Jellies for oral administration are dosage forms that contain water, as stipulated in the Japanese Pharmacopeia, and heat is generally applied to the jellies during the manufacturing process. Therefore, it is difficult to formulate drugs that may be affected adversely by water and/or heat. To solve this problem, we tried to develop a powder form of gel as a novel dosage form (dry jelly: jelly medicine extemporaneously prepared) that is converted to jelly after addition of water at the time of administration. For this purpose, a basic gel formulation consisting of pectin, glucono-δ-lactone, dibasic calcium phosphate hydrate, and sucrose was investigated to evaluate the critical factors affecting gelation phenomena. The gel form was developed by adjusting the amount of each component of the formulation and of water added. Gelation occurred even with hard water containing metal ions (hardness of approximately 304 mg/L), and no changes in gel hardness occurred. The desired gel hardness could be controlled by adjusting the amount of water. The gel hardness changed over time after the addition of water, but this change did not affect the dissolution behavior of drugs formulated in the dry jelly.

Oral gel formulations are known as easy to administer drug products for patients who have problems taking drugs including those with conditions such as dysphagia. In addition, there are numerous commercially available oral gel products, most of which are immediate-release formulation that release their pharmaceutical ingredient content by diffusion. This study is focused on developing oral gel formulations that reduce the dosing frequency and dosage compared to the conventional types. This is with the aim of facilitating the use of gel formulations for producing pharmaceutical agents with different dose regimens, thereby enhancing patient convenience. Here, we used naturally derived high-molecular-weight agar (Ag), xanthan gum (Xa), and locust bean gum (Lo) as gel bases to prepare a variety of gel membranes, and evaluated the diffusion coefficient of the model substances. The result revealed that the Ag content in the Xa-Lo combination gel concentrationdependently increased the diffusion coefficient. Moreover, these findings were applied in an attempt to mask the taste of intensely bitter levofloxacin. The results indicated that the Xa-Lo combination gel exhibited a significantly superior masking effect to that of the Ag gel. This study demonstrates the feasibility of using oral gel formulations to modulate the controlled-release functionality of pharmaceutical agents.Key words oral gel formulation; diffusion control; time lag method; naturally derived high-molecular-weight gel; dissolution profileIn recent years, proactive development of formulations that facilitate patient convenience in taking medicines has been encouraged to improve drug compliance and adherence. Examples of such efforts include orally disintegrating tablets, 1,2) film drug products, 3,4) and oral gel formulations. 5,6) The increasing trend of proactive research and development into these formulations may have been partly encouraged by a rapidly growing aging population worldwide. In particular, Japan is currently experiencing a situation where our population appears to enter into the phase of an aged society ahead of the rest of the world. This circumstance makes addressing the challenges for the prevention of diseases such as pneumonia aspiration associated with compromised swallowing functions in aged people a priority.Current research on oral gel products has focused on easeof-dosing that can be achieved by the proper flowability and easy chewability offered by gel formulations. Furthermore, these formulations can clinically enhance drug compliance in the elderly and patients with dysphagia and, therefore, they were primarily expected to be used in hospital dispensaries. However, advances in manufacturing machinery and technologies in recent years have gradually encouraged active research into gel formulations with a post-marketing projection. The beneficial effects of some oral gel formulation jellies have been demonstrated including Caloryl ® that contains lactulose as a hyperammonemia treatment drug; Lagnos ® , Argamate ® that contain...

1 大蔵製薬 (株) 研究開発第一部 (〠 611-0041 宇治市槙島町 十一 65-1) * 2 山形大学大学院理工学研究科機械システム工学専攻ソフ ト & ウェットマター工学研究室 (〠 992-8510 米沢市城南 4-3-16) * 3 岐阜薬科大学大学院薬学研究科薬科学専攻薬物送達学大 講座製剤学研究室 (〠 501-1196 岐阜市大学西 1-25-4)