Mechanism of Drug Release

The mechanism of drug release is dependent on the nature of the matrix and on the mode of drug delivery. For example, diffusion of drug through skin is the mechanism 

The drug release kinetics from the different matrices is determined by this empirical equation (commonly referred as power-law expression) [76]  

The value of exponential component n indicates the mechanism of drug transport from the tablet, where and represent the amount of solvent diffused into the matrix at time t and at infinite time (equilibrium state), respectively, is a constant representing the apparent release rate (%/min) that takes into account the structural and geometric characteristics of the release device, and is the diffusion exponent. The value of n is useful for the determination of drug release mechanism. This equation must hold only for the first 60% of the fractional drug release from the tablets 0.6 logiMJMj -0.22), for which the one-dimensional diffusion under a perfect sink condition holds true [76.77]. 

In the case of non-swelling tablets, drug release is generally expressed by Fickian diffusion, for which n = 0.5. For most erodible matrices, the drug release follows zero order kinetics, for which n = 1. In the case of swelling tablets, the drug release is due to a combination of swelling and erosion. They follow non-Fickian release behavior. For them, the value of n lies between 0.5 and 1.0 [78]. The value of n was calculated from the slopes of the log(M/M ) vs log t plot in acidic and neutral pH. 

To describe the drug release kinetics from inter-polymeric networking systems, various types of empirical equations have been developed such as zero-order rate equation, which describes the inter-polymeric systems where the release rate of drug is independent of concentration of the dissolved species. The first-order equation states that the 

---

Figure 15 Mechanisms of drug release from thermosensitive monolithic devices.

Fig. 6. Mechanism of drug release from (a) homogenous, surface-eroding system, and...

Fig. 5. On-off switching mechanism of drug release (Reproduced from J. Biomater. Sci. Polymer. Edn. [Ref. 49] through the courtesy of VSP BV)...

Establishing in vitro in vivo correlation (IVIVC) for modified release dosage form provides a justification for waiving in vivo bioequivalence evaluation only for certain specified post approval changes. Since a correlation is dependent on the mechanism of drug release, it is not used in situations that could potentially alter its mechanism (16). 

Polymer-based systems. Pulsatile release of medicaments can be obtained from polymer-based delivery systems. Based on the mechanism of drug release from the polymer, these systems can be divided into various classes and subclasses. Broadly, they can be classified into three classes delivery by hydrolysis of polymers, delivery by osmotic pressure, and delivery by both hydrolytic degradation and osmotic effects. 

Several types of CDD systems have been designed based on various mechanisms of drug release (Table I). These mechanisms are dependent on the required site of drug delivery, the physicochemical properties of the drug and also of the delivery vehicle (13), Modes of administration can be oral, sublingual, transdermal, rectal, intrauterine, ocular, or parenteral (intramuscular, peritoneal, and subcutaneous routes of injection). 

Properties affecting the mechanism of drug release from hydrogel systems are 1) the equilibrium water content E.W.C. which is determined by the hydrogel composition and detailed structure ... 

Although there may be other contributing mechanisms of drug release, the scanning electron microscopy study does indicate that the highly porous structure may have a major influence on drug release from microspheres prepared in this study. 

Equation (6.94) illustrates that zero-order release kinetics are obtained if drug dissolution controls the release kinetics. However, as soon as the last particle in the matrix dissolves, the controlling mechanism of drug release shifts to Fickian diffusion. Figure 6.19 shows the dissolution-controlled release of KC1 at the early stage of release and the diffusion-controlled release at the later stage of release from an ethyl cellulose tablet. 

Sustained delivery of ophthalmic medications is a novel approach in treating chronic intraocular infections in conditions where systemic administration is accompanied by undesirable side-effects and repeated intravitreal injections carry the risk of infection. The administration of medications by implants or depot devices is a very rapidly developing technology in ocular therapeutics. The various types of implant and mechanisms of drug release have been discussed in general in Chapter 4. 

Pham, A. and Lee, P., Probing the mechanisms of drug release from hy-droxypropylmethyl cellulose matrices, Pharmaceutical Research, Vol. 11, No. 10, 1994, pp. 1379-1384. 

The mechanisms of drug release from dextran matrix occur in the early stage by polymer swelling, and the tablet thickness increases. Soon thereafter, polymer (and drug) dissolution starts occurring. The polymer dissolves because of chain disentanglement. Thus, there is a slow diminution of the thickness because of erosion until, finally, the tablet disappears (time > 480min). 

Mechanisms of drug release from liposomes are not thoroughly understood. It is postulated that upon cellular uptake, the liposome structure is disturbed... 

Huang, H.-P. Mehta, S.C. Radebaugh, G.W. Fawzi, M.B. Mechanism of drug release from an acrylic polymer-wax matrix tablet. J. Pharm. Sci. 1994, 83, 795-797. 

Jensen JL, Appel LE, Clair JH, Zentner GM. Variables that affect the mechanism of drug release from osmotic pumps coated with acrylate/methacrylate copolymer latexes. / Pharm Sci 1995 84 530-533. 

Stella VJ, Rao VM, Zannou EA, Zia V. Mechanisms of drug release from cyclodextrin complexes. Adv Drug Delivery Rev 1999 36(1) 3-16. 

Sutananta W, Craig DQM, Newton JM. An evaluation of the mechanism of drug release from glyceride bases. J Pharm Pharmacol 1995 47 182-187. 

Ruiz N, Ghaly ES. Mechanisms of drug release from matrices prepared with aqueous dispersion of ethylcellulose. Drug Dev Ind Pharm 1997 23(l) I13-7. 

There are several approaches to identifying the mechanism of drug release from pellets. For example, O Connor and Schwartz (130) applied the approach of Higuchi (131) to show that for a series of pellet formulations, they behaved as an inert matrix with a linear... 

Mechanisms of drug release from multiple emulsion systems include diffusion of the dmg molecules from the internal droplets (1), from the medium of the external droplets (2), or by mass transfer due to the coalescence of the internal droplets (3), as shown in Fig. 7.16(b)... 

---