這項研究的目的是以 Didanosine 和 Doxycycline Hyclate 當作模式藥物，評估擠壓搓圓製備後的腸溶性膜衣包覆圓粒，於不同顆粒大小，包覆不同腸溶性聚合物之厚度與腸溶性聚合物之比例，在不同 pH 值下對溶離的影響。
Didanosine (DDI) 是有效的治療患者體內的 HIV 病毒而抑制 HIV 複製之藥品。DDI 屬於不耐酸性之藥物，所以必須以腸溶性聚合物包覆，使藥物在胃中可被保護至腸再釋放。Doxycycline Hyclate (DXH) 是屬於抗生素種類的四環黴素。DHX 屬於胃刺激性藥物，須以腸溶性膜衣包覆，使藥物通過胃時不刺激胃，而到達腸道再使藥物釋放。
在製備藥物過程中，未包覆膜衣的圓粒，是使用擠壓搓圓的技術所製備而成。造粒時乃使用水混合，模式藥物和水溶性高分子材料，黏合劑，及崩散劑，形成濕團。濕團經由擠壓搓圓後，再烘乾形成未包覆膜衣的圓粒。
模式藥物利用腸溶性聚合物包覆，於各種製程及處方的變異，包括圓粒大小、腸溶性聚合物所包覆圓粒之厚度及腸溶性聚合物的比例，發現在各種不同溶離的溶液會影響藥物釋放動力學。本研究中得到圓粒尺寸大的比小尺寸圓粒溶離速率較慢，未包覆聚合物的圓粒溶離速率，較有包覆聚合物的圓粒溶離速度快，包覆較厚聚合物的圓粒溶離速率，比包覆較薄聚合物的圓粒溶離速率慢，以及包覆腸溶性聚合物 HPMCP 比例較高者，其溶離速率較慢。
由本研究了解，藉由調整適合的製劑變因可控制藥物的釋放，使其可避免藥物在胃部之裂解及刺激，在到達適合的小腸吸收位置後，再進行藥物的釋放。 The purpose of this study is to prepare and evaluate enteric coated pellets after extrusion/spheronization. The various formulation variables studied, including pellet size, amount of enteric polymer (coating thickness) and soluble polymer/enteric polymer ratio were found to affect drug release kinetics in various dissolution media. Both Didanosine and Doxycycline Hyclate were used as model drugs.
Didanosine (DDI) is known to be effective in the treatment of patients with HIV virus by inhibiting HIV replication. DDI is an acid labile drug, therefore it has to be coated with enteric polymer in order to protect the drug in the stomach and to be released in intestine. Doxycycline Hyclate belongs to Tetracyclines antibiotics. DXH is irritant to stomach, thus to release the drug in intestine via enteric coating is necessary to reduce adverse effects.
In the process of preparing drug containing pellets, the uncoated pellets are formed using extrusion/spheronization methodology. The granulation solvent mixed with the model drug and water soluble materals, a binder, and a disintegrant, to form a wet mass. The wet mass was extruded/spheronized and then dried to form uncoated pellets.
Enteric coating of model drug are available after polymer coating process. Various formulation variables, including pellet size, amount of enteric polymer (coating thickness) and soluble polymer/enteric polymer ratio were found to affect drug release kinetics. On the pellet size, formulations with larger size have slower release rate. Uncoated pellets have faster drug release, where as pellets with thicker polymer coating results in slower drug release. Finally, pellets with higher HPMCP/HPMC ratio of polymer coating results in slower drug release.
According to the results, via adjusting appropriate formulation variables, delayed release of model drugs is achievable in order to avoid drug degradation and drug irritation in stomach.
