Studies On Analyzers And Procedures For Evaluation Of Quality Of Drugs

Part A Study on the development of dissolution testanalyzerDrug dissolution is the dissolve rate and percentage of drugsfrom tablets or capsules in stated solution under a certain condition. Itis a in vitro experiment to simulate the drug dissolution ingastrointestinal tract, so it is an important test to evaluate drugbioavailability. In 1968, the dissolution test method of orphenadrinecitrate tablets was adapted by British Pharmacopoeia(BP), since thenmore and more drugs were adapted by pharmacopoeia all of the world.Drug dissolution in vitro has become an important examinationcharacterizing the pharmaceutical quality of drugs. Since 1970s,experts all over the world have spent much time, and there have set upa series of methods. Consequently, some analyzers have beendeveloped based on these methods. Nowadays there are three kinds ofdissolution analyzer been on sold : paddle stirrers dissolution analyzer,rotary baskets dissolution analyzer and flow-through dissolutionanalyzer.The above three kinds of dissolution analyzer is being developedin our laboratory. The development process and the instrumentalperformance of the newly developed dissolution analyzer wasexpatiated in this part.The conception, the history background, the insignificance andthe application of dissolution test were discussed in the first chapter. Inorder to understand the content of this part clearly, the principle ofdissolution test and commonly used dissolution analyzer wasintroduced, at the same time, the merits and demerits of theseanalyzers were also systematically discussed in this chapter. Somesuccessful commercialized dissolution test were listed at the end ofChapter one.Chapter two and chapter three were the core content of Part A. Inchapter two, the research project of the dissolution analyzer based onthe Pharmacopoeia of the People's Republic of China was fullyexpatiated. This instrument possesses the virtue of high automation,low cost and good accuracy, especially it is very suitable for compositetablets. The analyzer consists of optical-detection system, automatedsampling system, mechanical stirring system and data processingsystem. The drug dissolved in the mechanical stirring system, then thesolution was induced into the automated sampling system, at the sametime the optical-detection system acquired data, then the data wasprocessed by data processing system. The performance and the factoraffect the drug dissolution were discussed in Chapter three such assample mass, stirring speed, sampling rate, the classes of solvent. Anartificial intestinal solvent containing polyvinyl alcohol (PVA) wasadapted to test drug dissolution, a better simulation result was obtainedcomparing to the artificial intestinal solvent without PVA. Some realsamples were determined and the results were satisfied.For paddle stirrers method and rotary baskets method recorded inthe Pharmacopoeia of the People's Republic of China, there are somedemerits. In order to remedy these demerits, a dissolution analyzerbased on flow-through method was developed. It was fully presentedin Chapter four. A study on the performance of this setup wasexpatiatedPart B study on the development of drug moleculeinteraction analyzer based on surface plasmon resonanceThe first surface plasmon resonance (SPR) sensor was developedin 1983 by Liedberg et al, Since then, the research and application ofSPR technology have shown extensive growth and gradually becomethe hot spot and research frontier in the biosensor field in the world.The most important characteristics of SPR sensor are its versatility andcapability in real time monitoring the association or dissociation ofbiomolecules on the surface of the sensor without the need forfluorescence or labeling of the biomolecules. These characteristicsmade the SPR technique an easy, convenient and reliable one fordetermining the concentration and molecular weight, monitoringchange in structure, measuring kinetic constant and binding specificityof individual biomolecules. For above reasons the SPR sensors growas a new powerful technology in chemical and biological field.Several couplers in the SPR sensors have been employed. Theseinclude fiber optic SPR sensor, grating-based SPR sensor andprism-based SPR sensor. Based on detection mode, the SPR sensorsinclude angle modulation, polarization state modulation, intensitymodulation, phase modulation and wavelength modulation. Thesesetup were fully discussed in Chapter five. At last some successfulcommercialized instrument were listed.In chapter six, a novel optical chemical sensor was developed.Traditionally, wavelength modulation SPR sensing method was to usetungsten lamp as light source which needed an expensive andcomplicated apparatus. The device presented here is a relatively simpleand inexpensive. It was designed using white LED as light source, andlightened by a 5V battery. The setup consisted of white LED, lighttransmit system, sensing element, flow cell, detection system and datadealing system. The SPR sensor was designed on the basis of fixingthe angle of incident light and measuring the change of resonantwavelength. The light emitted from the white LED is polarized to giveTM polarized light, and two lenses are employed to make the lightparallel. The parallel polychromatic light beam passes through anoptical prism with a thin gold film on the bottom and excites surfaceplasmon at the interface between the gold film and solution. Theoutput light from the prism is guided into a charge coupled device(CCD) detector by fiber. The data acquired by CCD was processed bydata processing system.The interactions between drug and protein were presented inChapter seven. First the binding rate of antibiotics and protein wasstudied by this apparatus. Eight antibiotics were analyzed with thesensor. Then results were compared with the reliable binding-rate datamade by standard equilibrium dialysis. The results of comparison arein good relationship and it can be used to determinate the binding rateof antibiotics and protein. At the end of this chapter, Based on SPR, anovel optical chemical sensor for distinguishing enantiomeric drugswas developed. The difference between combination reaction ofenantiomeric drugs with albumins was studied by using this setup.According to these differences the enantiomeric drugs can bedistinguished. The method was shown to have many advantages overtraditional methods. The major ones include the elimination of labelingand screening rapidly.