片劑的制備 工業(yè)藥劑

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 混合壓片填充劑黏合劑崩解劑API

11、輔料粉碎和過(guò)篩制軟材干燥整?；旌现茲窳?rùn)滑劑崩解劑濕法制粒壓片工藝流程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.制軟材制濕粒研磨混合干燥整粒壓片混合制淀粉漿single-punch pressrotary tablet press2. Single-punch pressmanual driving whe

15、el hopper feed shoe cam gearing core components die (模圈) lower punch (下沖) upper punch (上沖) 3. Installing of single-punch pressInstalling of core componentsInstalling of the lower punch安裝下沖： 旋松下沖固定螺釘，轉(zhuǎn)動(dòng)大皮帶輪使下沖芯桿升到最高位置，將下沖插入下沖芯桿的孔中（注意使下沖桿的缺口斜面對(duì)準(zhǔn)下沖緊固螺釘，并要插到底）最后旋緊下沖固定螺釘。Installing of the lower punch安裝上沖

16、：旋松上沖緊固螺母，將上沖插入上沖芯桿的孔中，要插到底，旋緊上沖緊固螺母。Installing of the mould安裝中模：旋松中模固定螺釘，將中模拿平放入中模臺(tái)板的孔中，旋緊中模固定螺釘。緩緩轉(zhuǎn)動(dòng)大皮帶輪，調(diào)整中模臺(tái)板的位置，使上沖進(jìn)入中?？字?，旋緊中模臺(tái)板固定螺釘。(2) Adjustment of out-of-tablets 出片調(diào)整轉(zhuǎn)動(dòng)大皮帶輪使下沖升到最高位置，觀察下沖口面是否與中模平面相齊（或高或低都將影響出片），若不齊則旋松蝶形螺絲，松開(kāi)齒輪壓板轉(zhuǎn)動(dòng)上調(diào)節(jié)齒輪，使下沖口面與中模平面相齊，然后將壓板按上，旋緊蝶形螺絲。用手轉(zhuǎn)動(dòng)大皮帶輪，空車(chē)運(yùn)轉(zhuǎn)若正常，則可加料試壓，進(jìn)行下一

17、步調(diào)整。(3) Adjustment of tablet weight片重調(diào)節(jié)旋松蝶形螺絲，松開(kāi)齒輪壓板。轉(zhuǎn)動(dòng)下調(diào)節(jié)齒輪向左轉(zhuǎn)使下沖芯桿上升，則充填深度減少（藥片重量減輕）。調(diào)節(jié)好后將輪齒壓板按上，旋緊蝶形螺絲。(4) Adjustment of tablet hardness硬度調(diào)節(jié)旋松連桿鎖緊螺母、轉(zhuǎn)動(dòng)上沖芯桿，向左轉(zhuǎn)使上沖芯桿向下移動(dòng)，則壓力加大，壓出的藥片硬度增加；反之，硬度降低。調(diào)節(jié)好后用扳手卡住上沖芯桿下部的六方，將連桿鎖緊螺母鎖緊。4. Tablet compression壓片沖模的安裝、調(diào)試完成后，即可啟動(dòng)電機(jī)試壓，檢查片重、硬度和表面光潔度等，質(zhì)量如合格，即可投料批量生產(chǎn)。在

18、生產(chǎn)過(guò)程中仍須隨時(shí)檢查藥片質(zhì)量，及時(shí)調(diào)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