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The dissolution properties of a drug determine its release profile to match the product specifications. All new drugs should meet current USP dissolution test requirements, Dissolution Testing should be performed in GLP-compliant laboratory. BioVolutions measures drug dissolution for both oral as well as topical formulations. For oral formulations, below saturation at 37ºC in water or aqueous based buffers (pH range of 1 to 7) in a dissolution apparatus under precisely controlled mechanical and operational parameters. Depending on the nature of the drug (and in accordance with a developed and validated protocol) the tests are conducted for various durations from 15 minutes to 24 hours with appropriate sampling. The results of the dissolution analysis are reported as cumulated percent drug dissolved at specified time intervals. For topical formulations, BioVolutions employs an in-line In Vitro Release apparatus to measure drug dissolution, especially for SUPAC for manufacturing compliance. BioVolutions’ drug dissolution studies are performed
in a GLP-compliant lab.
Because of the critical nature of the first two of these steps, in vitro drug dissolution is predictive of in vivo performance. Based on this general consideration, in vitro drug dissolution tests for immediate-release tablets and capsules and topical gels are used to:
Knowledge of the dissolution properties of a drug should be considered
in defining dissolution test specifications for the drug approval
process. This knowledge should also be used to ensure continued bioequivalence
of the drug, as well as to ensure the drug’s sameness under
scale-up and post-approval changes. Acceptable bioequivalence and
comparable in vitro dissolution data should submitted to
the FDA together with chemistry, manufacturing, and controls
(CMC) data to characterize the quality and performance of the
drug are required for FDA approval of new-drug applications
(NDAs) and abbreviated new-drug applications (ANDAs) (21 CFR 314.94).
The FDA’s Division of Bioequivalence may also request submission of additional drug dissolution testing data as a condition of approval, when scientifically justified. For further information, see Guidance for Industry: Dissolution Testing of Immediate Release Solid Oral Dosage Forms, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), August 1997.
BioVolutions Inc. develops and qualifies many types of analytical methods for its clients and the methods are tailored to project requirements. Typical analytical methods consist of two components: separation and detection. The majority of analytical methods used at BioVolutions are based on liquid chromatographic separation using common separation techniques. These include normal and reverse phase chromatography, ion-exchange chromatography and size exclusion chromatography. Several types of detectors are available such as UV or MS and their use is determined by properties of the analyte. In addition, BioVolutions offers ELISA method development for biological detection of proteins and peptides. BioVolutions offers analytical method development and validation which conform to both international and U.S. regulations. At your discretion, our scientists can either work with the data you provide or we can do our own analysis, using a small amount of your reference material.
A stability indicating method is necessary for a successful drug development program. BioVolutions develops and qualifies stability indicating methods based on HPLC/UV and HPLC-MS analytical techniques. In development of a stability indicating analytical method a separation technique is adapted to resolve the analyte of interest from impurities, degradation products, and excipients. The most common technique used for this purpose is liquid chromatography. Following ICH guidelines, Biovolutions will place the API or the product on accelerated stability at 40º C/75%RH for 6 months, medium-term stability at 30º C/65% RH for 9 months and long-term stability at 25º C/60% RH for 2 years. In addition, since pure samples of degradation products are rarely available, forced degradation studies are undertaken that mimic the degradation/decomposition of the drug substance under a wide range of conditions.
Particles are measured by laser diffraction technology over a wide size range, from 0.02-2000 mm, accurately and non-destructively, for both wet and dry dispersions. Our methodology broadly follows recommendations outlined in ISO13320-1, the international standard for laser diffusion. In particular, section 6.2.3 (Dispersion) is followed closely. In both wet and dry methods development the objective is to understand the effect of energy on the particulate system (distinguishing conglomerates from dispersed particles) in line with the needs of measurement outcomes (bulk or primary particle size). In a dry measurement, to assess both dispersion and the extent of attrition (if applicable), the material is subjected to what is called a “pressure-size titration” where the effect of increasing controlled energy input is examined (See Section 6.2.3.2 ISO 13320-1). Controlling the DP across the venture regulates this energy input. Shear processes by acceleration will (in theory) separate any agglomerates into primary particles. Increased energy can cause attrition of friable samples especially those that are organic or of high aspect ratio. For large samples then another consideration is that of carrying the particles through the measurement zone in the air stream and high flow rates are normally used for this. To ensure that we meet the needs of our customers in complying with the requirements of Regulatory Authorities such as the US Food and Drugs Administration (FDA), BioVolutions provides particle size measurements for products subject to FDA regulation, we have solutions to help with 21 CFR Part 11 compliance.
Please contact BioVolutions for additional information. |
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Copyright © Biovolutions, Inc. 2008
