[生物医药论文精品]复方单硝酸异山梨酯缓释片薄膜包衣工艺研究

1复方单硝酸异山梨酯缓释片薄膜包衣工艺研究摘要目的探讨了复方单硝酸异山梨酯缓释片的薄膜包衣工艺。方法采用正交试验确定薄膜包衣的工艺参数，选择最佳工艺条件。结果确定了薄膜包衣的最佳工艺条件包衣的羟丙甲纤维素量为20，喷速009011KGMIN1，片芯水分为47，片芯硬度为1014KGMM21。最主要的影响因素为包衣液浓度和片芯硬度。结论薄膜衣片在增重、外观、吸湿性、溶出度和释放度方面非常良好，工艺稳定可行。关键词复方单硝酸异山梨酯缓释片；薄膜包衣；正交试验；片芯FILMCOATINGOFCOMPOUNDISOSORBIDEMONONITRATESUSTAINEDRELEASETABLETSABSTRACTOBJECTIVETOSTUDYTHEOPTIMUMCONDITIONSOFCOMPOUNDISOSORBIDEMONONITRATESUSTAINEDRELEASETABLETSMETHODSTHEOPTIMUMFACTORSOFCOMPOUNDISOSORBIDEMONONITRATESUSTAINEDRELEASETABLETSWEREESTABLISHEDUSINGTHEORTHOGONALDESIGNMETHODRESULTSTHEOPTIMIZEDPARAMETERSOFFILMCOATINGAREASFOLLOWSTHECONCENTRATIONOFTHEHPMCIS20，THESPRYFLOWIS009011KGMIN1,WATERCONTENTTHETABLETCOREIS47ANDHARDNESSOFTHATIS1014KGMM21ANDTHEKEYINFLUENCINGFACTORSARECONCENTRATIONOFTHECOATINGFLUIDANDHARDNESSOFTHETABLETCORECONCLUSIONTHEINCREASEDWEIGHT,APPEARANCE,HYGROSCOPICITY,DISSOLUTIONANDDELIVERYOFTHEFILMCOATINGTABLETSAREGOODTHECRAFTISSTABLEANDPRACTICABLEKEYWORDSCOMPOUNDISOSORBIDEMONONITRATESUSTAINEDRELEASETABLETS；FILMCOATING；ORTHOGONALDESIGNMETHOD；TABLETCORES复方单硝酸异山梨酯缓释片由英国纳普公司（NAPP）首先研发成功，并于1999年上市。临床用于治疗慢性心绞痛和充血性心力衰竭等G11163，G4600G1866G17878用于G1908G14045G7438G14033G993G1852的心绞痛。G16825G2058G2070G1025单硝酸异山梨酯为缓释成分，G19475司G2317G7531为速释成分，缓释G18108分G994速释G18108分分为G1016G4630G2399G2058在G980G17227，G2058成复方缓释G2058G2070，G7094方G1427G2460G18003G1825了G13796G2475性和G11161G5785G2465G17351，G1209G2462单用G9443G7393G10628G169491。G7424研G12362G7100在G4570G17839G2487G1147G2709国G1147G2282，G2031G17908良好的G12050G1262G13475G8994G6940G11422。由于薄膜包衣G1867G7389G5468G3822G1260G98691片G2070增重G4581，G14033G14422G13434G3835量G17753G7021；2G6564G20652了G10995G1147G6940G10587，可G3835G3835G13565G11713G10995G1147工G5219G7114G19400，G1955G4581G14033G13803，G6564G20652G16786G3803G2045用G10587，G7186G14891G19489G1314G10995G1147成G7424；G22G6925G2904G10995G1147G10627G3671，G19489G1314G2183G2172G5390度；G23薄膜衣G7460G7021G6251湿性G17751好，G1147G2709G17148量稳定；G24采用了G20652分G4388G7460G7021，G2474G9052了G15083G12970，G7368G7389G2045于G13781年G1166和G12970G4627G11161G5751G13785的G1363用，确G1457G146592G10301的疗G6940和G4445G1852性。为了G6564G20652G1147G2709G17148量，G6117G1216G4557复方单硝酸异山梨酯缓释片G17839行了薄膜包衣工艺研G12362。选用羟丙甲纤维素G1328为成膜G7460G7021；由于G19475司G2317G7531G7143水G16311G13792G10995成水G7484酸，因G8504选用80乙醇G1328为包衣液溶G2070。另外影响包衣合格G10587的因素G7389包衣液浓度、流量、片芯水分、片芯硬度，采用L9（G224）正交表确定薄膜包衣的最佳工艺参数，从G13792G6564G20652了G1147G2709的包衣G17148量。1设备和材料BGB1G240CG20652G6940包衣G7438（温州G2058G14659G16786G3803厂）；GZP240C旋转式G20652速G2399片G7438（北京国G14659龙立科技G7389限公司）；ZRS8智G14033溶出度试验仪（天津G3835学无线电厂）；AGILENT1100G20652G6940液相色谱仪（美国G4445捷伦公司）；UV2401PC紫外可见分光光度计（日G7424岛津G2058G1328所）；羟丙甲纤维素（G4445徽山河G14659用G17753G7021G7389限公司）；二氧G2282钛（超细，江苏鹏鹞G14659业G7389限公司）；聚山梨酯80、蓖麻油（湖南尔康G2058G14659G7389限公司）；丙二醇、G14659用滑石粉、乙醇等。2实验方法和结果21包衣液的配G2058先用80乙醇G2058G3803出羟丙甲纤维素浆，然后内加G14659用滑石粉、二氧G2282钛、聚山梨酯80、蓖麻油、丙二醇，充分搅拌均匀后，过胶体磨并用120目筛过滤，G3803用。22正交试验G16786计片芯的硬度G4557于包衣合格G10587影响甚G3835，硬度过G1314，包衣过程发G10995崩片、碎片G3822；硬度过G20652，影响片G4388的溶出。包衣液的配G2058方面也G5468重要，太稠容G7143堵塞喷枪；太稀则水分过G3822，则干燥慢，包衣G7114G19400过长，同G7114也影响G19475司G2317G7531的稳定性。包衣液流量过G3835G1262G1363片芯来G993G2462干燥，导致粘片、粘锅；流量太小，同样G1262延长包衣G7114G19400，G4557片芯磨损G17751G3835。G7424实验选择包衣液浓度、流量、片芯水分和片芯硬度G1328为考察因素，选用L9（G224）正交表G17839行试验，G4557薄膜包衣合格G10587G17839行考察。因素水平见表1，结果见表2。表1因素水平表TAB1LEVELOFFACTORSLEVELFACTORSACONTENT/BFLOWRATE/KGMIN1CMOISTUREOFTABLETCORES/DHARDNESSOFTABLETCORES/KGMM2111G2401G22016G22G24101G2322001201G23G237710G222G24009011810G237表2正交试验表G2462结果TAB2ORTHOGONALDESIGNTABLEANDRESULTS3ABCDQUALIFICATIONRATEOFFILMCOATING/1111192821222882G221G22G22G2286G24G23212G2296G23G2422G22199662G22129827G221G2228G23G238G2221G228079G22G2221962267G2427G22627172886G26629G232268G2428082708G267261G222809270G2426G226892912906962G26698189G249G22690G22G2678719G226902879G5311G231G22G238G22G4557正交试验的结果G17839行G11464观分G7524，薄膜包衣的最佳工艺条件为A2B3C2D1，G2375包衣液浓度20，流量009011KGMIN1，片芯水分为G237，片芯硬度为101G23KGMM21。从G12227G5058G17836可G1209G11487出，包衣液浓度G4557包衣合格G10587影响最G3835，片芯硬度G8437G1055，G13792包衣液流量和片芯水分影响G17751小。2G22G4557薄膜包衣片的G17148量考察2G221包衣后的增重先G247420片片芯，G12946G4506G12228定G5647重量，G8726G5483平均片重，G1889分G2047G12946G1222820片薄膜包衣片，也G8726G5483平均片重，计G12651出包衣后的片重，结果见表G22。表G22包衣增重G5058异TAB3THEDIFFERENCESOFINCREASEDWEIGHTAFTERCOATINGTABLETCOREWEIGHT/GWEIGHTAFTERCOATING/GINCREASEDWEIGHT/G230G23G239G230G23727G242G240G23G22860G23G248G23G23G2460G23G23680G23677G23790G23G240G230G23721G2382G222溶出度和释放度4G2474包衣合格G10587G17751G20652的G23、G24、6、9G2507试验的片G4388G17839行溶出度和释放度G7828G7609，方G8873G3926G991。溶出度（G19475司G2317G7531）G2474G7424G2709，G10043溶出度G8991定G8873（G1025国G14659G1868200G24年G10268二G18108G19480G5417G59CG12544G980G8873），G1209G11979酸G11428缓G1926液（G83G4368）G2400ML为溶G2070，转速为G8611分G19059G240转，G1393G8873G6817G1328，G13475G220分G19059G7114，G2474溶液10G80G79滤过；G2474G13505滤液G1328为G1391试G2709溶液，G10043紫外可见分光光度G8873（G1025国G14659G1868200G24年G10268二G18108G19480G5417G44G57G36），在26G24NM的G8886长G3800G8991定吸G6922度。另G2474G19475司G2317G7531G4557G10043G2709G17878量，G12946G4506G12228定，用G11979酸G11428缓G1926液（G51G4368）溶G16311并稀释G2058成G86111MLG1025G13434G255901G24MG的溶液，G1328为G4557G10043G2709溶液，同G8873G8991定。G6365二G13785吸G6922度的G8616G1552计G12651出G8611片G19475司G2317G7531的溶出量。限度为G7643G12046量的80，G5224G12538合G16280定。释放度（单硝酸异山梨酯）G2474G7424G2709，G10043释放度G8991定G8873（G1025国G14659G1868200G24年G10268二G18108G19480G5417G59G39G12544G980G8873）G8991定，采用溶出度G8991定G8873G12544G980G8873的G16025G13634，G1209G11979酸G11428缓G1926液（G83G4368）G2400G80G79为溶G2070，转速为G8611分G19059G240转，G1393G8873G6817G1328。在1小G7114、G23小G7114和8小G7114G7114分G2047G2474溶液G24G80G79滤过，并G2375G7114在G6817G1328容G3132G1025G15929充上G17860溶G2070G24G80G79。G2474G13505滤液，G10043单硝酸异山梨酯G2559量G8991定G8873G62液相色谱G8873用G2325G1855G9931G3534G11801G9931G19202合G11801胶为G3647充G2070，G1209乙G14108水（20G29780）为流G2172相，G7828G8991G8886长为210NM。G10714G16782G7507数G6365单硝酸异山梨酯G4804计G12651G5224G993G1314于1000，单硝酸异山梨酯G4804G994G19475司G2317G7531G4804的分G12175度G5224G12538合要G8726G64G8991定，G12946G4506量G2474G13505滤液20G173G79G8892G1849液相色谱仪G16772G5417色谱G3282；另G2474G13475G1128氧G2282二G11979G1955G2399干燥G14279G5670重的单硝酸异山梨酯G4557G10043G2709G17878量，G12946G4506G12228定，加流G2172相溶G16311并稀释G2058成G86111G80G79G1025G13434G2559012MG的溶液，同G8873G8991定。G6365外G7643G8873G1209G4804面G12227分G2047计G12651出G8611片在G993同G7114G19400的单硝酸异山梨酯溶出量。G7424G2709G8611片在1小G7114、G23小G7114和8小G7114的单硝酸异山梨酯溶出量G5224分G2047为G7643G12046量的10G794G230，G230G7947G24和70G1209上，均G5224G12538合G16280定。结果见表G23。表G23溶出度和释放度试验结果TAB4TESTINGRESULTSOFDISSOLUTIONANDRELEASEDISSOLUTION（ASPIRIN）RELEASE（ISOSORBIDEMONONITRATE）G239691G752G23G23G23HG242G248H8G236G2492G231G75207G23HG23828G7580669G2361G75227G23G75G240G248G758G22998961G75218G23G75G23928G7580852G22G22吸湿性试验在G6962G2487G3533G1871G11411G1025，G13634RH7G24的G10627G3671G1025，G8611天G12228重，计G12651吸湿G10587并观察外观G5785G1929，结果见表G24。表G24薄膜衣片吸湿性试验结果TAB5HYGROSCOPICITYDETERMINATIONRESULTSOFTHEFILMCOATINGTABLETSAPPEARANCEMOISTUREABSORPTIONRATE/G23G4448G6984光G8917，色G8913均匀0G248G24G4448G6984光G8917，色G8913均匀0626G4448G6984光G8917，色G8913均匀06G229G4448G6984光G8917，色G8913均匀0G246G7828验结果表G7138薄膜衣片外观G3534G7424G8821G7389G2476G2282，吸湿G10587也G8616G17751G1314，G16840G7138薄膜包衣片的G6251湿性G17751好。3小结与讨论G17902过正交试验，确定了薄膜包衣的最佳工艺条件为包衣液浓度20，流量009011KGMIN1，片芯水分为G237，片芯硬度为101G23KGMM21。G1866G1025包衣液浓度和片芯硬度G4557包衣合格G10587影响最G3835。由于G7424G2709为G2464G4630片，G4557片芯的硬度要G8726G17751G20652，在10KGMM21G1209上G17751为合G17878，G1306硬度太G3835，G1262影响片G4388的溶出度和释放度，同G7114也G1262G13485G2399片的G10995G1147G5114来G3268G19602，因G8504选择片芯硬度为101G23KGMM21G17751为G17878G4464。G5332G3999包衣研G12362G7114G6117G1216选择G2357G1060康水性包衣G7460G7021，包衣后结果出G10628G19475司G2317G7531G18108分G14204G13972G2476G3835，因G8504G6925用羟丙甲纤维素成膜G7460G7021，80乙醇为溶G2070。包衣G6817G1328G7114，为了G19462G8502喷液G1025的水分G9195G1849片芯，G2563喷前必须在锅G1025把片G4388预热G142793545，喷雾G5332G3999G7114量可G1209稍G3835些，G1363片芯G1852G18108湿润，刚好形成G980G4630膜。吹热风干燥后G19489G1314喷雾速度和热风干燥温度，继G13505喷雾，喷速可掌握在片面手感G7389湿润G2460G993粘手为G4464，因为片芯表面太湿，膜G4630G7143G17227泡，且G7143出G10628皱