Development of an Easy to Use Oral Transmucosal Formulation with Superior Absorption as an Alternative to Injectable Drugs


Hideki SAKAI

【Research Theme】

Application of Injectable and Oral Drugs to Transmucosal Formulations

【Research Background】

Characteristics of oral transmucosal formulations include the ability to prevent first-pass effects, an immediate effect compared to oral drugs, and the ability to avoid pain associated with injection and the risk of adverse reactions in the event of accidental administration.

Kyukyu Pharmacutical Co., Ltd. (Headquarters: Imizu City, Toyama Prefecture) is a company with creative technologies that has succeeded in commercializing the world’s first “oral film formulation” containing the active ingredient in a form only a few tens of microns thick (1 micron is 1/1,000 of a millimeter).

In Japan, patches of the synthetic opioid fentanyl are used to relieve pain associated with cancer. Nasal drops and auto-injectors (the intramuscular route) of the opioid antagonist naloxone are used in other countries to rapidly respond to adverse reactions, such as respiratory depression, caused by fentanyl overdoses. And in Japan, it will become even more important to avoid risks during palliation of cancer pain at home.

When nasal drops are used in an emergency the following may occur: 1) There is a great deal of variation from dose to dose, even with an individual patient; 2) there are individual differences in the flow of administered drug solutions through the nasal cavity; 3) it is not easy for caregivers to accurately give nasal drops to patients. However, oral film formulations may overcome the above disadvantages of nasal drops.

【Research Details】

In this study, we are focusing on naloxone, an opioid antagonist, with the goal of commercializing an oral film formulation that offers significant benefits and advantages to patients. We are also investigating penetration enhancers to improve the absorption of drugs that are not readily absorbed through the oral mucosa. The School of Pharmacy and Pharmaceutical Sciences at the University of Toyama, Kyukyu pharmacutical Co., Ltd., and Toyama University Hospital are working closely together for these purposes. Specific studies include the following:

1) Kyukyu Pharmacutical Co., Ltd. is making various oral film formulations containing naloxone for use on laboratory animals and specified clinical trials on test subjects.
2) The School of Pharmacy and Pharmaceutical Sciences at the University of Toyama is conducting naloxone penetration experiments on the oral mucosa of laboratory animals (in vivo oral mucosa of rabbits and isolated buccal pouch mucosa of hamsters) to study the effects of penetration enhancers on naloxone penetration, etc.
3)A non-clinical cumulative oral irritation study of naloxone formulation in rabbits and the measurement of the blood concentration of naloxone formulation in oral mucosa administrations, also using rabbits, were carried out at a facility in compliance with GLP (good laboratory practice).
4) The specified clinical trial “Clinical Pharmacology Study of Buccal Transmucosal Formulation with Naloxone Hydrochloride” at Toyama University Hospital was published on the jRCT website on December 14, 2022 (clinical study protocol number: jRCTs041220104). Based on this, a specified clinical trial has been conducted at Toyama University Hospital since January 2023.

【Future Prospects】

In the future, we would like to establish an evaluation system that can predict pharmacokinetics, etc. in humans based on the results of studies of transoral mucosal film formulations in rabbits. We would also like to examine the implementation of an oral film formulation containing naloxone.