Gliclazide Solid Thermal analysis of melt
Author: Peng Hong Wang Lu Hua Xu Jun Zhao Defang
【Abstract】 Objective confirmed by thermal analysis of melt formation. Methods in accordance with differential scanning calorimetry (DSC) and thermal gravimetric analysis (TG) were measured lactose, gliclazide, as well as lactose and gliclazide samples mixed in different proportions. The results of DSC curve and TG curve that lactose and gliclazide formed under a certain percentage of a total melt. Conclusion lactose and gliclazide, under a certain percentage of the samples by high-speed grinding mixture formed a total of melt; using this technology can significantly improve the primary drug of insoluble drug gliclazide dissolution rate.
Key words gliclazide solid total melt DSC thermal analysis TG
AbstractObjectiveTo illustrate the preparation of Gliclazide dispersible tablets by thermoanalysis technology. MethodsTo determine Galactosylglucose, Gliclazide and the different proportion of Galactosylglucose and Gliclazide according to the methods of different scanning colorimetry (DSC) and mogravimetry (TG). ResultsFrom the graphs of DSC and TG, solid dispersion was formed in the procedure. ConclusionThe sample of Galactosylglucose and Gliclazide can
form solid dispersion by high speed grinding.The dissolution rate of Gliclazide can be significantly improved by this technology.
Key wordsGliclazide; Solid dispersion; DSC; TG
Thermal analysis in various fields of medicine widely
used, due to thermal analysis trace of a sample, fast and
easy, without separation of the sample, without solvents, application of a wide range of the curve the advantages of easy to parse . In pharmaceutical research and drug quality
testing, etc., thermal analysis techniques play an important role in , while the solid dispersion is to increase the drug dispersion, solubility, dissolution rate, improve the bioavailability of drugs is an effective method [3 ].
In this study, choose to cross-linked sodium
carboxymethyl cellulose and cross-linked polyvinylpyrrolidone
as a disintegrant, lactose and microcrystalline cellulose as filler designed to counter . The process will be Gliclazide of raw materials and auxiliary materials used lactose solid
dispersion technology, home high-speed milling machines,
grinding 1min or so, its grind the powder fine (through 200 mesh) in order to improve the insoluble drug glibenclamide Qi Special of the dissolution rate. Now on its thermal analysis
techniques were able to form solid melts to make the following research.
A thermal analysis
1.1 Differential scanning calorimetry (DSC)
1.1.1 Instruments and reagents Pyris / DSC scanner (U.S. PE company); lactose (Shanghai dairy products factory);
gliclazide (Tianjin Zhongxin Pharmaceutical Group, The New pharmaceutical).
1.1.2 conditions for heating rate 10 ? / min,
temperature range 50 ~ 250 ?, high-purity nitrogen measured
during the pass protection to a blank aluminum samples as reference, apparatus, high purity indium and zinc have been used as a benchmark material for temperature and heat
1.1.3 Methods According to the ratio in the sample listed in Table 1 DSC thermal analyzer (DSC instrument), the determination of 1. Lactose; 2. Gliclazide; 3 ~ 10. Lactose, gliclazide different ratio of high-speed grinding mixed
samples. See Table 1 and Figure 1 ~ 4. Table 1 lactose, gliclazide and mixtures of the DSC curve (abbreviated)
1.1.4 Results from the DSC curves of lactose passes
gliclazide DSC curve we can see that lactose temperature-
programmed to 149.69 ? endothermic peak when, 153.43 ? end,
this peak for the crystallization of lactose water peak, 217.91 ? melting point for the lactose peak , 169.79 ? for
the melting point of gliclazide peak.
Lactose and gliclazide mixed in different proportions,
the system in the DSC curves of the melting point of gliclazide does not change with the composition of the system change, while the lactose peak temperature changes with composition to make the law change. Peaks with lactose melting point temperature of the vertical axis, lactose and gliclazide ratio of the horizontal axis, draw the eutectic temperature of the system - the composition of maps, the proportion of the available mixture system diagram. Figure 5.
Figure 5 shows that the melting point of lactose with a
larger proportion of gliclazide which in turn reduced, when X1 = 0.3, the basic overlap. Until X1 = Xe = 0.33 when the overlap as a single peak, so that the lactose and gliclazide formed a solid total of melt, this time, lactose: Greg Qi
specially designed for 2:1. The total melt and other accessories made of dispersible tablets of gliclazide by the quality and standards of inspection, content and related materials comply with the provisions describing the eutectic does not change the characteristics of drugs. Reposted
elsewhere in the paper for free download http://
1.2 Thermogravimetric analysis (TG)
1.2.1 Instruments and reagents DT-40 type differential
thermal analyzer (Shimadzu Corporation); lactose (Shanghai dairy products factory); gliclazide (Tianjin Zhongxin Pharmaceutical Group, The New pharmaceutical).
1.2.2 conditions for heating rate 10 ? / min,
temperature range 50 ~ 250 ?, flow of nitrogen atmosphere.
1.2.3 Methods listed in the samples tested in the thermal analysis instrument, 1. Lactose; 2. Gliclazide; 3. Lactose: gliclazide (2:1) according to method of high-speed milling
process mixed samples. The results shown in Figure 6 ~ 8.
1.2.4 The results of the TG curves can be seen from the
lactose, there are two weight loss peaks and the DSC exactly match, DSC first temperature of a heat-absorbing Fengfeng
149.7 ?, accompanied by TG weight loss peak (5.9%), for lactose molecule 1 water of crystallization corresponding to; DSC first two endothermic Fengfeng temperature of 217.9 ?,
accompanied by significant weight loss peak for the decomposition of lactose melting peak. Gliclazide by the TG curves can be seen, in the 160 ~ 300 ? has a significant
weight loss peaks, corresponding DSC curves, DSC curves for a endothermic peak, peak temperature 172.52 ?, shows TG weight
loss peak due to melting and decomposition. Mixed samples of two weight loss peaks, the first weight loss peak for a crystal water, 118.4 ~ 155 ?; the first two weight loss peaks
due to melting and decomposition of (160 ~ 296 ?), further
explanation lactose and gliclazide, under a certain percentage of the formation of a total melt.
2 dissolution rate test
2.1 Instruments and reagents Intelligent Dissolution Tester ZRS-8G (Tianjin University Radio Factory); Sample 1: gliclazide tablets (by prescription volume, conventional methods of preparation); Sample 2: gliclazide tablet (prepared
according to Formulation samples, batch 20,051,021).
2.2 The determination method according to dissolution assay. With phosphate buffer (pH7.4) 900 ml of solvent and rotational speed: 100 r / min, according to operation, 30 min
when the solution obtained filtered, sophisticated take 5 ml volume of 25 ml Liangping in the home, using phosphate-
buffered salt solution was diluted to scale, shake. Another take Gliclazide appropriate reference standards, using phosphate-buffered saline solution made of 8 μg / ml of the
solution, according to Pharmacopoeia spectrophotometry, the wavelength of 226 nm absorbance were measured to calculate the amount of each piece of the dissolution. Limit of 80% of the labeled amount, should meet the requirements.
2.3 Determination of the results of the dissolution rate of sample 2 was significantly higher than sample 1. Table 2. Table 2 Dissolution rate of Gliclazide experimental results (omitted)
These results indicate that lactose and gliclazide in a certain proportion of high-speed grinding of samples form a
solid mixture of the melt. Using this technology can significantly improve the primary drug of insoluble drug gliclazide dissolution rate.
In the pharmaceutical field, thermal analysis is to study the drug crystal form, purity, stability, interaction between drugs and excipients such issues as important means. This method of solid dispersion systems, and liposomes are also widely used. This experiment confirmed by thermal analysis of
solid total of melt formation.
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