Formulation principle

Anyone working in a laboratory wOl have access to information that is not public. If the employer is engaged in development work, for instance, news of such work should be confidential. A new employee may be required to sign a secrecy agreement under which all developments made by the employee become the company s exclusive property. When signing such an agreement, the author made certain that some formulation principles which he had developed prior to employment with that company were excluded. 

Disregarding such chemical-specific properties as dissociation constants (in the case of ionic compounds), particle size, and polymorphism, as well as side effects of viscosity, binding to vehicle components, complex formulation, and the like, the following formulation principles arise ... 

Different formulation principles, dosage forms, and DDSs are commonly evaluated in animal models, and attempts are made to predict human absorption on the basis of such studies.80 Human studies are also conducted in some cases to confirm predictions from animal models. Chiou et a 1.81,82 demonstrated that there is a highly significant correlation of absorption (r2 = 0.97) between humans and rats with a slope near unity. In comparison, the correlation of absorption between dog and human was poor (r2 = 0.512) as compared to that between rat and human (r2 = 0.97). Therefore, although dog has been commonly employed as an animal model for studying oral absorption in drug discovery and development, one may need to exercise caution in the interpretation of data obtained. 

The assessment of the quality of a result must be drawn from a number of observations of the laboratory, the personnel, the methods used, the nature of the result, and so on. The great leap forward in understanding quality came in the twentieth century when people such as Deming, Shewhart, Ishikawa, and Taguchi formulated principles based on the premise that the quality of a product cannot be controlled until something is measured (Deming 1982 Ishikawa 1985 Roy 2001 Shewhart 1931). Once measurement data are available, statistics can be applied and decisions made concerning the future. 

Below we will discuss each of these formulation principles in terms of basic release mechanisms and the advantages or drawbacks associated with the different formulations and manufacturing processes. However, drug release from all kinds of ER formulations starts with hydration of the formulation and water diffusion into the system. The presence of water in the formulation facilitates the start of the dissolution process of the drug, whereby the dissolved drug can be released from the formulations. 

The main principles for oral extended drug release reviewed here are the membrane-coated reservoir systems and hydrophilic or hydrophobic matrix systems. They all have advantages and drawbacks and Table 3 summarizes some aspects of the different formulation principles. 

A typical spouted bed has a substantial depth, which in the case of a cylindrical vessel is usually at least of the order of two column diameters, measured from the inlet orifice to the surface of the annulus. If the bed is much shallower, the system becomes hydrodynamically different from true spouting. The situation in this respect is similar to that for gas-fluidized beds, where the generally formulated principles of fluidization are not applicable to very shallow beds. 

This section will discuss the formulation principles of Softgels, including gelatin shell and fill formulations. 

Furthermore, pharmacokinetic administration, distribution, metabolism and excretion (ADME) factors affect drug bioavailability, efficacy and safety, and, thus, are a vital consideration in the selection process of oral drug candidates in development pipelines. Since solubility, permeability, and the fraction of dose absorbed are fundamental BCS parameters that affect ADME, these BCS parameters should prove useful in drug discovery and development. In particular, the classification can used to make the development process more efficient.For example, in the case of a drug placed in BCS Class II where dissolution is the rate-limiting step to absorption, formulation principles such as polymorph selection, salt selection, complex formation, and particle size reduction (i.e., nanoparticles) could be applied earlier in development to improve bioavailability. 

For illustration of basic formulation principles, matrices of cellulose ethers, HPMC in particular, are discussed here. Nevertheless, the fundamentals for the design and performance of the most hydrophific matrices remain the same. 

Since the administration routes are mainly parenteral, the formulation has to be injectable. An injectable formulation requires specific excipients, ways of preparation and formulation types liquid, suspension, or solid formulations. In the development of protein drugs, various formulation principles are used. In Table 5, examples of some of the formulation principles are given. 

SUBSTANCE CREATIVE PHASE F. Which formulation principles... 

Formulation principles chosen for Class 1 compounds are normally straightforward. Aqueous solutions and in situ suspensions cover the needs for an early formulation. 

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