Uniformity of dosage unit

Additional detection techniques that can be employed to help solve mass balance issues with RP-HPLC are MS [30], chemiluminescent nitrogen-specihc detector [31], evaporative light-scattering detector, ELSD [32], and corona charged aerosol detection [CAD] [33], 

Some degradation products are either very polar or very nonpolar in nature this may present an issue in chromatography, where they may not be retained or strongly adsorbed on the column, respectively. One may also want to double check the reference standard for its purity, moisture content, and/or salt/ acid-base ratio for calculation. An analytical chemist must remember to explore all possibilities if mass balance issue is observed (either during method development, validation and/or stability testing). 

The following four steps have been proposed by Bakshi and Singh for a development of a SIM [34] (1) critical study of an API to assess the likely decomposition route(s), (2) collection of information on physicochemical properties, (3) stress (forced decomposition) studies, and (4) preliminary separation studies on stressed samples. 

However, a SIM during formulation development involves more than the above four steps, since the formulation development is a dynamic process where the formulation is optimized as the clinical program moves further along the development process. To continue the list from above, the following three steps must be added to the Ust (5) compatibility studies with excipients, (6) stability trending (variables would be temperature, humidity, and packaging material), and (7) mass balance for assay. An analytical chemist must revisit the separation of all components in the related substances method after steps 3,5, and 6 to ensure that the test method is truly a SIM. 

In addition, HPLC can be employed as a reference method for unknown degradation products where an unknown degradation product can be identified based on its the retention behavior in RP-HPLC and the corresponding relative retention time is determined (retention of degradation product/reten-tion of API). 

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It is shown, that for assay of substances and prepai ations the different approaches ( Confirming and Inspecting ) should be applied. The criteria to analytical procedures uncertainty for tests Uniformity of dosage units and Dissolution ai e developed. 

Uniformity of dosage units. When the test is carried out as directed in the general procedure <905> meet the requirements. 

The Q6A and Q6B documents were preceded by the North American Conference on Specifications. In all cases, no method selection, scope of application, or overall policy (dissolution, impmities, particulate matter, etc.) is at odds with USP, a remarkable condition in view of the breadth of the topics covered. The main difference is the proportion of active ingredient in a formulation that triggers choice of determination of content or of weight to establish Uniformity of dosage units. 

If the results pass these criteria and the adequacy of mix and uniformity of dosage unit content for the batch are adequate, the SCM can be used for the next batch. If test results fail stage 1 criteria, extended testing to stage 2 is required. 

Uniformity of dosage units Content uniformity Weight variation... 

Pharmacopeial Forum, Harmonization, General Chapter <905> Uniformity of Dosage Units. Pharm Forum 2001, May-June, 27 3) 2615—2619. 

T. Beckert, K. Lehmann, P. C. Schmidt, Compression of enteric-coated pellets to disintegrating tablets Uniformity of dosage units, Powder Tech 96 248-254 (1998). 

Postgranulation mix time Uniformity of dosage unit Compression profile Dissolution profile... 

Can API be Micronized The particle size of drug substance at the micron level is critical to achieving blending uniformity and uniformity of dosage unit.16,17 If the drug substance cannot be micronized due to physicochemical stability or material properties, consider dissolving the dmg in solution for forwarding processes. 

United States Pharmacopeia. 2007. <905> Uniformity of Dosage Unit. 30-NF 25. 

Figure 18.1 Schematic description of content uniformity of dosage unit.

The term uniformity of dosage units (UDUs) is defined as the degree of uniformity in the amount of the active substance among dosage units [35]. The UDUs can be demonstrated by either of two methods content uniformity (CU) or mass variation (MV). Mass variation can be utilized for drug... 

European Pharmacopeia, Uniformity of dosage units. Chapter 2.9.40,2005. 

The BUWG called for data from pharmaceutical companies to verify the acceptance criteria stated in the FDA s draft guidance. Computer simulations were used, alongside the acquired data to test the hypothesis blend imiformity testing in routine manufacture is not predictive of the uniformity of dosage units. Using... 

The required specification for this test is that uniformity of dosage unit should be within a range of 85%-115% with a relative standard deviation of less than or equal to 6%. 

The United States Fliaimacopeia, 29th Revision, <90S> Uniformity of Dosage Units. The United States Pharmacopeial Convention. Rockville, MD. 2(X)6 2778-9. 

Byron PR, et al. Recommendations of the USP advisory panel on aerosols on the USP general chapters on aerosols [601] and uniformity of dosage units [905]. Pharm Forum 1994 7 7477-7503. http //www.fda.gov/cder/guidance/index.htm. 

Uniformity of dosage units. This test includes uniformity of both content and mass. 

Uniformity of dosage units. Generally, acceptance criteria should be set for weight variation, fill volume, and/or uniformity of fill. For powders intended for reconstitution, uniformity of mass testing is generally considered acceptable. 

What about the capability of the process to meet the USP Uniformity of Dosage Units requirement A technique useful in this area is process capability analysis. The relationship between the spread or variability of a process and the specifications imposed on the process is defined by the process capability. Define process capability, Cp, by Eq. (8) ... 

Nasal sprays with a declared amount of active substance for each puff (so called metered-dose sprays), should comply with the requirements on the variation in this amount. In practice, this is only seen in licensed medicines. For solutions the test for uniformity of mass is sufficient. Suspensions should comply with the test for uniformity of dosage units (see Sect. 32.7.2.4), or, where justified and authorised, with the test for uniformity of delivered dose. In this test, specially meant for metered-dose sprays, the allowed range of variation is much broader than for oral preparations. 

Parenteral solutions are to be tested for absence of visible and non-visible particles and sterility as specified in the Ph. Eur. Furthermore, freedom from pyrogens or endotoxins and the uniformity of dosage units and content are stipulated (see Sect. 32.8). Suspensions should be easily resuspendable to ensure precise dosing and uniformity of the dose during administration. Parenteral emulsions should be homogeneous. 

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