Abstract
Purpose: A study was made of the effects of some bases and adjuvants on the physical and release properties of metronidazole suppositories with a view to providing more information for the optimization of the rectal formulation of metronidazole. Method: Suppositories (1g) containing 200mg of metronidazole each were prepared in witepsol (H15 and E75) and polyethylene glycol (PEG 2850 and 4650) bases, using different concentrations of Tween 80, sodium salicylate and methylcellulose as adjuvants. The setting time, solidification point and melting range of the suppositories were determined, along with their crushing strength, disintegration time and the time for 80% of metronidazole to be released from the suppositories (t80). Results: The ranking of setting time for the suppositories was witepsol H15 > PEG 2850 > witepsol E75 > PEG 4650, while the ranking of solidification point, melting range, crushing strength, disintegration time and the time for 80% of metronidazole to be released from the suppositories (t80) was the reverse of that for setting time. Optimal concentrations of Tween 80 and sodium salicylate were observed for the suppository formulations. Using Kitazawa plots, all formulations showed two dissolution rate constants, k1 and k2 intersecting at time t1, with formulations containing 5 to 20 % w /w of methylcellulose exhibiting a third dissolution rate constant, k3 intersecting with k2 at time t2. Conclusion: The physical and release properties of metronidazole suppositories are influenced considerably by the bases and adjuvants employed. Tween 80 and sodium salicylate can probably be used to formulate only immediate-release suppositories while methylcellulose can be useful for sustained-release metronidazole suppositories. Some insight into these inferences can be obtained from parameters derived from Kitazawa plots.
Highlights
Suppositories have been recognized as an alternative to the oral route in situations such as when the patient is comatose, unable to swallow or when the drug produces nausea or vomiting
It was considered of interest to study the effects of different formulation adjuvants with different properties on the physical and release properties of metronidazole in witepsol and polyethylene glycol (PEG) suppository formulations
The rankings of most of the physical and release parameters for the different suppository bases show that the bases can probably be employed to formulate metronidazole suppository formulations with a variety of physical and release properties for different purposes
Summary
Suppositories have been recognized as an alternative to the oral route in situations such as when the patient is comatose, unable to swallow or when the drug produces nausea or vomiting. Investigators have shown that the physical and release properties of many suppositories depend considerably on the physicochemical properties of the drug, suppository base and formulation adjuvants[1,5,6] and a lot of formulation work is normally required to optimise the properties of suppository preparations. In the case of metronidazole, which has been presented in suppository form[2,7,8,9] due to various factors, especially gastrointestinal disturbances and nausea when given orally[6,7], there have been reports of a lot of variability in drug release from different suppository formulations[2,7]. The present work was designed to investigate the effects of some formulation factors on the physical and release properties of metronidazole suppositories with a view to providing more information on the way to optimize the properties of the resulting suppositories. It was considered of interest to study the effects of different formulation adjuvants with different properties on the physical and release properties of metronidazole in witepsol and polyethylene glycol (PEG) suppository formulations
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