3. Magnetism-activated drug delivery
  4. Ultrasound-activated drug delivery
  5. Hydrolysis-activated drug delivery

 
An ideal implantable therapeutic system should be with minimal tissue-implant interactions, nontoxic, non-carcinogenic, removable if required and should release the drug at a constant, programmed rate for a predetermined duration of medication.  The polymers used in the therapeutic system must not cause irritation at the implantation site, or promote infection or sterile abscess.  The most common polymers used are hydrogels, silicones and biodegradable materials.

In the next post, we shall take up different types of rate controlling methods for implant delivery systems.
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