Research on the Influence of HPMC Release the Bupropion Hydrochloride Sustained Release Tablets.doc

1、1Research on the Influence of HPMC Release the Bupropion Hydrochloride Sustained Release TabletsAbstract: 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 f

2、or 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

3、, 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

4、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 si

5、ze, different compression 2pressure, 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 r

6、atio of 1: 1; HPMC particle diameter of 125m, 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 viscosi

7、ty 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

8、 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 3one of the key factors th

9、at 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, emuls

10、ifier, 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 functio

11、ns 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

12、from matrix tablets. Each drug has a different solubility, HPMC matrix tablets release mechanism 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 a

13、gents, 4thickeners, 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

14、 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 preparati

15、on That take prescriptions drugs and HPMC, citric acid, magnesium stearate and other accessories (over 150 m 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 dir

16、ect compression tablets method was better homogeneity of the medicines particles, and between small 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 sta

17、ndards 5According to the Pharmacopoeia of the Peoples Republic of China in 2005 two Appendix 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 volum

18、e of water. Through 0.8 m 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 a

19、bout 15 mg L-1 solution as a control solution, Measured absorbance at a wavelength of 251 nm to calculate the release amount of different times. The samples were 1, 2, 4,6,8,10,12 hour average release amount is 28%, 40%, 59%, 71%, 80%, 89%, 99%. 2 HPMC Factors Influencing 2.1 Viscosity With the conc

20、entration 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 ge

21、l temperature. HPMC solution is stable at room 6temperature 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

22、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

23、of hydrophilic gel sustained-release tablets, should choose large viscosity model, when necessary need to join the small 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 a

24、nd preparation process from sustained release tablets. The experimental results show that, K models and its viscosity smaller 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 slowe

25、r, but the gel is not easy to melt. Bupropion 7hydrochloride 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 Cons

26、umption 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 tablets The experimental results show that, with the increase of

27、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.

28、 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 HPMC particle size are different, the

29、 drug release rate 8changes 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, accumul

30、ative release percentage determination. The results showed that, in different tablet hardness, the drug release behavior of almost the same. This is due to the pressure difference, the tablet hardness have the obvious difference, tablet porosity has bigger difference, but the HPMC hydration to form

31、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

32、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 93.1 Drug treatment significa

33、nce of The hydrochloric An bupropion 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

34、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 suf

35、fer 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

36、 of norepinephrine and dopamine reuptake inhibition, the drug also has the role of smoking 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.

37、 Compared with other 10antidepressants, few cardiovascular adverse reactions, and thus particularly suitable for elderly patients with long-term use. Because bupropion unique mechanism of antidepressant effect, there is no adverse effects of antidepressants common sexual dysfunction and weight gain.

38、 Studies have 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 h

39、as many other materials do not have the characteristics. Having 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 solut

40、ion 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 )