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Calorimetry And Thermal Analysis Studies On Thermodynamic Properties Of Drugs

Posted on:2006-03-14Degree:DoctorType:Dissertation
Country:ChinaCandidate:F XuFull Text:PDF
GTID:1101360155952355Subject:Physical chemistry
Abstract/Summary:PDF Full Text Request
Thermodynamic characteristics of 28 drugs including (+)-ibuprofen,(±)-ibuprofen, caffeine, theophylline, aminophylline, acetaminophen, aspirin etc.,were systematically studied, by combining high precision adiabatic calorimetryand modern thermal analytic techniques. The molar heat capacities and phasetransition temperatures of these drugs were measured with a high precisionadiabatic calorimeter; the enthalpies, entropies of phase transitions, thethermodynamic functions (relative to the standard state at 298.15 K) werecalculated for these drugs based on the heat capacity data. Thermal kineticparameters for the evaporation or decomposition process of these drugs and theirthermal stabilities were evaluated through differential scanning calorimetry (DSC) andthermogravimetry (TG). The standard formation enthalpies of some drugs weredetermined by means of the combustion calorimetry. The research work of this thesisfilled the blank of the thermodynamic property data of these drugs. Thesefundamental data will increase our understanding about these drugs and be helpfulto the design of industrial devices, the control of processes and refinement ofproduction conditions concerned with these important drugs.Quantum chemistry calculation was used for prediction of thermaldecomposition mechanism of aspirin drug in the light of its bond order for the firsttime in the thesis. The decomposition reaction path of aspirin drug was deducedaccording to the calculated bond order. The decomposition mechanism of aspirinobtained in terms of quantum chemistry calculation is in fine agreement with thatgained from thermogravimetry experiments. Hence, it is feasible to use quantumchemistry calculation for study of thermal degradation of drug. The stability of drug and its dosage is of great importance for prediction ofits efficient storage duration. Traditional methods are really time consuming. Theresearch efforts at present are mainly focused on finding an easy way for thispurpose. In this thesis, thermal analyses for about 21 drugs were performed. Theresults obtained show that there is a correlation between pk (i.e. negativelogarithm of rate constant of decomposition/evaporation process) and efficientstorage duration of drug. What this thesis would like to point out is that the initialthermal decomposition temperature of principal components in drugs should beconsidered except pk, in order to determine the efficient storage duration of thedrugs. It is suggested that the efficient storage duration of the drugs should beclassified into the following 3 ranges in terms of their pk values and the initialtemperature of thermal decomposition; for range I (pk ≤7.0, and initialtemperature T ≤450 K), the efficient storage duration of drugs is between 1.5and 2 years; for range II (7.0 < pk ≤12.0, and initial temperature T > 450 K), theefficient storage duration of drugs is about 3 years; for range III (pk > 12.0, andinitial temperature T was not defined at present yet), the efficient storage durationof drugs is between 4 and 5 years. The efficient storage duration for differenttablets of vitamine B4, coronary heart disease, ciprofloxacin hydrochloride andvitamine B12 was predicted with the established model as mentioned above, and itis in good agreement with that on its label. Therefore, the thermal analysistechniques utilized in the thesis can be used for prediction of efficient storageduration of drugs. The isothermal microcalorimetry was used for systematic studies ofinhibition function of 4 antibiotics ( as ceftizoxime sodium,cefotaxime sodium,ceftriaxone sodium and benzylpenicillin sodium) to growth of escherichia coli, theefficacy of these drugs were accordingly evaluated. According to the experimentresults, the inhibition action order of these antibiotics was determined as follows:ceftizoxime sodium > cefotaxime sodium ≈ceftriaxone sodium > benzylpenicillinsodium. The research results are in agreement with those in clinic. It shows thatmicrocalorimetry is valuable for evaluations of efficacy of drugs or drugintermediates. It is also helpful for design and development of new drugs.
Keywords/Search Tags:drug thermodynamic property, efficient storage duration of drugs, thermal analysis, adiabatic calorimetry, combustion calorimetry, microcalorimetry, quantum chemistry calculation
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