Polymer- Mechanism of Drug Release brief explaination

 Polymers- Mechanism of Drug release 

Polymer is a macromolecule having different properties. The drug release mechanism of polymer are disscused on below.

1. Dissolution

When drug release by dissolving of polymer by  penetration of dissolution fluid. In Sustained or controlled drug delivery system, drug is dispersed (matrix system) or encapsulated ( individual drug particles) with slowly dissolving polymers. The rate of penetration of the dissolution fluid into matrix determines the drug dissolution and subsequent release. The penetration of dissolution fluid is however, dictated by the matrix, porosity, presence of hydrophobic additives and the wettability of system and surface of particle. In encapsulated system, the coat thickness and its aqueous solubility determine the time required for dissolution of coat one can formulate a repeat action or sustained release product by using a narrow or a wide spectrum of coated particles of varying thickness, respectively (Figure 1). ^[1]

Figure 1: Drug release by dissolution controlled mechanism of polymer

2. Diffusion

Diffusion occurs when the drug passes from the polymer matrix into the external environment. In controlled drug delivery system, drug is homogenously dispersed in a polymer matrix (monolithic matrix system) or drug (solid, dilute solution or highly concentrated solution) within a polymer matrix and surrounded by thin film ( reservoir system). Diffusion occurs when the drug passes from the polymer matrix into the external environment.  With the passage of time and continous drug release, the delivery rate normally decreases in these type of system since the bioactive agent has to traverse a long distance progressively and thereby requires a longer diffusion time for ultimate delivery of drug(s). In swelling controlled drug delivery system, drug release by swelling of polymer followed by diffusion of drug with or without dissolution (Figure 2). ^[1]

Figure 2: Drug release by diffusion controlled mechanism of polymer

3. Dissolution and Diffusion

Drug release by dissolution of polymer followed by diffusion of drug. In controlled drug delivery system consist of the drug core enclosed in partially soluble membrane. Dissolution of part of outer membrane leads to facilitated diffusion of the contained drug through pores in the coating by dissolution and diffusion controlled release mechanism of polymer. ^[1]

Read More

• Polymer- Definition, introduction and Classification

• Properties of Polymer 

• Application of Polymers in Drug Delivery

4. Erosion ^[2]

A) The active agent is covalently attached to the polymer backbone and is released as its attachment to the backbone cleaves by hydrolysis of bond A. Because it is not desirable to release active agent molecules with polymer fragments still attached, reactivity of bond A should be significantly higher than reactivity of bond B (Figure 3).

Figure 3: Drug release mechanism by erosion

B) The active agent is contained in a core surrounded by a bioerodible rate-controlling membrane. Such a system combines the attributes of a rate-controlling polymer membrane, which provides a constant rate of drug release from a reservoir-type device, with erodibility, which results in bioerosion and makes surgical removal of the drug-depleted device unnecessary. Because constancy of drug release demands that the bioerodible polymer membrane remain essentially unchanged during the delivery regime, significant bioerosion must not occur until after drug delivery has been completed. Thus, polymer capsules will remain in the tissue for varying lengths of time after completion of therapy (Figure 4).

Figure 4: Drug release mechanism by erosion with diffusion

C) The active agent is homogeneously dispersed in a polymer and drug release from this monolith is controlled by diffusion, by a combination of diffusion and erosion, or by erosion (Figure 5).

Figure 5: Drug release mechanism by erosion

5. Ion exchange ^[1]

Drug release by reversible exchange of ions ( in drug-ion exchange resin complex). Ion exchange resins are used to sustain the effects of drugs based on the concept that negatively or positively charged drug moieties combine with appropriate resins producing insoluble polysalt resonates. Where R-SO3^-H⁺ and R-NH3⁺OH^- represents cationic and anionic resins, respectively, whereas H2N-A and HOOC-B depicts basic and acidic drug respectively. Where administered orally resins come in contact HCl with pH 1.2 following reaction take place.

R-SO3^-H⁺   + H2N-A       → R-SO3^- + H3N⁺ -A

R-N⁺H3^- + HOOC-B        → R-N⁺H3^-OOC-B + H₂O

Subsequently, when the system reaches intestine, where it is exposed to a fluid of slightly alkaline pH, following reactions occur.

R-SO3^-H3N⁺-A   +  HCl   →  R-SO3^-H⁺  + A-N⁺H3Cl^-

R^-N⁺H3^-OOC-B   +  HCl  → R-N+H3-Cl- + B-COOH

R-SO3^-H3N⁺-A   +  NaCl   →  R-SO3^-Na⁺  + A-N⁺H3Cl^-

R-N⁺H3^-OOC-B   +  NaCl  → R-N⁺H3Cl^- + B-COO^-Na⁺

6. Stimuli Response

 Drug release or drug release induced by sensitivity of polymer such as light, temperature, ultrasound, magnetic, mechanical, electrical, solvent, ionic strength, electrochemical, pH, enzyme and inflammation.

You want to know more about Stimuli responsive polymers , to read in classification of Polymer,  Click here.

References

1.  S.P. Vyas, Roop K. Khar, Controlled Drug Delivery - Concepts and Advances, 1^st ed: 2002, Vallabah Prakashan, Pg.No: 1-50, 294 – 229, 411-446.

2.  Joseph R. Robinson, Vincent H. L. Lee, Controlled Drug Delivery Fundamentals and Applications, 2 nd ed, Marcel dekker, inc, Pg.No : 192-209.