General chapter dissolution

A recent addition to General Chapter Dissolution <711> allows for the addition of enzyme to the dissolution medium. This is justified when gelatin-coated tablets or gelatin-encapsulated products exhibit a slow-down in the dissolution rate attributed to the crosslinking of the gelatin. The addition of enzyme will break up the crosslinking and therefore remove the... 

During the dissolution test, the hydrodynamic aspects of the fluid flow in the vessel have a major influence on the dissolution rate (1). Therefore, the working condition of the equipment is of critical importance. In this chapter, the qualification and calibration of the equipment referred to in the two USP General Chapters related to dissolution, < 711 > Dissolution and < 724 > Drug Release (2), will be discussed. Sources of error when performing dissolution... 

The USP Dissolution General Chapter < 711 > describes the basket (Apparatus 1) and paddle (Apparatus 2) in detail. There are certain variations in usage of the apparatus that occur in the industry and are allowed with proper validation. The literature contains a recommendation for a new USP general chapter for dissolution testing (6). In this article, guidance for method validation and selection of equipment is described. It may be a useful guide when showing equipment equivalence to compendial equipment. 

A general chapter giving the dissolution test for solid oral dosage forms was first described in the EP in 1991 (20). As mentioned above, the EP has no product monographs in which to elaborate specific dissolution procedures. 

United States Pharmacopoeia, USP 26, National Formulary 21. General Chapter 711 Dissolution United States Phar-macopeial Convention Rockville, MD, 2002 2155—2156. 

European Pharmacopoeia 4th Edition 2002. General Chapter 2.9.3. Dissolution Test for Solid Dosage Forms Directorate for the Quality of Medicines of the Council of Europe Germany 2001 194-197. 

United States Pharmacopeia, General Chapters Physical Tests and Determinations <711 > Dissolution, Official Compendia of Standards, USP 25, NF 20, p. 2011, 2002. 

The United States Pharmacopeial Convention Inc. 2006. General Chapter <711> Dissolution in USP29-NF24 Supplement 2. 

There are several FDA guidances and USP general chapters devoted to dissolution and in vitro release testing. The most relevant FDA guidances are listed below ... 

The USP General Chapters that contain pertinent information regarding dissolution and drug release testing are as follows 5-8... 

USP General Chapter <711> Dissolution,5 describes the basic operation of these apparatuses in detail. The Apparatus section describes the basic parameters or operational qualifications and usually provides tolerances to these operational variables. Operational variables for the basket are the following ... 

The apparatus suitability test described in USP General Chapter <711> Dissolution is equivalent to a performance qualification.5 The determination of suitability of a test assembly to perform dissolution testing must include conformance to the dimensions and tolerances of the apparatus. In addition, the critical test parameters that have to be monitored periodically include volume and temperature of the dissolution medium, rotation speed (Apparatuses 1 and 2), dip rate (Apparatus 3), and flow rate of medium (Apparatus 4). This test requires that the USP Calibrator Tablets (now known as Performance Verification Standard Tablets) be tested the dissolution results must be within the ranges stated in the certificate of the calibrator tablets. The performance verification standard tablets include USP Chlorpheniramine Maleate Extended-Release Tablets RS, USP Prednisone Tablets RS, and USP Salicylic Acid Tablets RS. 

When developing a dissolution method, the process should begin with a familiarity of the literature on method development. There are many good articles,21,22 books,9 11 and the aforementioned new USP Informational General Chapter <1092> The Dissolution Procedure Development and Validation.8 Some of the key considerations in dissolution method development are discussed below. 

USP Informational General Chapter <1092> The dissolution procedure development and validation. USP 30, Volume 1, 2007, 579-584. 

USP General Chapter on Dissolution <7M>, United States Pharmacopeia 30—National Formulary 25, The United States Pharmacopeial Convention, Inc., Rockville, MD, 2007,... 

USP-NF monographs include assays and various analytical methods—identification, dissolution, content uniformity, etc. USP-NF also provides guidance and standards on biotechnology, radiopharmaceuticals, pharmacy compounding, and pharmaceutical waters. General chapters outline requirements for microbiological, biological, chemical, and physical tests and assays. 

Generally, such a remarkable restriction of metal dissolution results not only from the formation of a thin surface oxide film but also from the formation of a comparatively thick film such as silver chloride or zinc chloride. In this chapter, however, we use the term passive film only for compact and thin oxide films. 

In the previous chapter on sample preparation for chromatographic analysis the principal objective has been to secure dissolution of analytes in a suitable solvent and removal from the solution of as many interfering compounds as possible. General sample handling... 

This chapter provides analytical solutions to mass transfer problems in situations commonly encountered in the pharmaceutical sciences. It deals with diffusion, convection, and generalized mass balance equations that are presented in typical coordinate systems to permit a wide range of problems to be formulated and solved. Typical pharmaceutical problems such as membrane diffusion, drug particle dissolution, and intrinsic dissolution evaluation by rotating disks are used as examples to illustrate the uses of mass transfer equations. 

This chapter describes some of the properties of solids that affect transport across phases and membranes, with an emphasis on biological membranes. Four aspects are addressed. They include a comparison of crystalline and amorphous forms of the drug, transitions between phases, polymorphism, and hydration. With respect to transport, the major effect of each of these properties is on the apparent solubility, which then affects dissolution and consequently transport. There is often an opposite effect on the stability of the material. Generally, highly crystalline substances are more stable but have lower free energy, solubility, and dissolution characteristics than less crystalline substances. In some situations, this lower solubility and consequent dissolution rate will result in reduced bioavailability. 

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