Dosage form application

When requesting a BCS-based waiver for in vivo BA/BE studies for IR solid oral dosage forms, applicants should note that the following factors can affect their request or the documentation of their request ... 

Fortunately, automated fiber-optic probe-based dissolution systems have begun to appear for these solid dosage-form applications. One such system uses dip-type UV transflectance fiber-optic probes, each coupled to a miniature photodiode array (PDA) spectrophotometer to measure drug release in real time. This fiber-optic dissolution system can analyze immediate- and controlled-release formulations. The system is more accurate and precise than conventional dissolution test systems, and it is easier to set up than conventional manual sampling or automated sipper-sampling systems with analysis by spectrophotometry or HPLC. 

S. Turco and R. E. King, Sterile Dosage Forms, Their Preparation and Clinical Application, Lea and Eebiager, Philadelphia, Pa., 1974. 

Scope of Inspection Short description of the inspection (Product related, process related inspection and/or General GMP inspection, reference to specific dosage forms where appropriate). The reason for the inspection should be specified (e.g. new marketing application, routine, investigation of product defect. 

For many drug delivery applications, the preferred method of delivery of the dosage form is by injection. For controlled release applications, the most frequently used approach to allow this method of administration is to prepare microspheres of the polymer containing the drug to be delivered. Several different techniques have been developed for the preparation of microspheres from polyanhydrides. 

Bourquin J, Schmidli H, van Hoogevest P, Leuenberger H. Application of artificial neural networks (ANN) in the development of solid dosage forms. Pharm Dev Technol 1997 2 111-21. 

This chapter describes the basic principles involved in the development of disperse systems. Emphasis is laid on systems that are of particular pharmaceutical interest, namely, suspensions, emulsions, and colloids. Theoretical concepts, preparation techniques, and methods used to characterize and stabilize disperse systems are presented. The term particle is used in its broadest sense, including gases, liquids, solids, molecules, and aggregates. The reader may find it useful to read this chapter in conjuction with Chapters 8, 12, and 14, since they include some of the most important applications of disperse systems as pharmaceutical dosage forms [1]. 

KOR Lehmann. Chemistry and application properties of polymethacrylate coating systems. In JW McGinity, ed. Aqueous Polymeric Coatings for Pharmaceutical Dosage forms, 2nd ed. New York Marcel Dekker, 1997, pp 101-176. 

Historically, the oral route of administration has been used the most for both conventional and novel drug-delivery systems. There are many obvious reasons for this, not the least of which would include acceptance by the patient and ease of administration. The types of sustained- and controlled-release systems employed for oral administration include virtually every currently known theoretical mechanism for such application. This is because there is more flexibility in dosage design, since constraints, such as sterility and potential damage at the site of administration, axe minimized. Because of this, it is convenient to discuss the different types of dosage forms by using those developed for oral administration as initial examples. 

Applicability All plastics Dry oral dosage forms Liquid oral... 

As the list of applications illustrates, the techniques of optimization are not limited to tablets or even to solids. Any dosage form and any process should be amenable to this type of experimentation and analysis. From the most simple formulation to the most complicated one, there are ingredient levels and processing steps that can be varied, and any information on the result of such variation should be useful to the formulator. 

Where an unusual excipient is chosen, or where an established excipient is chosen for a dosage form that results in its administration by a novel route of administration, then additional data will need to form part of the application. In effect, a novel excipient will need to be supported by data similar to those required for a new drug, with full supporting data including composition, function, and safety. Novel excipients include the components of the matrix in prolonged release products, new propellants, and new permeability enhancers. The exception to this need for extensive supporting data would be for a material already approved for food use and administered by the oral route or a material already approved for cosmetic use with a topical route of administration. In all cases the quality of the excipients has to be described adequately and shown to be satisfactory (which will depend on its role). 

This section of an application includes the full details of the composition of the product including any materials that do not appear in the final dosage form— e.g., solvents. Consideration also has to be given to the therapeutic activity of the product, the posology (dosing), and the route of administration. 

Manufacturing validation data, which should aim to identify the critical process steps, especially for nonstandard manufacturing processes such as for new dosage forms, should be discussed in the development pharmaceutics section of the application. Validation data may be accepted based on closely related products. In-process control tests and acceptance limits should be included for any aspect where conformity with the finished product tests cannot otherwise be guaranteed (e.g., mixing, granulation, emulsification and nonpharmacopeial sterilization processes). 

There are several unique topical dosage forms for animals. Four types of which the pharmacist should have a basic understanding or awareness are (a) pour-on/spot-on applications, (b) dust bags, (c) dips, and (d) flea and tick collars. These are used for treatment and prevention of internal and external parasites. 

Membrane diffusion illustrates the uses of Fick s first and second laws. We discussed steady diffusion across a film, a membrane with and without aqueous diffusion layers, and the skin. We also discussed the unsteady diffusion across a membrane with and without reaction. The solutions to these diffusion problems should be useful in practical situations encountered in pharmaceutical sciences, such as the development of membrane-based controlled-release dosage forms, selection of packaging materials, and experimental evaluation of absorption potential of new compounds. Diffusion in a cylinder and dissolution of a sphere show the solutions of the differential equations describing diffusion in cylindrical and spherical systems. Convection was discussed in the section on intrinsic dissolution. Thus, this chapter covered fundamental mass transfer equations and their applications in practical situations. 

W Addicks, G Flynn, N Weiner, C Chiang. Drug transport from thin applications of topical dosage forms Development of methodology. Pharm Res 6 377, 1988. 

Although, the pH-partition hypothesis has not been found to be universally applicable, it has resulted in the recognition of the important contribution of GI pH to permeability and to the dissolution rate of solid dosage forms. This theory does not consider the solubility of the drug, which is a critical physicochemical parameter in the oral absorption process. Dressman et al. [34] developed an absorption potential concept that takes the two parameters into account. The absorption potential is defined as... 

Provide either in vitro or in vivo assay results for representative compounds, describe how the in vitro or in vivo assay protocol is performed, and describe how and why the test results demonstrate that the tested compounds exhibit a useful pharmaceutical property. Ideally, provide and link in vitro assay results to in vivo assay results that in turn demonstrate that the claimed compounds can be used to treat or prevent a disease. Describe how to administer the application s compounds and intended administration recipients (e.g., humans), including dosage amounts and dosage forms (e.g., pills, tablets, capsules), possible ways of administering the dosage... 

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