Dosage form requirements

Design of a controUed release dosage form requires sufficient knowledge of both the desired therapy to specify a target plasma level and the pharmacokinetics. The desired dmg input rate from a zero order system may be calculated by ... 

Two unique sample tests (e.g., different analysts, instruments, reagents, and standard preparations) performed within the same laboratory would establish the method s intermediate precision. If the dosage form requires the use of a sinker, the sinker specified in the method should be used in precision testing. 

Critical process steps are operations performed during dosage-form manufacture that can contribute to variability of the end product if not controlled. Since each type of dosage form requires different machinery and unit operations to produce the end product, the critical process steps will also differ. For each product considered suitable for retrospective validation, a list of these steps must be compiled following careful analysis of the process by technically competent persons. In a similar manner, in-process and finished-product tests should be screened to identify those that may be of some value. As a rule, tests in that the outcome is quantitative will be of greatest interest. 

A rational approach to dosage form design requires a complete understanding of the physicochemical and biopharmaceutical properties of the drug substance. For example, the successful design of an efficacious oral dosage form requires an understanding of the... 

The process equipment should cover a wide range of sizes, rmits, volumes, and operating conditions, e.g., speeds, for maximum flexibility in relationship to batch size and sterile dosage form requirements. Examples of pilot plant equipment utilized for the manufacture of sterile products are shown in Fig. 1. 

There have also been several references to the use of carrageenan in chewable tablets having a confectionary texture.This approach to creating a novel dosage form requires the use of both i-carrageenan and K-carrageenan, to prevent moisture loss and texture changes that occur over time. 

Parenteral dosage forms require extensive testing of sterility and biological impurity contamination because of the high sensitivity of this administration route. These same sterility standards do not apply to solid and... 

Another issue is reproducibility. The formulation may work perfectly in an in vitro test system, but the dosage form requires aerosolization, and lung deposition is a function of the characteristics of the aerosol (dose, mass concentration, droplet/particle size, etc.) and the nature of the inspiratory maneuver, a factor that the patient has control over. These factors can influence performance to a far greater extent than can be built into a particle, and thus the term controlled does not seem a defensible objective for pulmonary delivery. The vagaries of the deposition profile and of the amount that will deposit also imply that sustaining a certain drug concentration is a difficult proposition, but the loosest definition extended release, seems an acceptable goal within the boundaries set by the clearance mechanisms. 

Providing a comprehensive characterization of pharmaceutical dosage forms requires a multi-instrumental approach as no single surface analytical technique can ascertain both the chemical and morphological nature of the surfaces. To this end, SPM, XPS, and ToF-SIMS have been used as complementary techniques with which to characterize the surface nature of dosage forms (141,143-145). 

The development of an API into a viable dosage form requires a vast amount of information to be gathered at the pre-formulation stage. Gathering knowledge of the crystal form diversity exhibited and evaluation of physicochemical profiles of thermodynamically stable forms are activities that facilitate form selection for development of a product. Crystal form diversity of the API is often thought of as its propensity to exhibit polymorphism, but it can also be described further by multi-component phases such as salt forms, solvates, hydrates and co-crystals, all of which may, too, be polymorphic (see Figure 3.1) [3-5]. 

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