Rehydration of micronized tecovirimat monohydrate
Inventors
Tyavanagimatt, Shanthakumar R. • Reeves, Matthew • Samuel, N K Peter • PRIEBE, Steven • Tan, Ying • Hruby, Dennis E.
Assignees
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Publication Number
US-10716759-B2
Publication Date
2020-07-21
Expiration Date
Abstract
Disclosed are methods for hydration of ST-246 particles comprising exposing said particles to moisture by conveying volumes of air containing moisture.
Core Innovation
The invention relates to polymorph Form I monohydrate ST-246 particles that are micronized and partially dehydrated during an air-jet micronization process. The partial dehydration is associated with subsequent conversion to ST-246 polymorph Form V hemihydrate during storage, and the invention addresses maintaining stable ST-246 Form I monohydrate after micronization.
The method rehydrates dehydrated micronized ST-246 particles by exposing the particles to moisture. The exposure is carried out by conveying volumes of air having greater than 30% relative humidity to the particles, which restores stable monohydrate Form I and reduces or prevents formation of Form V hemihydrate during storage.
The approach uses humidity-dependent moisture reabsorption, including conveying humidified air with controlled relative humidity. Documented assessments include Karl Fischer measurements of moisture and structural assessments by XRPD and DSC, and the partial content further describes commercial-scale feasibility studies using Turbo-Screen to increase moisture while maintaining absence of Form V hemihydrate after accelerated storage.
Claims Coverage
The independent claim identifies a two-step inventive method comprising micronizing dehydrated ST-246 particles to a defined particle-size range and rehydrating them by moisture exposure using air with relative humidity greater than 30%. Dependent claims narrow where moisture exposure occurs among listed processing operations and add a polymorph-composition limitation excluding Form V hemihydrate.
Micronizing polymorph Form I monohydrate ST-246 using an air jet mill to obtain partially dehydrated particles
Micronizing polymorph Form I monohydrate ST-246 particles using an air jet mill to reduce particle size to D90<10 microns to obtain partially dehydrated polymorph Form I particles and/or polymorph Form V hemihydrate particles.
Rehydrating by conveying air with greater than 30% relative humidity
Rehydrating said micronized ST-246 particles by exposing said particles to moisture by conveying volumes of air having greater than 30% relative humidity to said particles.
Moisture exposure during a listed particle-processing step
The exposure of said particles to moisture occurs during one of several specified processing steps including forced-air high-throughput processing, classification/granulation, drying, sifting/scalping, de-dusting/de-lumping, mixing, or fluid-bed drying.
Moisture exposure during high-throughput forced air and screen-dependent classification
The exposure of ST-246 particles to moisture takes place during high-throughput forced air and screen-dependent classification.
Moisture exposure during high shear granulation
The exposure of ST-246 particles to moisture takes place during high shear granulation.
Micronized particles contain no Form V hemihydrate
The micronized ST-246 particles contain no ST-246 polymorph Form V hemihydrate particles.
Overall, the claim set covers micronizing polymorph Form I monohydrate ST-246 to D90<10 microns to produce partially dehydrated particles, followed by rehydration via air conveying with greater than 30% relative humidity. Dependent claims further constrain the location of moisture exposure to particular listed operations and optionally require that the micronized particles contain no Form V hemihydrate.
Stated Advantages
Restores stable monohydrate Form I after air-jet micronization-associated partial dehydration.
Rapidly reabsorbs moisture to the monohydrate level without significant particle size change, as described in the partial content.
Prevents or reduces formation of ST-246 polymorph Form V hemihydrate during storage, including absence of Form V after accelerated storage in the described Turbo-Screen studies.
Documented Applications
Reducing particle size of ST-246 using an air jet mill while addressing dehydration and preventing Form V formation during storage, including feasibility/optimization studies at commercial scale (Turbo-Screen pass studies).
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