| Summary: | New excipients increase new possibilities of the modifications in the composition of a compounded drugs. One of the examples is a Witepsol H15 suppository base registered in 2018 as an alternative to the previously used cocoa oil. The use of Witepsol H15 requires the determination of the replacement factors for active substances and excipients to calculate the optimal amount of this suppository base to prepare a certain number of suppositories. The classical method, which has been used so far, is based on the measurements of the mass of the suppositories with and without API, and the determination of the replacement factor using a calculation formula. Taking into account the differences between replacement coefficients resulting for example from a type and concentration of the active substance or excipient, the method of mixing and its parameters, it is reasonable to introduce an alternative calculation method based on the density measurements determined pycnometrically. Density measurements of excipients, APIs and selected medicinal products were carried out using the helium pycnometry method. Based on the ratio between density of the substrate to the API/excipient, the replacement coefficients were calculated. In total, two suppository bases (Witepsol H15 and Cacao oleum), 17 active substances, 2 excipients and 8 medicinal products were tested. The results were presented in tables, compared with available literature data and percentage differences were calculated.
In order to complete the practical information regarding use of Witepsol H15, the numerous test on the functional properties of the base were carried out, including: volume contraction, sensitivity to process factors, thermal changes during heating and cooling. The ability to reduce the volume of the base during solidification has been confirmed, which allows an easy withdrawal of the suppository from the mold before application. The average contraction for Witepsol H15 is 3.23%, which is about 3 times higher compared to cocoa oil (1.13%). An analysis of the behavior during cooling of Witepsol H15 heated to different temperatures, was carried out and it was found that the overheated base shows stepped thermal changes profile while solidifying. The profile of temperature changes of properly liquefied base is predictable and does not show dynamic changes. Based on the DSC data, the liquid fraction content of Witepsol H15 was calculated. The base heated previously to 45 °C contains more liquid components than the unheated base. A practical implication is the recommendation to not overheat the base in order to obtain proper liquefaction of the suppository mass, easy filling of molds and limitation in the sedimentation of ingredients in suppositories.
The results of performed studies confirm the usefulness of helium pycnometry to measure the density of substances and suppository bases, and to determine on their basis the displacement coefficients of active substances/excipients not included in the compendia so far. The helium pycnometry method enables the calculation of the displacement coefficient in the objective manner, independent of many factors, such as: base variability, preparation method, mixing parameters, content of API and excipients, size and load of the mixing container, conditions of solidification of the suppository mass. The replacement factors obtained in this way may be helpful in compounding practice. With the correct selection of mixing parameters, they lead to the obtainment of optimal amount of liquefied suppository mass necessary to fill the molds.
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