OHKURA Pharmaceutical Co., Ltd.

This study evaluates the potential of oral jelly formulations as supersaturable drug delivery systems for drugs with pH-dependent solubility, particularly in overcoming changes in gastric pH due to aging or medications.We prepared an oral jelly formulation of dipyridamole, a basic drug, by acidifying the jelly to pH 3.The stability of the acidified jelly was assessed over 28 days, with no precipitationFor comparison, a drug suspension and a neutral jelly were also tested.In vitro dissolution tests were conducted using 200 mL of Japanese Pharmacopoeia (JP) test fluids 2 (pH 6.8).Addnl., in vivo intestinal administration studies, bypassing gastric dissolution, were performed in rats to assess dipyridamole absorption.The acidified jelly showed a rapid, supersaturated dissolution profile in vitro.In vivo, the area under the curve (AUC) of dipyridamole from the acidified jelly was about 13 times higher than that of the suspension or neutral jelly.An alkalized jelly of telmisartan, an amphoteric drug, was also prepared at pH 10, showing a supersaturable dissolution profile in vitro and enhanced absorption in vivo.Acidified and alkalized jellies effectively serve as supersaturable formulations for basic and amphoteric drugs, with potential to improve oral absorption even under elevated gastric pH.

This study aims to clarify the process of oral drug absorption from jelly formulations. Agar and pectin-based jellies containing drugs with different membrane permeability (high: antipyrine [ANT], medium: metoprolol [MET], low: atenolol [ATE]) were prepared and tested for in vitro drug release and in vivo drug absorption in rats. All drugs showed similar release profiles in vitro from both jelly formulations, except for the faster release from pectin jelly at neutral pH. In contrast, in vivo absorption of ATE but not of ANT from jelly formulations was significantly lower than from solution. Absorption of ATE and MET was low from agar jelly after oral administration, whereas additional water intake significantly increased the absorption. The process of drug absorption was described by the compartmental model consisting of jelly, intestinal fluid, and blood compartments. Drugs in the jelly diffuse into the intestinal fluid and then permeate the intestinal membrane. By considering the rate-limiting process, membrane permeability-dependent drug absorption from agar jelly and the effects of water intake were identified. In conclusion, jelly formulations may potentially decrease and delay drug oral absorption, especially of poorly permeable drugs. Intestinal fluid volume is one of the important factors to control the drug absorption.

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.