摘要
Adefovir dipivoxil (9-(2-bis(pivaloyloxymethyl)phosphono methoxyethyl)adenine), ADV)是核苷酸反轉錄酶抑制劑(nucleoside reverse transcriptase inhibitor, NRTI) adefovir (9-(2-phosphonylmethoxyethyl)adenine, PMEA)的酯類前驅物，可用來治療慢性B型肝炎、人類免疫缺陷病毒(human immunodeficiency virus, HIV)與人類巨細胞病毒感染，及對lamivudine產生抗藥性的病患。 因ADV在含水的環境中非常不安定，易加速此藥物的降解反應（水解與偶聚作用）；為此，藉由添加賦形劑，將ADV設計成固體分散圓粒劑型，其優點如下，(1)其間隙與空氣接觸面小，不易氧化潮解，(2)賦形劑為非水物質，不易引起水解，可提高藥物的安定性。 本實驗以polyethylene glycol (PEG) 4000 與PEG 6000為塑化劑，carboxymethylcellulose sodium (CMC-Na) 為崩散劑與Tween 80為助溶劑，總共試製十種配方。利用示差掃描熱分析(different scanning calorimetry, DSC)檢測ADV與賦形劑，結果發現，ADV已經不再具有原本的晶格排列，而是均勻地分散於賦形劑中。另將所有配方與原廠錠劑進行溶離試驗比對，結果發現大部分配方溶離速率比原廠錠劑快。利用光學顯微鏡，圓度分析試驗中得知，所有配方之圓化程度均不錯。在含量差異試驗的結果發現，平均ADV在每克賦形劑中約含10 (mg)，從9.6 (mg)至10.2 (mg)，呈現相當不錯的均一度。最後，利用掃描式電子顯微鏡(scanning electron microscopy, SEM)來檢測物體之表面結構，結果發現，表面稍略粗糙、有孔洞。因此，從實驗結果顯示，利用此劑型可以找到理想的ADV配方。
並列摘要
Adefovir dipivoxil (9-(2-bis(pivaloyloxymethyl)phosphonomethoxyethyl) adenine), ADV) is an ester prodrug of the nucleoside reverse transcriptase inhibitor (NRTI) adefovir (9-(2-phosphonylmethoxyethyl)adenine, PMEA) and indicated for the treatment of chronic type B viral hepatitis, human immunodeficiency virus (HIV) infection and cytomegalovirus infection. The administration of oral ADV significantly reduces HIV ribonucleic acid (RNA) levels and also demonstrates activity against HIV strains resistant to lamivudine. ADV conspicuously accelerates degradation containing hydrolysis and dimerization under high humidity circumstances and therefore appears an unstable condition. For this reason, various excipients and preparations were utilized for modifying stabilization of ADV dosage form. Innovative ‘‘solid dispersion pills’’ (pills) devised to conquer above issues possess numerous advantages such as followings (1) It’s not effortless to result oxidation and deliquesce on account of small contact areas between pills and the air. (2) Pills apparently improve stabilization of drug and doesn’t readily produce hydrolysis owing to excipients are not aquiferous. Ten formulations containing polyethylene glycol (PEG) 4000 as base, PEG 6000 as base, carboxymethylcellulose sodium (CMC-Na) as disintegrants and Tween 80 as solubilizer were designed. Host-guest relationships were investigated in the solid state by different scanning calorimetry (DSC). Results of DSC spectra indicated that ADV didn’t maintain any longer its physicochemical characterization in excipients. It was demonstrated that lattice structures of ADV were exhaustively destroyed and ADV sufficiently dispersed in the base. Dissolution of whole formulations were performed in order to compare with in vitro release of Hepsera® tablets. Dissolution rates of most formulations were more rapid than those of Hepsera® tablets. Roundness employing optical microscopy and uniformity content of pills were surveyed and all formulations showed excellent roundness and uniformity, respectively. Finally, the scanning electron microscopy (SEM) was used to examine the detail shape of pills. Photos of morphology exhibited concave and coarse surface of pills. In accordance with experimental results, ideal formulations for ADV could be contrived by means of dosage form of pills.