Typical Services Provided
Pharxmon Consulting, LLC does not perform laboratory measurements. Often, clients also do not have laboratories but rather manage analytical chemistry support of drug development entirely through CRO’s. Dr. Harmon is able to convey deep chemical and physical understanding of your drug molecule which then informs degradation behaviors, HPLC method selectivity needs, and excipient and formulation selection. Degradate/impurity structures are suggested early in program development. HPLC method/analytical troubleshooting issues are routinely encountered and rapidly solved.
Assessing realistic oxidative and hydrolytic susceptibilities of your drug substance
Oxidative sensitivity of a drug is often difficult to assess, in terms of, will you see oxidative degradation during drug product stability studies? Based simply on the drug molecular structure, Pharxmon Consulting can provide an assessment of oxidative and hydrolytic sensitivities. More accurate determination can be made after a set of simple, predictive solution-based forced stressing procedures (Ref. 9, 11, 6, 7, 16, 17) are carried out. Possible peak structures can be suggested. With simple unit mass resolution data, the likely structures of any resulting peaks are provided. A profile of potential real degradates is thus in hand.
Provide molecular rationale for HPLC stability indicating method, selectivity requirements
Armed with the predictive forced stress results and decades of HPLC method experience, Pharxmon Consulting can help focus clients on the relevant degradates, define the likely critical pairs, and remind clients how their drug molecules retention behavior will depend on various HPLC conditions. This information is shared with the CRO’s to better inform their HPLC method development efforts. In this way, well understood, rational, and appropriately selective HPLC Stability indicating methods result early in the pre-clinical space (Ref. 15).
Excipient screening and formulation selection guidance
Pharxmon Consulting has considerable experience in understanding how certain excipient impurities can drive oxidative degradation and form change (Ref. 7, 13, 18, 19, 22). Excipient screening HPLC studies can be wholistically understood and rationalized with regard to the molecules known degradation susceptibilities at this point, and optimum excipients (and thus formulations) can be selected.
Dissolution rate assessment and optimization
If the drug form is poorly soluble, dissolution of the drug from the formulation can be rate limiting and result in poor absorption. Understanding and optimizing the dissolution rate may become important. Pharxmon Consulting has considerable experience in “bio-relevant” dissolution procedures and understanding fundamental dissolution processes of conventional as well as amorphous dispersion-based formulations (Ref. 4, 5, 13). Specific bio-relevant dissolution measurements are suggested to the client. Formulation changes to enhance dissolution rates can be suggested to drive the highest possible absorption rates.
Drug Product Stability studies - degradate structural ID, mechanism of formation, mitigation strategy
Initial drug product stability studies that result in significant degradate peak growth under ICH conditions are often of concern. At this point, degradates appearing in drug product are typically known to be oxidative or hydrolytic; and detailed mechanisms of formations are known. Thus, appropriate mitigation strategies can be applied (specific antioxidants, excipient changes, etc.). Pharxmon Consulting assists clients in structural ID data interpretation and designs further simple experiments to confirm proof of structure. Similar assistance is often given to understanding impurities in the drug substance impurity profile.
HPLC method/analytical troubleshooting
HPLC is the workhorse analytical method for Pharxmon Consulting’s clients as they manage analytical development through their CRO’s. Thus, HPLC method problems and troubleshooting across various CRO’s is all too common (peak splitting, RRT shifting lab-to-lab, RT drifting, “ghost peaks”, etc.). Pharxmon Consulting LLC’s decades of experience in the laboratory running/developing HPLC methods for pharmaceuticals is leveraged to quickly resolve these analytical issues.