Scale-up prospects
DPV is manufactured commercially through a well-defined synthetic chemical process and undergoes a micronisation procedure to improve drug dispersion within the silicon intravaginal ring.
The current DPV ring formulation (Ring-004) contains 25mg of micronised drug product and is produced with NuSil™ DDU-4870 silicone elastomer using addition-curing to prevent the formation of undesirable volatile alcohol by-products. This formulation provides high pharmacokinetic exposure with low overall manufacturing costs.
Novel additive manufacturing techniques (e.g. APF) could provide new formulations.
Tentative equipment list for manufacturing
For ring manufacture: Injection molding machine, mixer, automated inspection and packaging machines.
Manufacturing
Manufacturing is a non-standard four stage workflow process: (1) preparation of the master batch, (2) pre-mix formation, (3) ring construction using injection addition-curing, and (4) packaging/inspection.
For DPV Compound: stability testing indicates that the chemical compound can be stored for up to 6 months at 40ºC and 96 months at 25ºC in the pre-specified commercial packaging. DPV is photo-stable.
For Finished Ring Product: stability testing shows that the product can be stored for 48 months at 30ºC. The DPV ring product is photosensitive and should be stored away from light sources.
Specific analytical instrument required for characterization of formulation
For DPV Compound: HPLC (determine chemical purity), GC (residual solvents), laser diffraction (determine particle size), Karl Fischer titration (determine water content) and FT-IR & DSC (chemical identification).
For Finished Ring Product: HPLC (determine dissolution, content uniformity and degradation products), compression testing machine (determine tensile and compression properties).
