片剂的制备 工业药剂

1、Department of PharmaceuticsSchool of PharmacyChina Pharmaceutical University2011-5-5PurposeIntroductionEquipments and MaterialsProceduresExperimental InstructionsQuestionsTest report Purpose 1. To master the basic technological course of tablets through the preparation of aspirin tablets.2. To be fa

2、miliar with the quality control of tablets.3. To be familiar with the basic structure and operation method of single-punch.Introduction Tablets are solid preparations of various shapes, usually round, and obtained by compressing uniform volumes of particles containing one or more active ingredients

3、with suitable excipients.Introduction - tablet typesSome of the pharmaceutical tablet types based on the way of administration or presentation to the patient are listed on the right:1. Simple uncoated tablets2. Coated tablets3. Effervescent tablets4. Buccal and sublingual tablets5. Chewable tablets6

4、. Multilayered tablets7. Sugarcoated tablets8. Fast-disintegrating tablets9. Vaginal tablets10. Osmotic tablets11. Controlled-release tablets12. Multicomponent tabletsIntroduction - tablet designTablet formulation design starts with a predetermined value, which is the dose size. Tablet design is bas

5、ed on the experience and knowledge of excipients, which are materials serving the purpose of making a good tablet when combined with a drug.Introduction - tablet designTablet excipients can be classified on the basis of their functionality as listed below:1. Fillers/diluents2. Binders3. Disintegrant

6、s4. Lubricants5. Glidants6. Buffering agents7. Sweeteners8. Wetting agents9. Coating agents10. Matrix formersIntroduction - manufacturing processesDeciding on a manufacturing method is a complex task that requires time, equipment, and formulation optimization, as well as a close collaboration betwee

7、n formulation scientists and process engineers. In general terms, there are three manufacturing processes for tablets: wet granulation, dry granulation, and direct compression.Introduction - manufacturing processesThe purpose of wet granulation is to convert the drug and excipient mixture into granu

8、les that flow well into dies, and which are compressible into mechanically strong and acceptable tablets. 1. flowability 2. compressibilityWet granulation compression method has been widely used in tablets production, especially for drugs resistant to wet and heat. Introduction - manufacturing proce

9、ssesThe steps of wet granulationPremixing drug with other ingredients using a mixer. Transferring the mixture into a traditional low shear granulator where a binder solution is added under a mechanical shear until a certain damp mass and a certain granule size are obtained.Wet sieving of granules th

10、rough a desired screen size.Drying of granules in a tray-oven dryer.Dry sieving/milling of granules to a certain particle size distribution.Adding a lubricant to the dry granules.Compressing the granules into tablets.Introduction - manufacturing processesThe steps of wet granulation 混合压片填充剂黏合剂崩解剂API

11、辅料粉碎和过筛制软材干燥整粒混合制湿粒润滑剂崩解剂湿法制粒压片工艺流程Introduction - manufacturing processesEquipments and MaterialsEquipments: electronic balance, single-punch press, nylon sieve (16 and 18 mesh), punch (9.5mm shallow concave punch), etc .Materials :aspirin (in granule crystal), tartaric acid, talcum powder, starch,

12、concentrated hydrochloric acid, sodium hydroxide, distilled water, etc.Procedure1. Preparation of aspirin tablets(1) Formulation (weight in 100 tablets)Aspirin30 gStarch 2 gTartaric acid 0.2 g10% starch paste qsStarch 1 gTalcum powder 1.5 g(2) Preparing processesPreparing 10% starch paste: Heating t

13、he aqueous dispersion of starch ( 2 g starch and 0.2g tartaric acid in 20mL water) at 80 for 15 min. Grinding aspirin to pass the sieve of 80 meshes. Mixing aspirin powder with starch.Adding 10% starch paste to prepare a damp mass. Screening the damp mass through a nylon sieve of 18 meshes into gran

14、ules. Drying of the wet granules at 60 for 15 min.Dry sieving of granules through 16 meshes.Adding starch and talcum powder to dry granules with blending uniformly.Compressing the granules into tablets.制软材制湿粒研磨混合干燥整粒压片混合制淀粉浆single-punch pressrotary tablet press2. Single-punch pressmanual driving whe

15、el hopper feed shoe cam gearing core components die (模圈) lower punch (下冲) upper punch (上冲) 3. Installing of single-punch pressInstalling of core componentsInstalling of the lower punch安装下冲： 旋松下冲固定螺钉，转动大皮带轮使下冲芯杆升到最高位置，将下冲插入下冲芯杆的孔中（注意使下冲杆的缺口斜面对准下冲紧固螺钉，并要插到底）最后旋紧下冲固定螺钉。Installing of the lower punch安装上冲

16、：旋松上冲紧固螺母，将上冲插入上冲芯杆的孔中，要插到底，旋紧上冲紧固螺母。Installing of the mould安装中模：旋松中模固定螺钉，将中模拿平放入中模台板的孔中，旋紧中模固定螺钉。缓缓转动大皮带轮，调整中模台板的位置，使上冲进入中模孔中，旋紧中模台板固定螺钉。(2) Adjustment of out-of-tablets 出片调整转动大皮带轮使下冲升到最高位置，观察下冲口面是否与中模平面相齐（或高或低都将影响出片），若不齐则旋松蝶形螺丝，松开齿轮压板转动上调节齿轮，使下冲口面与中模平面相齐，然后将压板按上，旋紧蝶形螺丝。用手转动大皮带轮，空车运转若正常，则可加料试压，进行下一

17、步调整。(3) Adjustment of tablet weight片重调节旋松蝶形螺丝，松开齿轮压板。转动下调节齿轮向左转使下冲芯杆上升，则充填深度减少（药片重量减轻）。调节好后将轮齿压板按上，旋紧蝶形螺丝。(4) Adjustment of tablet hardness硬度调节旋松连杆锁紧螺母、转动上冲芯杆，向左转使上冲芯杆向下移动，则压力加大，压出的药片硬度增加；反之，硬度降低。调节好后用扳手卡住上冲芯杆下部的六方，将连杆锁紧螺母锁紧。4. Tablet compression压片冲模的安装、调试完成后，即可启动电机试压，检查片重、硬度和表面光洁度等，质量如合格，即可投料批量生产。在

18、生产过程中仍须随时检查药片质量，及时调整。5. Quality control of tabletsAfter manufacturing tablets, a series of tests are carried out to assure that they meet the specifications of pharmacopoeia or industry standards. These tests are as listed on the right:WeightWeight variationDisintegrationHardnessFriabilityDissolutio

19、nDrug content uniformityThickness(1) Tablet weight and weight variationThe quantity of fill placed in the die cavity of a tablet press determines the weight of the resulting tablet.Weight variation: sample amount 20 tablets.Tablets should comply with the following requirements stated in the table be

20、low.Average weightWeight variation limitLess than 0.3 g 7.5%0.3 g or more 5%(2) Tablet hardnessIn general, tablets should be sufficiently hard to resist breaking during normal handling, packaging and shipping, and yet soft enough to disintegrate properly after swallowing. Hardness of the tablet is c

21、ontrolled by (or is affected by) the degree of the pressure applied during the compression stage. (2) Tablet hardnessSample amount 4 tablets.(3) Tablet disintegration testTablets must be tested to ensure disintegration. The CP, BP, USP and EP have official standards, including descriptions of the ap

22、paratus type dimensions and test conditions.(3) Tablet disintegration testSample amount 6 tablets.(4) Tablet friabilityThis test shows the strength of tablets against mechanical attrition. Method: allowing the tablets to roll and fall within the rotating apparatus (friabilator); determine the loss i

23、n weight; Requirement: weight loss 1%(4) Tablet friabilityExperimental Instructions1. Aspirin acid should be milled and forced through screen (80 mesh), then mix with excipients, usually we use the method that mass increased as others increased, screen and mix several times to insure uniformly mixed. 2. The dosage of adhesives should be aptitude to make the soft material be conglomeration in hand and when fingers press it slightly, it should disperse but does not turn into powders. 3. Aspirin is unstable in wet or heat environment, and when encountering with iron, it can hyd