Methods of assessing suitability of use of pharmaceutical compositions of albumin and poorly water soluble drug
Inventors
Peykov, Viktor • Foss, Willard • Pierce, Daniel W. • Desai, Neil P.
Assignees
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Publication Number
US-11320416-B1
Publication Date
2022-05-03
Expiration Date
Abstract
The present invention provides methods of assessing suitability of a pharmaceutical composition for medical use. The pharmaceutical composition comprises nanoparticles comprising rapamycin coated with albumin and a non-nanoparticle portion comprising albumin and rapamycin.
Core Innovation
The invention relates to validating a commercial batch and/or assessing suitability for medical use in a human individual of a pharmaceutical composition comprising nanoparticles comprising rapamycin coated with a coating comprising albumin, and a non-nanoparticle portion comprising albumin and rapamycin. A sample is obtained from the commercial batch, the nanoparticles are separated from the non-nanoparticle portion, and a weight percentage of albumin in the form of albumin polymers in the coating of the separated nanoparticles among the total albumin in the coating of the separated nanoparticles is measured.
Suitability for medical use is based on the measured weight percentage of albumin polymers being from about 15% to about 40% as indicative of suitability for medical use. The commercial batch is validated if the pharmaceutical composition is suitable for medical use, and the same separation and measurement concept is used to assess suitability in a human individual.
The disclosure additionally describes suitability assessment using albumin oligomeric composition on nanoparticles and multi-parameter quality control of the albumin-rapamycin nanoparticle pharmaceutical composition. This includes albumin monomer/dimer/oligomer/polymer fractions and quantitative ranges, rapamycin crystallinity and solubility, rapamycin recovery after [procedural detail omitted for safety], nanoparticle morphology, coating thickness, surface-to-volume ratio, particle size distribution/polydispersity/size span, zeta potential, and stability after storage.
Claims Coverage
The document includes two independent claims, both centered on validating or assessing suitability for medical use in a human individual using separation of nanoparticles from a non-nanoparticle portion and a quantitative albumin species criterion expressed as a weight percentage of albumin polymers in the nanoparticle coating among total coating albumin. Across the independent claims, the core inventive features comprise sampling, nanoparticle/non-nanoparticle separation, measuring albumin polymer weight percentage in the coating, and using the about 15% to about 40% range as an indicator of suitability for medical use.
Validated batch by albumin polymer fraction in nanoparticle coating
Obtaining a sample from a commercial batch of a pharmaceutical composition comprising rapamycin-coated nanoparticles with an albumin coating and a non-nanoparticle portion comprising albumin and rapamycin; separating the nanoparticles from the non-nanoparticle portion; measuring a weight percentage of albumin in the form of albumin polymers in the coating of the separated nanoparticles among total albumin in the coating; and validating the commercial batch if the weight percentage of albumin polymers among total coating albumin is from about 15% to about 40% and is indicative of suitability for medical use.
Assess suitability by albumin polymer fraction in nanoparticle coating
Obtaining a sample from a commercial batch of a pharmaceutical composition comprising rapamycin-coated nanoparticles with an albumin coating and a non-nanoparticle portion comprising albumin and rapamycin; processing the sample to assess suitability by separating the nanoparticles from the non-nanoparticle portion; measuring a weight percentage of albumin in the form of albumin polymers in the coating of the separated nanoparticles among total albumin in the coating; and assessing suitability when the weight percentage is from about 15% to about 40% indicative of suitability for medical use in a human individual.
Both independent claims use the same suitability-defining measurement: the weight percentage of albumin in the form of albumin polymers in the coating of separated rapamycin-coated nanoparticles among the total coating albumin, with suitability indicated by a range of about 15% to about 40%. One claim further includes validating the commercial batch if suitable, while the other focuses on processing to assess suitability.
Stated Advantages
Enables validating or assessing the suitability of a commercial batch or sample of a rapamycin-coated albumin nanoparticle pharmaceutical composition for medical use in a human individual based on an indicative albumin-polymer weight percentage range.
The albumin oligomeric status on the nanoparticles is described as relating to stability, solubility, dissolution, and in vivo distribution.
Rapamycin radial tumor distribution is described as being enhanced relative to a solvent DMSO control, with a greater spread than the control within about 24 h after tumor injection.
Documented Applications
Validating a commercial batch of an albumin-coated rapamycin nanoparticle pharmaceutical composition for medical use in a human individual.
Processing a sample from a commercial batch of an albumin-coated rapamycin nanoparticle pharmaceutical composition to assess suitability for medical use in a human individual.
Rapamycin radial tumor distribution relative to a solvent DMSO control.
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