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Secondary Blooming and Mottling in an Intravaginal Drug Release Product

This study was undertaken to determine the root cause of secondary blooming (surface progesterone) and mottling (translucent regions) in the CIDR insert. A stability study on CIDR inserts found that the alternative supplier silicone (Dow Corning silicone is used in normal manufacture) did not exhibit either secondary blooming or mottling, in agreement with previous work. There was no difference in ‘in vitro’ drug release rate between CIDR inserts made from the two silicone feedstocks. This silicone was found to have a higher ratio of low molecular weight cyclic silicone compounds to straight chain silicone compounds (Measured through detected ion ratios in the leachate by ESMS). The exact relationship between blooming and secondary mottling and this discovery remains unknown. Results from this research found that part B of the Dow Corning silicone was not responsible for causing secondary blooming and mottling in contrast to previous research. ESMS and GCMS results found that the Dow Corning part B had a more complex composition than of the samples from Dow Corning part A and alternative supplier silicone part A and part B. It was found that addition of a silicone crosslinker into the Dow Corning silicone, increased mottling, but not secondary blooming. Increasing the mixing of progesterone and liquid silicone decreased mottling (via a static mixer), but did not increase surface progesterone. The results from two studies into the packing of CIDR inserts immediately after manufacture were contradictory as one found a decrease in mottling from packing in line, while the other found no change in mottling. However there was no difference observed in surface progesterone levels between the packing conditions. Studies on the length of cure were also found to have no predictable effect on mottling. Studies on arresting the cooling cured silicone above, between and below the melting points of the α and β progesterone polymorphs found that pausing cooling after cure at ~135 °C resulted in decreased secondary blooming and mottling, and that pausing after cure at ~125 °C exhibited less secondary blooming. Neither DSC nor XRD was able to determine a polymorphic bias in progesterone cooled by this cooling process (β progesterone polymorph was in all but one case (that had an added reduction in normal cooling rate)). Studies (XRD and DSC) on the cooling rate of progesterone found that only with very slow cooling rates was the α progesterone polymorph formed. XRD studies also revealed that the mottled regions of CIDR inserts exhibit the β progesterone polymorph, whereas the α progesterone polymorph was detected in non-mottled regions. The mottled regions were found to continue to exhibit the same polymorph after removal of surface progesterone, whereas the non-mottled regions gave no detectable XRD peak intensity. The study found useful information to assist in the determination of the root cause of secondary blooming and mottling in CIDR inserts. However the root cause remains unknown.
Type of thesis
Waugh, B. A. (2006). Secondary Blooming and Mottling in an Intravaginal Drug Release Product (Thesis, Master of Philosophy (MPhil)). The University of Waikato, Hamilton, New Zealand. Retrieved from https://hdl.handle.net/10289/2331
The University of Waikato
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