- 學位論文
探討口溶崩散錠之Tamsulosin Hydrochloride 處方研究
Formulation design of tamsulosin hydrochloride orally disintegrating sustained-release tablets
摘要
口溶崩散錠 (ODTs) 目前受到相當大的重視，因其具有增加病患的順服性，可逐漸取代錠劑與膠囊，尤其在老年人與嬰幼兒族群的用藥安全上。現今口溶崩散錠的製備常利用具有功能性聚合物調控藥物釋放速度。本研究選用的模式藥物為tamsulsoin hydrochloride (TSH)，其為高選擇性腎上腺阻斷劑可有效治療下泌尿道排尿障礙症狀所產生良性前列腺肥大症。 本研究擬利用直接壓錠法建立簡便的口溶崩散錠製造方法，評估包覆藥物之高分子(乙基纖維素 (EC) and Eudragit® L100 (ED))、藥物溶媒和造粒液於口溶崩散錠的處方中，影響藥物在pH 6.8和pH 1.2置換到pH 7.2兩種溶離液中的釋放機制。實驗結果為48組處方在前面2小時為酸性環境下皆無藥物釋出，顯示包覆藥物之高分子材料皆可完整包覆藥物，使得藥物可順利到達腸道並釋放。體外溶離試驗結果亦顯示口溶崩散錠的藥物釋放機制與包覆藥物之膜衣材料有直接的相關性，在ED的重量比例比較高 (處方 ECED12GCD1W) 時，其在pH 6.8和pH 1.2 置換到pH 7.2溶離液的藥物釋放量分別為85.94 % 和88.94 %，然而若增加EC的重量比例(Formulation ECED21GC3G) 則會減少藥物釋放量，其在上述兩種溶離液的藥物釋放量分別為49.93 % 和 78.91 %，此種現象可能是乙基纖維素為水不溶的材質包覆藥物，所以會阻礙藥物的釋放。
關鍵字
口溶崩散錠並列摘要
Orally disintegrating tablets (ODTs) have gained considerable attention as a preferred alternative to conventional tablets and capsules due to better patient compliance, especially the geriatrics and pediatrics. While new generation of ODTs with specialized functional polymers can lead to ODTs with sustained-modified profiles. Tamsulosin hydrochloride (TSH), a highly selective α1a -adrenoreceptor antagonist that has been used for the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia, was employed as a model drug. The objective of this study was to establish a simple and flexible method of preparing ODTs using direct compression and evaluate the influence of coating polymers (ethylcellulose (EC) and Eudragit® L100 (ED)), drug solvent, and the granulating liquids-based formulations on the dissolution of model drugs in pH 6.8 medium and the change of medium pH from 1.2 to 7.2. Results showed all forty-eight formulations showed no drug release in the first 2 h in the gastric environment and the coating polymers used can protect ODTs from the acidic environment of the stomach and allow drug delivery to the small or large intestine. From the dissolution data obtained, it was also found that drug released from ODTs was directly related to the ratio of coating polymers applied. At a higher ratio of ED (Formulation ECED12GCD1W), the percent drug release at pH 6.8 and the change of medium pH from 1.2 to 7.2 were 85.94% and 88.94%, respectively. However, increasing the coating ratio of EC (Formulation ECED21GC3G) reduced the drug release at above two mediums to 49.93% and 78.91%, respectively. This phenomenon was probably associated with water-insoluble ethylcellulose to retard drug release.