Novel Drug Delivery Systems (NDDS) aim to improve drug therapeutic efficacy and safety by ensuring the timely delivery of the drug in the required amounts to the target site.
Controlled release formulations are one such type of NDDS. They release the drug at a predetermined rate to maintain drug concentrations in the therapeutic window for prolonged periods.
The principles guiding controlled release formulations include:
Diffusion Controlled Systems
Dissolution-Controlled Systems
Ion-Exchange Systems
Approaches based on diffusion principle
These are systems in which drug release is controlled predominantly by the process of diffusion through a membrane or a polymer matrix.
I. Reservoir systems:
These have a core of active drug surrounded by a polymer membrane.
The drug diffuses out through this membrane. The rate of drug release is governed by the thickness and nature of the membrane.
II. Matrix systems:
These have drugs dispersed throughout a polymer matrix. As the outer layer gets dissolved and releases the drug, the inner layers become exposed, continuing the release.
For a homogenous matrix:
Approaches based on dissolution principle
Dissolution-Controlled Systems are drug delivery systems in which the rate of drug release is primarily governed by the dissolution of either the drug itself or the polymer in which the drug is encapsulated.
Assuming sink conditions, dissolution process is described by the Noyes-Whitney equation can be applied:
I. Encapsulation Controlled (Reservoir Systems):
In these systems, the drug is encapsulated or surrounded by a polymer shell or coating.
The drug releases as the outer polymer layer dissolves in the surrounding medium.
The rate of drug release is often determined by the thickness and composition of the polymer coating.
Examples: Osmotic pumps, coated pellets.
II. Matrix/Erosion Controlled Systems:
Here, the drug is dispersed uniformly within a polymer matrix.
Two types of release mechanisms:
a. Dissolution controlled: As the matrix dissolves, the drug disperses into the surrounding medium.
b. Erosion controlled: The matrix does not dissolve quickly, but rather erodes over time, releasing the drug.
The rate of drug release is influenced by the type of polymer, drug distribution within the matrix, and the erosion rate.
Examples: Sustained-release tablets, biodegradable implants.
In both systems, maintaining the appropriate drug release rate often requires careful choice and design of the polymer materials used, considering factors like their solubility, degradability, and interaction with the drug.
Approaches based ion exchange principle
Ion Exchange Controlled Systems are drug delivery formulations where the release of the drug is regulated through ionic interactions between the drug and an ion-exchange resin.
Types of Ion Exchange Resins:
1. Cation Exchange Resins:
These resins release positively charged drug ions (cations) in exchange for other cations present in the solution. They typically have acidic functional groups like sulfonic or carboxylic groups.
Example: Sodium Polystyrene Sulfonate (Kayexalate):
Sodium Polystyrene Sulfonate in its sodium form:
[Resin-SO3−Na+]
In the presence of elevated potassium (K⁺) in the gut:
[Resin-SO3−Na+] + K + → [Resin-SO3−K+] + Na+
Here, the resin releases sodium ions (Na⁺) and captures potassium ions (K⁺) from the gut.
2. Anion Exchange Resins:
These release negatively charged drug ions (anions) in exchange for other anions in the solution.
They possess basic functional groups like quaternary ammonium groups.
Example: Cholestyramine (Questran):
Cholestyramine in its chloride form:
[Resin-N(CH3)3+Cl−]
In the presence of bile acids (represented as BA⁻ for simplicity) in the gut:
[Resin-N(CH3)3 + Cl−] + BA− → [Resin-N(CH3)3 + BA−] + Cl−
Here, the resin releases chloride ions (Cl⁻) and captures bile acid anions (BA⁻) from the gut.
Ion Exhange process is described by Langmuir isotherm:
