Lyophilised cMet Peptide Imaging Agent Formulation
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Solution Overview
Problem
The existing optical imaging agents, such as those described in WO2008/139207, have poor shelf life and stability in solution, leading to storage and degradation issues prior to intravenous injection, and require appropriate pH and tonicity for intravenous administration.
Innovation Solution
A lyophilised formulation comprising an active pharmaceutical ingredient (API) - cMet binding peptide, a buffering agent, and a lyoprotectant, which, when reconstituted, maintains a pH between approximately pH 6.8 and pH 9, enhancing stability and suitability for intravenous use.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If the imaging agent is stored in solution form, then it is ready for immediate intravenous administration, but it suffers from poor shelf life and degradation
Solution Approach 1:
The formulation is divided into separate components: a lyophilised cake containing the imaging agent and stabilisers, and a separate reconstitution solution. This segmentation allows the imaging agent to be stored in a stable dry state while enabling ready preparation for administration through simple reconstitution with the provided solution.
Solution Approach 2:
The imaging agent is pre-formulated with buffering agents and lyoprotectants in a lyophilised state, and a reconstitution solution is prepared in advance. This preliminary preparation ensures that when the agent is reconstituted, it immediately achieves the correct pH and stability conditions for intravenous administration without requiring further adjustment.
2Reliability
If the imaging agent is formulated for stability, then shelf life is extended, but pH and tonicity adjustments are required for intravenous use
Solution Approach 1:
The formulation merges multiple functions into a single integrated system: the lyophilised cake contains the imaging agent plus buffering agents and lyoprotectants, while the reconstitution solution provides both solvent and tonicity adjustment. This combination ensures that a single reconstitution step simultaneously achieves dissolution, pH adjustment, and tonicity optimisation for intravenous compatibility.
Solution Approach 2:
The reconstitution solution serves multiple purposes: it acts as a solvent for dissolving the lyophilised cake, a buffering agent to achieve physiological pH, and a tonicity adjuster to make the final formulation suitable for intravenous administration. This multi-functionality reduces the number of separate steps and components needed.
3Quantity of substance
If the imaging agent is reconstituted at high concentration, then dosage volume is reduced, but agglomeration and heterogeneity occur
Solution Approach 1:
Lyoprotectants such as sugars or sugar alcohols are included in the lyophilised formulation as intermediary substances. These intermediaries prevent agglomeration of the imaging agent molecules during lyophilisation and reconstitution, enabling the preparation of high-concentration homogeneous solutions suitable for intravenous administration without precipitation or aggregation.
Data Source
Figure 1
AI summary
There is described formulations for human or animal administration and to a method of preparation thereof. In particular, there is described more stable pharmaceutical formulations, such as those for intravenous administration, and to a method of preparation thereof. There are also described lyophilised formulations having an active pharmaceutical ingredient (API), a buffering agent and a lyoprotectant, wherein the API is an imaging agent comprising at least one cMet binding peptide, suitable for optically imaging the mammalian body in vivo. Also described are a method of preparing a lyophilised formulation, a pharmaceutical composition, and a kit for the preparation of the pharmaceutical composition. Further described are methods of imaging using the formulation or pharmaceutical composition, such as in detection, diagnosis, surgery, staging, treatment, monitoring of treatment, monitoring of disease progression or monitoring therapy of conditions such as cancer.