Timely Phase I Clinical Trials
In today’s market, pharmaceutical companies are struggling to do more with less. With diminishing resources, patent expiry, and increased competition, companies are under pressure to reach critical drug development milestones faster, in spite of candidate chemical and physical challenges. To make matters worse, oftentimes there are limited quantities of active pharmaceutical ingredient (API) available for adequate development in Phase 1. In light of this fact, CoreRx offers you several drug development approaches, customized to align with your corporate goals. It is more than just getting into the clinic faster. One must view drug development from a holistic perspective.
 API in bottle, powder in bottle, API into capsule, and traditional formulations are all approaches to consider for “first-in-man” phase 1 clinical trials. CoreRx capabilities & scientific depth encompass all available drug development options for expedited first-in-man studies. Whether your compound API is in short supply, has excipient compatibility issues, is unstable, or has solubility issues, CoreRx scientists can effectively deliver the solution that meets your budgetary and more importantly, your timeline needs. Depending upon your unique situation, CoreRx can use the following approaches.
API in bottle
Advantages
 No need for excipients
No formulation development
Minimal analytical development
Simplified stability testing
Minimized API usage
Wide range of dosage strengths |
Disadvantages
Clinic preparation time
Solubility issues may arise
Taste Masking may be difficult
Patient convenience may be compromised
|
Powder in bottle
Advantages
Wide range of dosage strengths
Minimal API Characterization
Use with Limited API availability
Added excipients can help with stability and taste masking |
Disadvantages
Longer Manufacturing Time
Clinic Preparation Time
Development of matching placebo needed
Additional analytical development required
|
API in capsule
A common approach for phase 1 supplies is weighing API into capsules. In many cases, the overall development timelines may be reduced by as much as six months, by reducing formulation time as well as some analytical development & stability testing. Additionally, placebo development is straightforward.
Following this approach is common for many pharmaceutical companies, as it is a “quick fix” option for supplying drug product to meet aggressive Phase I clinical study start dates. Dispensing API in capsules can be done by hand, semi-automated (utilizing a Quantos® or Xcelodose ® system), or have a fully automated approach using the Symyx Powdernium® benchtop *.
Although the API in capsule approach can be a timesaver, getting you into clinical studies sooner, but it will not eliminate the need to conduct formulation development and process optimization. It is therefore critical to weigh carefully the impact on the overall development plan (as well as cost and time) of using neat drug substance filled capsules/vials vs. a formulated product in early studies: A whitepaper discussing all of these points will be available in Q4 2009
Advantages
Short Manufacturing Time
Minimal API Characterization
Use with Limited API availability
Taste masking not necessary
Minimal Analytical Development |
Disadvantages
Increased overall drug development costs
Increase overall development time
Development of matching placebo needed
Not suitable for all API’s
Possible capsule compatibility issues
|
Formulated productProvided that there is ample time for prototype development, and the API synthesis does not change, a formulated product approach can have advantages. Having a formulated product in Phase 1 can ease the transition into Phase 2 studies, saving time. For controlled release formulations in Phase 1, developing a formulated product is the only option. For water insoluble compounds, liquid capsules or commonly utilized. As with all development work, upfront time & energy will be necessary, such as pre-formulation, excipient compatibility, analytical methods development, and stability testing. The downside is that the additional work will take time and money. It is a matter of pay now or pay later.
Advantages
Wide range of dosage strengths
Decreases overall development time
Decreased overall development costs
Added excipients can help with stability and taste masking |
Disadvantages
Longer Development & Manufacturing Time
Excipient Compatibility & Preformulation needed
Development of matching placebo needed
Additional analytical development required
|
Unfortunately, there is no single formulation approach that will fit every API. CoreRx will help you evaluate the advantages and disadvantages of each approach, depending upon the compound in question, as well as your overall project goals regarding time, budget, and API availability.
*For further information on capsule filling equipment go to our Resources Page |
