Lyophilized immunoglobulin formulations and methods of preparation
A freeze-dried preparation and freeze-drying technology are applied in the field of pharmaceutical preparations of immunoglobulins, which can solve the problems of affecting the stability of preparations and difficult to determine which result is
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0092] A comparative study of a high-concentration reconstituted lyophilized and liquid formulation of natalizumab was performed in cynomolgus monkeys. The results of the study showed that the reconstituted lyophilized formulation of natalizumab produced the expected pharmacokinetic and pharmacodynamic profile very similar to the liquid formulation.
[0093] High-concentration liquid formulations and reconstituted lyophilized formulations of natalizumab were evaluated to compare their corresponding pharmacokinetic / pharmacodynamic profiles, relative bioavailability, and subcutaneous (SC) and intramuscular (IM) administration. Local tolerance after drug administration. Both the liquid (150 mg / mL) and the reconstituted lyophilized (120 mg / mL) high-strength formulation were each administered via the extravascular route on Day 1 and their pharmacokinetic / pharmacodynamic profiles assessed on Day 36 . A single 30 mg dose of commercial liquid natalizumab was also administered on Day...
Embodiment 3
[0250] As demonstrated below, three formulations with slightly different initial protein concentrations were successfully lyophilized and showed excellent stability when stored at 5°C for 6 months. The stability of these formulations when stored at 40°C for 8 weeks was comparable to that previously observed. Stability was also excellent for formulations stored at 5°C for 6 months prior to lyophilization and for reconstituted solutions stored at 5°C or 25°C for one week. A starting concentration of 40 mg / mL showed slightly better stability and better reconstitution properties than the other formulations. However, reconstitution of this formulation did allow for a deliverable dose of 1 mL at 150 mg / mL.
[0251] Material
[0252] The table below lists materials and their sources.
[0253] Table 22
[0254] thing
manufacturer
Bulk Natalizumab
(77.4mg / mL)
Elan
Sucrose (96mg / mL)
Elan
1% PS80
Elan
60mM histidine
Ela...
Embodiment 4
[0345] The aim of this study was to use an experimental design to determine the effect of final protein concentration and optimal protein to sucrose ratio on lyophilization of natalizumab to prevent and minimize aggregate formation.
[0346] Experimental Design Parameters
[0347] Final protein concentrations of 40 mg / mL to 160 mg / mL were examined, with protein to sucrose ratios of 1:100 to 1:500. Polysorbate 80 levels were kept constant at an amount of 0.01% per 10 mg / mL protein and histidine was kept constant at 10 mM per 40 mg / mL protein. The starting protein concentration (before lyophilization) will be 40 mg / mL. Vials were filled at 2 mL and then reconstituted to the desired final protein concentration.
[0348] Short-term stability at 40 °C for 0, 2, 4 and 6 weeks was examined.
[0349] program:
[0350] 1. Diafilter the current formulation against one of the following buffers. Then ultrafilter to protein concentration >40mg / mL. Measure protein concentration and di...
PUM
| Property | Measurement | Unit |
|---|---|---|
| osmolarity | aaaaa | aaaaa |
Abstract
Description
Claims
Application Information
Login to View More