| Summary: | 碩士 === 中國文化大學 === 應用化學研究所 === 88 === Abstract
In-vitro drug dissolution provides an easy, economic and
effective approach to evaluating bioavailability. With the
selection of a pertinent dissolution method, drug dissolution can preliminarily replace the expensive in-vivo drug absorption test.
However, drug dissolution is under the influence of a variety of factors, such as the physical and chemical properties of drug materials, including particle size, polymorphs, solvate, and water solubility, and drug dosage form, including formulation and preparation method.
This study selected an anti-inflammatory agent - Piroxicam as study target. Piroxicam has analgesic and antipyretic actions and is prescribed once a day. It is chosen for its practical insolubility in water and the fact that different preparations by various manufacturers produce different dissolution.
First of all, five different raw material samples were obtained from the local importers and subjected to examination by the following instruments:
FTIR was used to test the samples and the standard provided by the National Laboratory of Foods and Drugs. It is found that all samples had similar wave number as that of the standard, except for Medichem which was inconsistent with the standard at several spots. Thus except for the raw material used by Medichem, all other materials probably have the same crystal form as the standard.
In DSC (Differential Scanning Calorimeter) test, samples were maintained at the same temperature and graphed by caloric differential against the temperature. It is found that the graphs of various samples were not markedly different from that of the standard, and thus unable to verify that any raw material has different polymorphs or solvate.
TGA (Thermogravimetric Analyzer) was employed to document the change of sample mass with temperature change. It is found that the samples showed no mass reduction at around 100C. The curves of various samples were similar, showing little variation in residue amount at 350C. The residue might be unignited sulfur (the boiling point of sulfur is 446 C).
Under the examination of Bright/Darkfield Polarizing Microscope, the comparison of 50X, 100X, 200X, and 500X optical photos and 50X and 200X polarized photos indicate that samples have marked difference in crystal form and particle size.
The scan of Laser Diffraction Particle Size Analyzer displays significant difference in the particle size and distribution of samples.
In terms of preparations, different raw materials were made into hard capsules using different formulations and preparation methods. The dissolution of various samples was tested by dissolution tester. Results show that the greater the particle size, the lower the dissolution, and the dissolution of pulverized samples were enhanced.
This study finds that the dissolution of drugs made of raw materials from different manufacturers varies significantly. Using different instruments to test the physical and chemical properties of various materials as described above, it is found that such variation might be a result of different particle size, whereas the polymorphs and solvate of the material have no bearing on dissolution.
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