FORMULATION OF DIAZEPAM SUPPOSITORIES WITH HYDROPHILIC AND LIPOPHILIC BASES
Keywords:
diazepam, suppositories, formulationsAbstract
Diazepam belongs to a class of a long-acting benzodiazepine with anticonvulsant, sedative, and anxiolytic
properties. Because of its rapid absorption it is a commonly used drug for the treatment of acute recurrent epileptic
seizures that occur at children.
It is also used for the treatment of acute febrile convulsions and as the drug of choice diazepam is given
intravenously to produce the effect more quickly. But the intravenous method of application requires professional
competence from medical personnel. Due to the difficult swallowing during a seizures, the oral and sublingual
administration of diazepam in that case is impossible. Rectal formulations with diazepam stand out as a type of drug
administration that achieves rapid application and timely action. Diazepam rectal solutions are not widely used
because of the possibility of incorrect dosing and rectal leakage. Suppositories as a pharmaceutical dosage form are
the drug of choice for administering diazepam. Absorption of the active component after rectal administration
depends on: the melting or dissolution of the suppository and the diffusion of the active substance and the
penetration of the dissolved molecules through the epithelial cells of the mucous membrane of the rectum. In the
formulation of suppositories, the solubility of the active component in the base plays a major role. The bases used in
manufacturing the suppositories can be hydrophilic or lipophilic.
The aim of this study is to define a base of choice for the manufacture of diazepam suppositories, following the
pharmaceutical-technological manufacturing process and the physico-chemical properties of the obtained
suppositories. Suppositories were made with two types of bases, hydrophilic and lipophilic. Macrogol (Polyethylene
glycol-PEG) with a different molecular weight is used as a hydrophilic base. During the technological development,
three different formulations of suppositories were made with diazepam and a hydrophilic base Macrogol (PEG) with
different molecular mass in different ratio.
The first formulation consists of diazepam and Macrogol 6000, the second diazepam and Macrogol 6000- 40% and
PEG 1500- 60% and the third of diazepam and Macrogol 6000 - 40%, Macrogol 1500 - 40% and Macrogol 400 -
20%. Lipophilic base Withepsol H15 was used in the other formulations, and one formulation was made with
diazepam and Withepsol H15, and one formulation with diazepam and Withepsol H15 + Tween 80.
Based on the obtained results, it is estimated that the third developed formulation, which in its composition has
diazepam and a hydrophilic base in the following ratio Macrogol 6000 - 40%, Macrogol 1500 - 40% and Macrogol
400 - 20%, shows the best physico-chemical characteristics in relation to the rest.
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