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Abstract: Objective Study of bupropion hydrochloride gel matrix sustained release tablet and the preparation method, test the skeleton material of hydroxypropyl methyl cellulose influencing drug release for evaluation, explore the preparation of sustained release tablets of optimization method. Method With hydroxypropyl methyl cellulose as skeleton material, according to the different prescription preparation of bupropion hydrochloride sustained release tablets. Different HPMC viscosity, Consumption, particle size, compression pressure and slurry rotational speed and other factors, analysis the influence on drug release rate.Through the release of test evaluation of sustained release effect, and the preliminary study on the drug release characteristic. With hydroxypropyl methyl cellulose ( HPM
Key words: Pharmacy; hydrochloride bupropion; Hypromellose Cellulose.
HPMC will encounter water to form a gel layer, drugs, primarily through the dissolution of the gel layer diffusion and gel release from matrix tablets. Each drug has a different solubility, HPMC matrix tablets release mechani and influencing factors are not the same.
It has properties of the emulsifying, thickening, suspending, thickening, adhesion, film formation, etc., in the pharmacy, it is used for adhesives, dispersion agents, thickeners, film coating materials. In recent years, HPMC is more and more used in the study of the matrix tablets. The preparation process of the HPMC matrix tablets are convenient, simple, sustained-release effect ,HPMC materials has attracted the more and more attention.
In this study, on the basis of single factor, Prepared hydrochloride bupropion sustained release tablets, Analysis of the influence of HPMC on drug release factors, and explore the safety of hydrochloric bupropion sustained release tablets prepared by optimization method.
1.1 Hydrochloride bupropion sample preparation
That take prescriptions drugs and HPMC, citric acid, magnesium stearate and other accessories (over 150 μm sieve), after mixing them, using the pressed powder pellet craft. Because of the bigger size, good mobility accessories to improve the mobility of the medicines powder, the application of direct compression tablets method was better homogeneity of the medicines particles, and between all differences, within-batch reproducibility. The application of direct compression tablets can be obtained the hydrochloric security bupropion sustained release tablets.
Binder selection should be paid to the choice of high viscosity adhesive, adhesive ability to rely on powder sticky synthetic soft material. Reduce the moisture content of the adhesive. Using the adhesive with a high moisture content of low alcohol content, To prevent moisture stimulate the viscosity of the HPMC.
Preparation of hydrophilic gel sustained-release tablets, should ch
The experimental results show that, K models and its viscosity aller varieties of hydration effect more quickly, forming a gel quickly dissolved, also quickly. K type viscosity greater variety, hydration and more slowly, forming a gel is slower, but the gel is not easy to melt. Bupropion hydrochloride sustained release tablets release rate with HPMC viscosity increase slowed. According to the prescription requirements, this experiment chooses HPMC K100M for bupropion hydrochloride sustained release tablets of skeleton material.
The experimental results show that, with the increase of the content of K100M HPMC, the drug release rate slows down, at the HPMC K100M dosage is bigger, the drug release more slowly, with the main medicine quality ratio is 1 : 1, is the ideal state of releasing effect. Therefore, selection skeleton material HPMC K100M and main drug quality ratio of 1:
Studies amphetamine ketone in addition to the treatment of depression, manic - depression is more effective than other antidepressants, bupropion hydrochloride sustained release tablets has become the disease, preferred drugs. The latest survey results show that in China, the incidence of depression rates as high as 3% -5%, the incidence of depression around the world will reach 10% of the total population. Depression common diseases in the world ranked fourth, in China each year 200,000 people end their lives by suicide, of which 80% of suicide victims suffer from depression.
Hydrochloride bupropion is a unique amino ketones antidepressants. The drug does not directly affect the content of 5 - HT, is also different from the current widespread use of 5 - hydroxytryptamine inhibitor, does not inhibit monoamine oxidase, but play an antidepressant effect of norepinephrine and dopamine reuptake inhibition, the drug also has the role of oking cessation. Because of Complex fused ring structure, do not exhibit anticholinergic and monoamine oxidase inhibition. Thus without the side effects of the peripheral nervous system and autonomic nervous system. Compared with other antidepressants, few cardiovascular adverse reactions, and thus particularly suitable for elderly patients with long-term use. Because bupropion unique mechani of antidepressant effect, there is no adverse effects of antidepressants common sexual dyunction and weight gain. Studies he shown that hydrochloride bupropion release tablet rapidly absorbed. And rapid onset, within 7 days of treatment showed antidepressant activity, significantly reduced depressive symptoms.3.2 Skeleton material HPMC on bupropion hydrochloride sustained-release tablets significance
HPMC has many other materials do not he the characteristics. Hing excellent cold water soluble, just add it in cold water, a little mixing can be dissolved into a transparent solution, rather than 60E hot water is substantially insoluble, can only be dissolved. Is a nonionic cellulose ether, its solution with ionic charge, not with the metal salt or ion organic compound effect, so as to ensure the HPMC in preparation production process and other raw materials reaction. With strong resistant, and along with the molecular structure of substituted degree increasing, resistant also enhanced, using HPMC as auxiliary medicines, compared with other traditional materials ( starch, dextrin, powdered sugar ) drugs, its effective period more stable quality. Metabolically inert, as medicinal materials, are not metabolized, can not be absorbed, so the medicine food does not provide heat, on diabetic patients with lower heat value, without changing the original salt, medicine food has a unique applicability.
HPMC on acid and alkali is relatively stable, but if exceed pH2 ~ 11 and at the same time by the higher temperature and longe
The use of HPMC skeleton material can improve the dissolution. After the research, using HPMC ethanol solution or water solution as granulation with a wetting agent, to increase the dissolution of tablets, has a significant effect, and the pressed film hardness is good, ooth appearance. HPMC ethanol solution and water solution with improved drug dissolution effect, this is mainly because the HPMC has a suspending and surface activity effect, reduce the solution and the solid substance between the surface tension, increase the moisture, which facilitates the drug dissolution.
The use of HPMC skeleton material can increase the coating quality. HPMC as a film forming material, and other film-forming materials (acrylic resin, polyvinyl pyrrolidone), the biggest advantage is its water solubility, needs no organic solvent, safe operation, convenient. And the HPMC has a variety of viscosity specifications, selection of proper, coated tablets; appearance quality is superior to other materialsAs mentioned above, the use of HPMC as bupropion hydrochloride sustained release tablets of skeleton material benefit. At the same time, increased drug safety and stability.
References
1.Huafang Li, Niu Fan Gu. Antidepressant clinical application [J] Chinese Journal of clinical pharmacology and therapeu
2. Jiyue Chen, Hui Xu, Jianfang Zhang. Discussion of sustained release preparation time of dissolution test [J ] Chinese Journal of industrial medicine, 1991, (02).
3. Zhichao Dong, Xuetao Jiang. The physical properties of hydroxypropyl methyl cellulose on oral skeleton type preparation release effect, foreign medicine. Synthetic medicine biochemical medicine formulations. Fascicle 1995, (02)
4. Bo Wang, Laihua Zhang, Yuanxin Li, Shengshan Zhu. A hydrophilic gel matrix sustained release tablets release mechani research progress ofthe evaluation methods [J]. China Journal of pharmaceutical industry, 2009, (10).
5. Yuhua Dan. Hydroxypropyl methyl cellulose (HPMC) in tablet production application [J]. Qilu pharmaceutical, 2004, (02)
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C ) as skeleton material, with citric acid citrate as a porogenic agent, direct powder tabletting method of bupropion hydrochloride sustained release tablets; by using single factor and orthogonal experiment method to investigate HPMC different viscosity, different Consumption, different particle size, different compression pressure, different pulp rotational speed and other factors on the release of delivery rate. Result Select HPMC-K100M for bupropion hydrochloride sustained release tablets of the skeleton materials; reinforcing materials of high viscosity HPMC K100M and main drug quality ratio of 1: 1; HPMC particle diameter of 125μm, make use of these conditions to preparation of bupropion hydrochloride sustained release tablets for optimal prescription conditions. Conclusion bupropion hydrochloride sustained release tablets on the drug release rate is mainly affected by HPMC viscosity and dosage effect. Along with the tablet of HPMC viscosity increased, the drug is released slowly. HPMC viscosity, dosage on the drug release rate has significant influence.Key words: Pharmacy; hydrochloride bupropion; Hypromellose Cellulose.
1 Materials and methods
The pharmaceutical excipients is an important part of pharmaceutical preparations, whose role is to ensure that drugs for certain methods and procedures to selectively delivered to the tissues of the drug in the body at a certain pace and timing of the release. to choose the appropriate accessories is one of the key factors that play the efficacy of pharmaceutical preparations. The pharmaceutical excipients hydroxypropyl methylcellulose (HPMC) is one of the domestic and international the largest amount of pharmaceutical excipients of HPMC is often used as a film-forming agent, adhesives, release agents, suspension, emulsifier, disintegrantand so on.Hypromellose other names are Hydroxypropyl methylcellulose,hydroxypropyl methyl cellulose and HMPC. Hypromellose is one of the most widely used excipient. It has been used as an excipient in oral tablet and capsule formulations, where, depending on the grade, it functions as controlled release agent to delay the release of a medicinal compound into the digestive tract. It is also used as a binder and as a component of tablet coatings.HPMC will encounter water to form a gel layer, drugs, primarily through the dissolution of the gel layer diffusion and gel release from matrix tablets. Each drug has a different solubility, HPMC matrix tablets release mechani and influencing factors are not the same.
It has properties of the emulsifying, thickening, suspending, thickening, adhesion, film formation, etc., in the pharmacy, it is used for adhesives, dispersion agents, thickeners, film coating materials. In recent years, HPMC is more and more used in the study of the matrix tablets. The preparation process of the HPMC matrix tablets are convenient, simple, sustained-release effect ,HPMC materials has attracted the more and more attention.
In this study, on the basis of single factor, Prepared hydrochloride bupropion sustained release tablets, Analysis of the influence of HPMC on drug release factors, and explore the safety of hydrochloric bupropion sustained release tablets prepared by optimization method.
1.1 Hydrochloride bupropion sample preparation
That take prescriptions drugs and HPMC, citric acid, magnesium stearate and other accessories (over 150 μm sieve), after mixing them, using the pressed powder pellet craft. Because of the bigger size, good mobility accessories to improve the mobility of the medicines powder, the application of direct compression tablets method was better homogeneity of the medicines particles, and between all differences, within-batch reproducibility. The application of direct compression tablets can be obtained the hydrochloric security bupropion sustained release tablets.
1.2 Drug Release for testing standards
According to the Pharmacopoeia of the People's Republic of China in 2005 two Appendix Ⅹ C, a method, Take distilled water 1000 mL of release medium speed 50 r min-1, temperature (37 ± 0.5) ℃, , in 1,2,4,6,8,10,12 h to remove 7 mL sample respectively, At the same time complement plus an equal volume of water. Through 0.8 μm membrane filtration, the sample was discarded early filtrate, take continued the filtrate diluted with water of 15 mg · L-1 solution, as the test solution; Take an appropriate amount of bupropion hydrochloride sustained release tablets control samples, diluted with water to about 15 mg L-1 solution as a control solution, Measured absorbance at a welength of 251 nm to calculate the release amount of different times. The samples were 1, 2, 4,6,8,10,12 hour erage release amount源于：标准论文格式www.udooo.com
is 28%, 40%, 59%, 71%, 80%, 89%, 99%.2 HPMC Factors Influencing2.1 Viscosity
With the concentration and molecular weight increases, the viscosity of HPMC increased, at the same time, the temperature rises, HPMC viscosity began to drop, to a certain temperature, a sudden increase in viscosity and gelation occurs, the low viscosity type of gel temperature than the high viscosity typethe gel temperature. HPMCsolution is stable at room temperature and, in addition to HPMC could be enzymatic degradation, the general viscosity has no degradation phenomena.It has special thermal gelation properties, good film forming properties and excellent surface activity.Binder selection should be paid to the choice of high viscosity adhesive, adhesive ability to rely on powder sticky synthetic soft material. Reduce the moisture content of the adhesive. Using the adhesive with a high moisture content of low alcohol content, To prevent moisture stimulate the viscosity of the HPMC.
Preparation of hydrophilic gel sustained-release tablets, should ch
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oose large viscosity model, when necessary need to join the all viscosity model, to regulate the rate of release. At 20 degrees C, take the same amount of different viscosity HPMC ( F4M, E50, K4M, K15M, K100M ), according to the prescription and preparation process from sustained release tablets.The experimental results show that, K models and its viscosity aller varieties of hydration effect more quickly, forming a gel quickly dissolved, also quickly. K type viscosity greater variety, hydration and more slowly, forming a gel is slower, but the gel is not easy to melt. Bupropion hydrochloride sustained release tablets release rate with HPMC viscosity increase slowed. According to the prescription requirements, this experiment chooses HPMC K100M for bupropion hydrochloride sustained release tablets of skeleton material.
2.2 Consumption
Select HPMC K100M as skeleton material, selection of its and the main medicine quality ratio is 1 : 3, 1: 1, 3: 1, according to the formula and preparation technology of preparation of bupropion hydrochloride sustained release tabletsThe experimental results show that, with the increase of the content of K100M HPMC, the drug release rate slows down, at the HPMC K100M dosage is bigger, the drug release more slowly, with the main medicine quality ratio is 1 : 1, is the ideal state of releasing effect. Therefore, selection skeleton material HPMC K100M and main drug quality ratio of 1:
1.2.3 particle size
Selected particle size of 180 250 ~ m, 125 ~ 180 m, 125 m following HPMC K100M as skeleton material, according to the formula and preparation technology of bupropion hydrochloride sustained release tablets made. Experimental results show that, the HPM源于：科研方法与论文写作www.udooo.com
C particle size are different, the drug release rate changes a little. HPMC K100M decreasing the particle size, matrix tablets release rate also slowed down, but no significant impact, HPMC particle size from 125 to 180 M.2.4 compression pressure
With different pressure pressing tablet hardness respectively 5, 10 and 15KN, accumulative release percentage determination. The results showed that, in different tablet hardness, the drug release behior of almost the same. This is due to the pressure difference, the tablet hardness he the obvious difference, tablet porosity has bigger difference, but the HPMC hydration to form the gel layer porosity and initial porosity unrelated, causing compression pressure on HPMC skeleton in lesser affected drug release.2.5 paddle speed influence
Selections of propeller speed were 50R min-1, 100r min-1 and 1 50R min-1 prepared tablets determination of cumulative release percent. The results show that, the paddle speed on bupropion hydrochloride sustained-release tablets release almost no impact. This may be because the propeller speed does not affect the HPMC hydration layer of gel formation and bupropion in the gel layer release from..3 Discussion
3.1 Drug treatment significance of The hydrochloric An bupropionStudies amphetamine ketone in addition to the treatment of depression, manic - depression is more effective than other antidepressants, bupropion hydrochloride sustained release tablets has become the disease, preferred drugs. The latest survey results show that in China, the incidence of depression rates as high as 3% -5%, the incidence of depression around the world will reach 10% of the total population. Depression common diseases in the world ranked fourth, in China each year 200,000 people end their lives by suicide, of which 80% of suicide victims suffer from depression.
Hydrochloride bupropion is a unique amino ketones antidepressants. The drug does not directly affect the content of 5 - HT, is also different from the current widespread use of 5 - hydroxytryptamine inhibitor, does not inhibit monoamine oxidase, but play an antidepressant effect of norepinephrine and dopamine reuptake inhibition, the drug also has the role of oking cessation. Because of Complex fused ring structure, do not exhibit anticholinergic and monoamine oxidase inhibition. Thus without the side effects of the peripheral nervous system and autonomic nervous system. Compared with other antidepressants, few cardiovascular adverse reactions, and thus particularly suitable for elderly patients with long-term use. Because bupropion unique mechani of antidepressant effect, there is no adverse effects of antidepressants common sexual dyunction and weight gain. Studies he shown that hydrochloride bupropion release tablet rapidly absorbed. And rapid onset, within 7 days of treatment showed antidepressant activity, significantly reduced depressive symptoms.3.2 Skeleton material HPMC on bupropion hydrochloride sustained-release tablets significance
HPMC has many other materials do not he the characteristics. Hing excellent cold water soluble, just add it in cold water, a little mixing can be dissolved into a transparent solution, rather than 60E hot water is substantially insoluble, can only be dissolved. Is a nonionic cellulose ether, its solution with ionic charge, not with the metal salt or ion organic compound effect, so as to ensure the HPMC in preparation production process and other raw materials reaction. With strong resistant, and along with the molecular structure of substituted degree increasing, resistant also enhanced, using HPMC as auxiliary medicines, compared with other traditional materials ( starch, dextrin, powdered sugar ) drugs, its effective period more stable quality. Metabolically inert, as medicinal materials, are not metabolized, can not be absorbed, so the medicine food does not provide heat, on diabetic patients with lower heat value, without changing the original salt, medicine food has a unique applicability.
HPMC on acid and alkali is relatively stable, but if exceed pH2 ~ 11 and at the same time by the higher temperature and longe
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r storage time, will make the viscosity reducing. Water solution can provide surface activity, showing a moderate surface and interfacial tension of values. In a two-phase system with effective emulsifying effect, can be used as effective stabilizer and protective colloid. Aqueous solution has excellent film-forming properties, is a tablet, pill good coating material. It forms colourless, film has the characteristics of resilient. If adding glycerin, can also increase its plasticity.The use of HPMC skeleton material can improve the dissolution. After the research, using HPMC ethanol solution or water solution as granulation with a wetting agent, to increase the dissolution of tablets, has a significant effect, and the pressed film hardness is good, ooth appearance. HPMC ethanol solution and water solution with improved drug dissolution effect, this is mainly because the HPMC has a suspending and surface activity effect, reduce the solution and the solid substance between the surface tension, increase the moisture, which facilitates the drug dissolution.
The use of HPMC skeleton material can increase the coating quality. HPMC as a film forming material, and other film-forming materials (acrylic resin, polyvinyl pyrrolidone), the biggest advantage is its water solubility, needs no organic solvent, safe operation, convenient. And the HPMC has a variety of viscosity specifications, selection of proper, coated tablets; appearance quality is superior to other materialsAs mentioned above, the use of HPMC as bupropion hydrochloride sustained release tablets of skeleton material benefit. At the same time, increased drug safety and stability.
References
1.Huafang Li, Niu Fan Gu. Antidepressant clinical application [J] Chinese Journal of clinical pharmacology and therapeu
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tics, 2005, (08).2. Jiyue Chen, Hui Xu, Jianfang Zhang. Discussion of sustained release preparation time of dissolution test [J ] Chinese Journal of industrial medicine, 1991, (02).
3. Zhichao Dong, Xuetao Jiang. The physical properties of hydroxypropyl methyl cellulose on oral skeleton type preparation release effect, foreign medicine. Synthetic medicine biochemical medicine formulations. Fascicle 1995, (02)
4. Bo Wang, Laihua Zhang, Yuanxin Li, Shengshan Zhu. A hydrophilic gel matrix sustained release tablets release mechani research progress ofthe evaluation methods [J]. China Journal of pharmaceutical industry, 2009, (10).
5. Yuhua Dan. Hydroxypropyl methyl cellulose (HPMC) in tablet production application [J]. Qilu pharmaceutical, 2004, (02)