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研究生:陳淑娟
研究生(外文):Shu-Chuan Chen
論文名稱:Chlorzoxazone口腔快速崩散錠之處方研究
論文名稱(外文):A Study on Formulation of Orally Rapidly Disintegrating Chlorzoxazone Tablets
指導教授:詹道明詹道明引用關係
指導教授(外文):Thau-Ming Cham
學位類別:碩士
校院名稱:高雄醫學大學
系所名稱:藥學研究所碩士班
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2007
畢業學年度:95
語文別:中文
論文頁數:91
中文關鍵詞:chlorzoxazone口腔快速崩散錠試驗設計法
外文關鍵詞:chlorzoxazoneorally rapidly disintegrating tabletsexperimental design
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Chlorzoxazone是中樞作用的肌肉鬆弛劑,它可用來治療腰痛、肩酸、神經痛,降低因運動後之肌肉酸痛、痙攣及強直。口腔快速崩散錠是一種在口腔內就可快速崩散完成的固體劑型,可以減少錠劑吞嚥的困難。將錠劑放入口腔中,唾液可以快速地滲透到錠劑孔洞裡,而使錠劑崩解。
本實驗利用複因子試驗設計法來找出最適合chlorzoxazone口腔快速崩散錠的處方。本實驗採用23試驗設計法以口腔快速崩散錠的崩散時間為依據,接著使用ANOVA來分析變因。探討其物性包括崩散時間、硬度、脆度、含量均一度以及體外溶離等實驗。再利用示差掃描熱分析儀(DSC)及傅立葉轉換式紅外線光譜儀(FT-IR)來探討chlorzoxazone與賦型劑之間的交互關係。
試驗設計法證明崩散劑濃度及打錠壓力對口腔快速崩散錠崩散時間有顯著影響。DSC及FT-IR分析結果指出chlorzoxazone-HP?毧D成功被製備,chlorzoxazone口腔溶解錠之賦形劑間沒有相互作用的影響,由最佳化的處方可得到最短的崩散時間為8.3秒。
Chlorzoxazone is a muscle relaxant of central nervous system. It is used in the treatment of lumbago, shoulder ache, nerve ache, reduction the symptom of muscle ache, muscle convulsion and muscle tetanus after sports. Orally rapidly disintegrating tablets are solid dosage forms that disintegrate in the oral cavity leaving an easy-to-swallow residue.
A statistical factorial experimental design was used to optimize the formulation of orally rapidly disintegrating chlorzoxazone tablets. A 23 experimental design was employed to evaluate the disintegration of the orally rapidly disintegrating tablets; subsequent data was compared using analysis of variance (ANOVA). The characterization of the orally rapidly disintegrating tablets were studied, such as disintegration time, hardness, friability, uniformity content of the tablets, and in-vitro release test of the orally rapidly disintegrating chlorzoxazone tablets. Host-guest interactions were studied in the solid state by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR).
The experimental design study illustrated that the concentration of disintegrants and compression force had significant effect on the disintegration time. The results of DSC and FTIR spectra indicated that chlorzoxazone-HP?毧D was prepared successfully and no interaction between chlorzoxazone and excipients. An optimum formulation showed a shortest disintegrating time of 8.3 s.
目錄

表次目錄................................................................................................. III
圖次目錄................................................................................................. IV
中文摘要................................................................................................ VII
英文摘要.............................................................................................. VIII

本文

第一章 緒論............................................................................................. 1
一、下背痛基本概論............................................................................. 1
二、藥物介紹-chlorzoxazone基本概述.............................................. 13
三、環糊精之介紹............................................................................... 16
四、口腔快速崩散錠簡介................................................................... 25
五、實驗設計法................................................................................... 28
第二章 實驗目的................................................................................... 33
第三章 實驗材料與儀器設備............................................................... 34
一、實驗材料....................................................................................... 34
二、實驗儀器設備............................................................................... 35
第四章 實驗方法................................................................................... 36
一、高壓液相層析儀(HPLC)分析chlorzoxazone方法..................... 36
二、Chlorzoxazone複合物之製備..................................................... 37
三、Chlorzoxazone- HP?毧D複合物之相溶解度試驗.......................38
四、篩選實驗設計法之因子.............................................................. 39
五、複因子實驗設計法探討chlorzoxazone口腔快速崩散錠之組成........................................................................................................ 40
六、Chlorzoxazone口腔快速崩散錠之製備..................................... 41
七、口腔快速崩散錠之物理檢測...................................................... 42
八、含量均一度試驗.......................................................................... 43
九、體外溶離試驗.............................................................................. 44
十、探討口腔快速崩散錠處方之交互作用...................................... 45
十一、安定性試驗.............................................................................. 46
第五章 結果與討論............................................................................... 47
一、Chlorzoxazone之分析方法......................................................... 47
二、Chlorzoxazone- HP?毧D複合物之相溶解度試驗...................... 49
三、篩選實驗設計法之因子.............................................................. 51
四、複因子實驗設計法探討Chlorzoxazone實驗數據之統計結果分析........................................................................................................ 52
五、口腔快速崩散錠之物理檢測..................................................... 64
六、含量均一度試驗......................................................................... 65
七、Chlorzoxazone口腔快速崩散錠與原廠之溶離試驗................. 66
八、Chlorzoxazone複合物檢測及口腔快速崩散錠處方之交互作用....................................................................................................... 67
第六章 結論........................................................................................... 84
第七章 參考文獻................................................................................... 85

表次目錄

表1:非固醇類抗發炎藥物(Non-Steroidal Anti-Inflammatory Drugs)....................................................................................................... 8
表2:骨骼肌鬆弛劑藥物........................................................................... 9
表3:環糊精之基本物性......................................................................... 17
表4:設計矩陣(design matrix)............................................................. 31
表5:處方A及B...................................................................................... 39
表6:處方C及D...................................................................................... 39
表7:處方E及F....................................................................................... 40
表8:23複因子試驗設法之試驗因子..................................................... 40
表9:23複因子試驗設法之處理組合表................................................. 41
表10:23複因子試驗設法之8種處方實際重量.................................... 41
表11:Chlorzoxazone定量方法之同日間與異日間分析結果.............. 48
表12:處方A和B的平均崩散時間....................................................... 51
表13:處方C和D的平均崩散時間....................................................... 51
表14:處方E和F的平均崩散時間........................................................ 52
表15:23複因子試驗設法之ANOVA分析表........................................ 53
表16:23複因子試驗設法之8種處方殘差值........................................ 53
表17:處方6之硬度試驗結果................................................................ 64
表18:處方6之脆度試驗結果................................................................ 64
表19:處方6之崩散試驗結果................................................................ 65
表20:處方6之單位含量均一度試驗結果............................................ 65

圖次目錄

圖1:Chlorzoxazone結構........................................................................ 13
圖2:多突觸的抑制反射......................................................................... 14
圖3:Chlorzoxazone和代謝物6-hydroxychlorzoxazone....................... 14
圖4:環糊精之結構................................................................................. 17
圖5:形成複合物的作用機轉................................................................. 20
圖6:23複因子實驗設計八個處理組合所形成立方體的幾何圖形............................................................................................................. 30
圖7:Chlorzoxazone之高效液相層析圖................................................ 47
圖8:Chlorzoxazone檢量線圖................................................................ 48
圖9:相溶解度典型等溫線圖................................................................. 50
圖10:Chlorzoxazone與不同莫耳濃度HP-?毧D溶液之相溶解圖....... 50
圖11:A因子與B因子之交互效應的標準誤差圖................................ 56
圖12:A因子與C因子之交互效應的標準誤差圖................................ 56
圖13:B因子與C因子之交互效應的標準誤差圖................................ 57
圖14:殘差質與正常%機率之檢查....................................................... 57
圖15:崩散時間之殘差值與預測值檢查............................................... 58
圖16:崩散時間之預測值與實際值檢查............................................... 58
圖17:崩散時間之殘差與實驗順序檢查............................................... 59
圖18:殘差值與黏合劑濃度之檢查....................................................... 59
圖19:殘差值與崩散劑濃度之檢查....................................................... 60
圖20:殘差值與打錠壓力之檢查........................................................... 60
圖21:A因子之主效應圖....................................................................... 61
圖22:B因子之主效應圖....................................................................... 61
圖23:C因子之主效應圖....................................................................... 62
圖24:A因子與B因子之間的交感效應圖............................................ 62
圖25:A因子與C因子之間的交感效應圖............................................ 63
圖26:B因子與C因子之間的交感效應圖............................................ 63
圖27:Chlorzoxazone口腔快速崩散錠與原廠藥溶離釋出圖.............. 66
圖28:Chlorzoxazone之DSC圖............................................................. 69
圖29:?毧D之DSC圖.............................................................................. 69
圖30:HP?毧D之DSC圖......................................................................... 70
圖31:Chlorzoxazone與?毧D物理混合之DSC圖................................. 70
圖32:Chlorzoxazone與HP?毧D物理混合之DSC圖........................... 71
圖33:Chlorzoxazone-?毧D複合物之DSC圖........................................ 71
圖34:Chlorzoxazone-HP?毧D複合物之DSC圖................................... 72
圖35:Crospovidone之DSC圖............................................................... 72
圖36:Mannitol之DSC圖....................................................................... 73
圖37:Avcel PH 102之DSC圖............................................................... 73
圖38:Chlorzoxazone口腔快速崩散錠之DSC圖................................. 74
圖39:Chlorzoxazone之FT-IR圖........................................................... 77
圖40:?毧D之FT-IR圖............................................................................ 77
圖41:HP?毧D之FT-IR圖....................................................................... 78
圖42:Chlorzoxazone-?毧D物理混合之FT-IR圖.................................. 78
圖43:Chlorzoxazone-HP?毧D物理混合之FT-IR圖............................. 79
圖44:Chlorzoxazone-?毧D複合物之FT-IR圖...................................... 79
圖45:Chlorzoxazone-HP?毧D複合物之FT-IR圖................................. 80
圖46:Crospovidone之FT-IR圖............................................................. 80
圖47:Mannitol之FT-IR圖..................................................................... 81
圖48:Avicel PH 102之FT-IR圖............................................................ 81
圖49:Chlorzoxazone口腔快速崩散錠之FT-IR圖............................... 82
圖50:貯存在25 °C/ 60% R.H.及40 °C/ 75% R.H.之條件下chlorzoxazone-HP?毧D口腔快速崩散錠衰變圖................................... 83
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