title: Secondary Blooming and Mottling in an Intravaginal Drug Release Product

authors: Waugh, Brendan Arthur

subjects: progesterone

abstract: 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.

text: 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.

year: 2006

title: Aeroconservation – Challenges for law and policy

authors: Wallace, Philippa Jane

abstract: Airspace conservation (aeroconservation) is a relative latecomer to ecosystem management, despite intensifying threats to birds, bats and invertebrates in the habitat. This article demonstrates the geographies of threats and examines gaps in law and policy responses. Commonly treated at law, and in fact, as an extension of terrestrial or marine spaces, recognition of air as habitat and related conservation protection is rare. In addition, management is confounded by the dynamic, three-dimensional and indivisible nature of airspace, by wildlife and aircraft mobility, and by temporal features. Regulation of airspace and patterns of spatial activity are dominated by aircraft traffic control and related transport imperatives to the exclusion of wildlife protection. Where strategic planning mechanisms are applied, they are often tied to amorphous definitions of habitat, rely upon terrestrial habitat protection for their expression or are reflected as two-dimensional notations on a map. Recommendations to enhance protection for co-existence include transforming the approach to airspace and adopting integrated, strategic and three-dimensional approaches.

text: Aeroconservation – Challenges for law and policy Airspace conservation (aeroconservation) is a relative latecomer to ecosystem management, despite intensifying threats to birds, bats and invertebrates in the habitat. This article demonstrates the geographies of threats and examines gaps in law and policy responses. Commonly treated at law, and in fact, as an extension of terrestrial or marine spaces, recognition of air as habitat and related conservation protection is rare. In addition, management is confounded by the dynamic, three-dimensional and indivisible nature of airspace, by wildlife and aircraft mobility, and by temporal features. Regulation of airspace and patterns of spatial activity are dominated by aircraft traffic control and related transport imperatives to the exclusion of wildlife protection. Where strategic planning mechanisms are applied, they are often tied to amorphous definitions of habitat, rely upon terrestrial habitat protection for their expression or are reflected as two-dimensional notations on a map. Recommendations to enhance protection for co-existence include transforming the approach to airspace and adopting integrated, strategic and three-dimensional approaches.

year: 2019

title: Te Raupatu o Tauranga Moana = The confiscation of Tauranga lands. [Volume 1]

authors: Stokes, Evelyn

subjects: Tauranga lands

abstract: A report providing a historical and geographical overview on the confiscation of Tauranga lands. In two volumes, volume one comprises a narrative of the events described as the raupatu, the confiscation of lands in the Tauranga Moana tribal area under the New Zealand Settlements Act 1863.  Volume two is a collection of documents, edited and annotated which were compiled in support of the report. These documents include personal accounts, tribal history, land purchases, lands returned and crown transactions.

text: Te Raupatu o Tauranga Moana = The confiscation of Tauranga lands. [Volume 1] A report providing a historical and geographical overview on the confiscation of Tauranga lands. In two volumes, volume one comprises a narrative of the events described as the raupatu, the confiscation of lands in the Tauranga Moana tribal area under the New Zealand Settlements Act 1863.  Volume two is a collection of documents, edited and annotated which were compiled in support of the report. These documents include personal accounts, tribal history, land purchases, lands returned and crown transactions.

year: 1990