Desired Release Rate

The desired release profile can be based on various physicochemical mechanisms, supplemented with the mechanical effect of the dosage form itself. The mathematical equations for the release profile in combination with in vitro research can help on directing the development of new preparations. 

The independence from such factors can be tested to a certain extent in vitro, by determination of the dissolution rate under influence of (a simulation of) the variables. The tests described by the Ph. Eur. are limited, namely to the influence of pH [6]. The USP also requires testing for the influence of 15 % ethanol on the dissolution rate (see also Sects. 32.10 and 16.2.3). 

The described physico-chemical mechanisms are applied in various combinations in licensed medicines. The different modified-release dosage forms can be classified in many ways, which can be found in literature. 

Licensed medicines delivering the same active substance with a modified release profile rarely have the same formulation. What can be distinguished is whether the preparation consists of a matrix, a reservoir system, or a combination of both. An example of a combination of a matrix and a membrane is a coated hard gelatine capsule filled with small matrix pellets (mini matrices). When using these complex systems for the preparatimi of other dosage forms, each component should be dealt with differently and independently. 

It can also be distinguished whether the dosage form is monoUthic (mie part) or multi-particulate (consisting of multiple small particles). A monohthic dosage form remains intact or erodes during its residency in the gastro-intestinal tract. A multi-particulate system, on the other hand, disintegrates and spreads. 

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Animal comfort End-user acceptance Desired release rate... 

A formulation for further study could be selected from the region of the top right on the basis of the desired release rate and a reduced pH dependance. 

Microcapsules with desired release rate and patterns can be obtained by carrying out either chemical or physical modifications to the microcapsules. In the case of chemical modifications, the polymeric wall material is modified or, along with active agent, another additive is added. This allows the release of active agent to occur in response to physical/chemical changes in the additive, due in turn to change(s) in the microcapsule environment. Physical modifications involve controlling porosity of the capsule wall, or double encapsulation. The adsorption of an... 

Microcapsules with desired release rates according to the application involved can be prepared by incorporating a selected fluid (solvent), while keeping the other capsule parameters constant. These fluids include dearomatized and isoparaffinic hydrocarbons, aromatic hydrocarbons, acetate derivatives, and blends of these [51], In the preparation of polyurethane-polyurea microcapsules containing hep-tenophos (liquid pesticide, b.p. 64 °C), it has been reported that the porosity of microcapsules can be controlled by the addition of 2-ethoxy ethyl acetate or ethyl acetate in the organic phase containing isocyanate prepolymer and pesticide [52]. 

In this method a reservoir or depot of the pesticide is boimded by a pol5uneric membrane, which protects (and separates) it from the environment and also provides a mechanism for its release. Thus, the specifications for the chemical nature and structure of this membrane are critical in the performance of such formulations. This makes for exacting requirements in the manufacturing processes if the desired release rates are to be consistently obtained in the field. 

Oral controlled drug-release systems are increasingly used for short half-life drugs to reduce peak blood levels and side-eflfects, to maintain optimum drug concentration and to stimulate patient compliance. In order to maintain a constant blood-level of the drug during an extended period, a constant in vitro drug release rate is desired. The most popular controlled-release system is the matrix tablet (Desai et al., 1965). Te Wierik et al. (1996) reported on... 

Maximum Release. The analytical model described above assumes that the liquid phase is completely stagnant. While this may be true in an ideal laboratory experiment where a small sample can be kept isothermal at a specified temperature, in large scale systems where non-isothermal conditions exist, both natural convection and molecular diffusion will contribute to mass transfer. This combined effect, which is often very difficult to assess quantitatively, will result in an increase in fission-product release rate. Therefore, in making reactor safety analyses, it is desirable to be able to estimate the maximum release under all possible conditions. 

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