Dissolution testing HPLC methods

V. REQUIREMENTS OF HPLC METHODS FOR DISSOLUTION TESTING DURING DRUG DEVELOPMENT PROCESS... 

Development of efficient and reliable HPLC methods for dissolution testing can at times be problematic. Several factors need to be taken into consideration during method development. 

Despite the lack of inherent selectivity, it is still possible to obtain good quantitative data from online UV/vis monitoring by making use of chemometric techniques to resolve the overlapping spectra. The most common application is in dissolution testing [73, 74], where results that are at least as accurate as those of the reference (and much slower and more costly) HPLC method have been demonstrated. 

Purity and potency are two of the metrics that pharmaceutical quality assurance (QA) departments emphasize to determine if a batch may be released. To do this they typically employ HPLC and/or mass spectrometry to determine gross composition, and to verify the absence of any contaminants. However, only a small subset of tablets in a batch is tested because the tests destroy the sample. While these methods offer some insight into sample consistency, they provide no information on the distribution of the components in an individual finished form. Dissolution testing is used to indicate the manner and... 

The concentration profile during the dissolution testing of melphalan tablets in water and simulated gastric fluid was determined by HPLC. A method of data analysis was developed to take into account the spontaneous drug degradation [111]. 

HPLC methods are preferred if excipients would interfere, if nonspecific detection techniques (mainly in UV) would be used, or when multiple APIs (combination product) are present in a drug product. Since dissolution sample set analysis can be very long due to six samples per bath as well as multiple time points for prohle testing, fast run times are preferred to quickly determine the results. If a fast HPLC method for CU is available, then the identical HPLC method can be utilized for dissolution analysis. 

The stability testing requirements for diltiazem hydrochloride include an HPLC assay and dissolution test. The HPLC assay is described in the section for the potency assay (9.2.1.1.) and the dissolution test method is described in Section 9.1. 

This chapter reviews the use of HPLC in pharmaceutical analysis from drug discovery to quality control. The focus is on HPLC analysis of drug substances (DS) and products (DP) such as assay for potency, purity evaluation, and dissolution testing. A case study of the various HPLC methods used during early clinical development illustrates the versatility of this technique. Detailed descriptions of HPLC applications in pharmaceutical development and LC/MS analysis in drug discovery and bioanalytical studies can be found elsewhere.1-6 The regulatory aspects in pharmaceutical testing are covered in Chapter 9. 

Table 6.7. Typical Method Attributes for HPLC Methods for Dissolution Testing...

---