Sub Topic | Secondary Topic: Analytical Methodology - Non-biological Matrix | HPLC (Small Molecule)
Authors: Kaito Sakaguchi, TOWA Pharmaceutical Co., Ltd. (Presenting Author); Hitoshi Uchiyama, TOWA Pharmaceutical Co., Ltd.; Yasuhiro Sakakibara, TOWA Pharmaceutical Co., Ltd.; Hidehisa Tachiki, TOWA Pharmaceutical Co., Ltd. (Main Author)
Presenting Author: Kaito Sakaguchi
Purpose: Dysphagia and elderly patients are at risk of swallowing trouble when an oral medicine is not carried out appropriately into stomach. To avoid swallowing trouble, grinded tablet and opened capsule drug is prepared for dysphagia and elderly patients depending on the situation. Infant patients are often prescribed oral solution drug because infant patients simply unable to swallow conventionally-sized tablets. In addition, an oral solution drug mixed with other oral solution drug is prepared for infant patients depending on the situation. Because these dosage and administration did not approve by regulatory authority, stability and variability for these preparation of medicines are not well known. In general, high performance liquid chromatography (HPLC), such as reversed-phase chromatography is selected to determine the active pharmaceutical ingredient (API) in drug product for drug stability and variability. HPLC is difficult to establish an appropriate separation method for analysis of various components because of its physical property. Supercritical fluid chromatography (SFC) is characterized as a system using mainly carbon dioxide for mobile phase under supercritical conditions. SFC is regarded as enabling time efficient and cost effective in comparison to HPLC. But SFC gained only acceptance in narrow application area, such as preparative chromatography because of poor reproducibility and poor manageability. In recent years, new developments in SFC instrument could solve these problems. However, there are few reports to compare quantitative analysis of HPLC and SFC. We thus investigated each utility in SFC and HPLC method developments to evaluate drug stability and variability for after-grinded tablet drug, after-opened capsule drug and mixed oral solution drugs.
Methods: To evaluate drug stability for grinded tablet and opened capsule, grinded tablets of oxatomide (OXATOWA TABLETS 30mg, Towa Pharmaceutical Co., Ltd., osaka, Japan) and opened capsules of ubidecarenone (UBIDECARENONE CAPSULES 5mg TOWA, Towa Pharmaceutical Co., Ltd.,) were preserved under non-controlled temperature and humidity with lighting or shading condition. Each API in initial and preserved samples were analyzed by HPLC and SFC. To evaluate drug stability and variability of for mixed oral solution drugs, oral solution of aripiprazole (ARIPIPRAZOLE ORAL SOLUTION TOWA, Towa Pharmaceutical Co., Ltd.,) were mixed with oral solution drugs. Then they were preserved under controlled or non-controlled temperature and humidity with lighting or shading condition. API in initial and preserved samples were measured by HPLC and SFC. HPLC systems used for analysis were LC-2010HT (SHIMADZU Corp., Kyoto, Japan), Prominence UFLC (SHIMADZU Corp.), and ACQUITY UPLC H-Class System (Waters Corp., Milford, MA, USA) on ODS column. SFC system used for analysis was ACQUITY UPC2 System (Waters Corp.) on Torus 2-PIC column (Waters Corp.).
Results: In this study quantitative results of SFC were similar to HPLC, and the difference between the value of SFC and HPLC was not greater than 1.3%. In comparison to the analytical time, SFC analytical time was same and less than HPLC analytical time, for example analytical time of SFC (8 min) versus HPLC (8 min) for tablets of oxatomide, and analytical time of SFC (6 min) versus HPLC (14 min) for oral solution of aripiprazol. Since samples were containing several compounds expect for API in a drug mixture, it was generally assumed that the chromatogram of API is commonly affected by interference peak. In comparison to the resolution between interference peak and API peak of HPLC and SFC, almost all of chromatogram showed that resolution of SFC was poorer than that of HPLC (for example, resolution of SFC and HPLC was 3.1 and 5.5, respectively). The resolution of SFC was poorer than HPLC, but analytical time of SFC was shorter than that of HPLC by complete separation peak (resolution of necessity; more than 1.5).
Conclusion: This study showed that analytical time and resolution of SFC was equal or higher than that of HPLC in quantitative tests. Moreover, quantitative results of SFC were similar to those of HPLC. Since carbon dioxide as mobile phase of SFC are lower cost than methanol or acetonitrile as that of HPLC, SFC may have an advantage in running cost than HPLC. Therefore, utility of SFC may be equal or higher than that of HPLC. We hope SFC have the advantage of short drug development times through this results.
See attached abstract pdf for images.