Preparation of Extemporaneously diazepam Suppositories: in Vitro Release and Aging Study

Main Article Content

Nattha Kaewnopparat
Kwunchit Oungbho
Sanae Kaewnopparat
Theera Rittirod
Wipapom Rojanarat
Thanee Tessiri

Abstract

The objective of this study was to develop a fast-release extemporaneously diazepam suppository using pulverized diazepam tablet instead of diazepam powder. Four kinds of extemporaneously diazepam suppositories were formulated: 1) a conventional suppository with Witepsol H-15 as a base, 2) a conventional suppository with mixed polyethylene glycols (PEGs) as a base, 3) a hollow-type suppository with Witepsol H-15 as a base which contained pulverized diazepam in its cavity and 4) a hollow-type suppository with mixed PEGs as a base which contained pulverized diazepam in its cavity. The results of DSC thermograms indicated that diazepam was dissolved in Witepsol base and had strong affinity to this lipophilic base while diazepam dispersed in mixed PEGs base was still in the crystalline form. From the dissolution studies, the release of diazepam from suppository formulation no. 1, 3 and 4 was very slow. Diazepam suppository from formulation no. 2 exhibited the fastest release which complete dissolved after 30 minutes and gave the similar dissolution and permeation profiles compare to diazepam suppository using diazepam powder as the active ingredient. The content of diazepam from formulation no. 2 and the dissolution profiles after storage for 2 months did not significantly different from freshly prepared. Therefore, the extemporaneously diazepam conventional suppository which mixed PEGs as the base was found to be the most effective rapid-release formulation.

Downloads

Download data is not yet available.

Article Details

Section
Pharmacy

References

British Pharmacopoeia. London: The Stationary Office; 2001: p. 2015, A235.

Fitzgerald BJ, Okos AJ, Miller JW. Treatment of out-of-hospital status epilcpticus with diazepam rectal gel. Seizure 2003; 12:52-55.

Hosny EA, Abdeel-Hady SS, El-Tahir K. Formulation, in vitro release and ex vivo spasmolytic effects of mebeverine hydrochloride suppositories containing polycarbophil or polysorbate 80. Int J Pharm 1996;142:163-168.

Mura p, Manderioli A, Bramanti G et al. Properties of solid dispersions of naproxen in various polyethylene glycols. Drug Dev Ind Pharm 1996;22:909-916.

Tanaka M, Kuwahara E, Takahashi M et al. Enhanced rectal absorption of amphotericin B lyophilized with glycyrrhizinate in rabbits. Biol Pharm Bull 1998;21:853-857.

Wang X, Michoel A, Mooter GVD. Study of the phase behavior of polyethylene glycol 6000-itraconazole solid dispersions using DSC. Int J Pharm 2004; 272(1-2): 181-187.

Watanabe Y, Matsumoto Y, Baba K et al. Pharmaceutical evaluation of hollow type suppositories. IV. Improvement of bioavailability of propranolol in rabbits after rectal administration. J Pharmacobiodyn 1986;9:526-531.