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Drug Res (Stuttg) 2018; 68(10): 560-566
DOI: 10.1055/a-0589-9886
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Preparation and Evaluation of Midazolam Rectal Gel in vitro and in vivo

Xiaojia Chen
1   Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, Beijing, China
,
Wanqin Li
2   School of Preclinical Medicine, Beijing University of Chinese Medicine, Beijing, China
,
Ying Li
1   Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, Beijing, China
3   State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing,China
,
Fei Guo
1   Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, Beijing, China
,
Hui Zhang
1   Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, Beijing, China
,
Jing Gao
1   Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, Beijing, China
,
Jianxu Sun
1   Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, Beijing, China
,
Aiping Zheng
1   Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, Beijing, China
3   State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing,China
› Author Affiliations
Further Information

Publication History

received 25 October 2017

accepted 09 March 2018

Publication Date:
09 April 2018 (online)

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Abstract

Midazolam has been successfully used for sedation, which the tablets, injections and oral solutions were available in market. However, the oral bioavailability of midazolam is less due to the first effect, while injection formulation has a low patient compliance. The purpose of this study was to obtain midazolam rectal gel to meet the production and market requirements. We evaluated the in vitro release behavior of midazolam powder, a physical mixture of midazolam and HPMC, and midazolam gel. The results showed that the midazolam gel has superior release degree compared to the other. Correspondingly, midazolam gel produced relevant plasma concentrations result in the rats. At the same dose (1 mg/kg), the Cmax and AUC (0-t) of midazolam after administration of the midazolam rectal gel were 8-10 times higher than that of the oral solution. The midazolam rectal gel was evaluated for physico-chemical tests including pH, viscosity, drug content at 40°C /75%RH (relative humidity) for 180 days (6 months). It provides information about the shelf lives of medicine, as well as the conditions for their storage. Rectum irritation test demonstrated that frequent application of midazolam rectal gel did not induce rectal mucosal damage. In conclusion, midazolam rectal gel was a potential new dosage form, which could alleviate the feeling of alien, discomfort and refusal during application of the patients. It was likely to be a more convenient and effective sedative medicine form specifically for infants and children.

Key words

midazolam - rectal gel - in vitro release - pharmacokinetic - rectal irritation
 

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