The objective of this study was to evaluate the stability of diazoxide in extemporaneously compounded oral suspensions. Oral suspensions of diazoxide 10 mg/mL were prepared from either bulk drug or capsules dispersed in either Oral Mix or Oral Mix Sugar Free. These suspensions were stored at 5°C and 25°C/60%RH in bottles and oral syringes for a total of 90 days. At predetermined time intervals, suspensions were inspected for homogeneity, color or odor change; the pH was measured and the concentration of diazoxide was evaluated by ultraviolet detection using a stability-indicating high pressure liquid chromatography method. All preparations were demonstrated to be chemically stable for at least 90 days.
Background
Melatonin is commonly used to treat insomnia, sleep disturbance or hyperactivity disorders. It can be administered in paediatric patients as oral formulations prepared using either bulk powder or commercial products. Few studies have evaluated the stability of these oral formulations, but some storage conditions information may be lacking and a need has been identified for additional stability studies.
Aim
The aim of this research was to study the stability of extemporaneously prepared oral suspensions of melatonin (2 mg/mL), prepared from pure drug powder or commercial tablets using a proprietary dye‐free oral vehicle: Oral Mix SF (Medisca Pharmaceutique Inc.).
Method
Two melatonin oral liquid preparations were formulated: (a) tablets in Oral Mix SF and (b) pure drug powder in Oral Mix SF. Preparations were stored at room temperature (23–27°C) as well as under refrigeration (3–5°C) in amber plastic syringes (PreciseDose Dispenser™, Medisca Pharmaceutique Inc.) and amber polyethylene terephthalate (PET) bottles with appropriate closures for a period of 90 days. Preparations were assessed using a validated stability‐indicating high‐performance liquid chromatography method. Beyond use dates were evaluated by statistical analysis of the overall degradation trend.
Results
All preparations were physically and chemically stable for at least 90 days in all storage conditions at room temperature and under refrigeration.
Conclusion
Results showed that compared to other vehicles, these suspensions had equivalent stability, indicating that Oral Mix SF is a viable dye‐free and sugar‐free alternative for extemporaneous compounding of melatonin.
Spray-dried high-amylose sodium carboxymethyl starch (SD HASCA) is a promising pharmaceutical excipient for sustained-release (SR) matrix tablets produced by direct compression. The presence of α-amylase in the gastrointestinal tract and the variations of the gastric residence time of non-disintegrating dosage forms may affect the presystemic metabolism of this excipient and, consequently, the drug-release profile from formulations produced with SD HASCA. In this study, the influence of α-amylase and the residence time in acidic conditions on the drug-release profile was evaluated for a once-daily acetaminophen formulation (Acetaminophen SR) and a once-daily tramadol hydrochloride formulation (Tramadol SR). Both formulations were based on SD HASCA. α-Amylase concentrations ranging from 0 IU/L to 20000 IU/L did not significantly affect the drug-release profiles of acetaminophen and tramadol hydrochloride from SD HASCA tablets (f2 > 50) for all but only one of the studied conditions (f2 = 47). Moreover, the drug-release properties from both SD HASCA formulations were not significantly different when the residence time in acidic medium was 1 h or 3 h. An increase in α-amylase concentration led to an increase in the importance of polymer erosion as the main mechanism of drug-release instead of drug diffusion, for both formulations and both residence times, even if release profiles remained comparable. As such, it is expected that α-amylase concentration and residence time in the stomach will not clinically affect the performance of both SD HASCA SR formulations, even if the mechanism of release itself may be affected.
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