More and more however, the industry is using the BCS as a tool in drug product development. This system can be used to flag drugs that should not be tested clinically unless appropriate formulation strategies are employed see Figure 1.
For example, a BCS Class II compound permeable but relatively insoluble would likely not be a good clinical candidate without the use of enhanced formulation techniques aimed at increasing solubility or rate of dissolution.
Various schemes exist that attempt to funnel a given active pharmaceutical ingredient API towards a particular drug delivery technique based on the BCS category. Still, most approaches remain fragmented in their methodology, ignoring commercially and biologically important factors. The BCS can, however, when integrated with other information, serve as an effective tool for efficient drug development.
One school of thought is that first in human FIH drug dosage forms should be designed to maximize bioavailability. The FIH dosage form should be a logical step towards commercialization and not simply a stop gap to facilitate data acquisition. For other compounds, effective dosage forms present greater challenges. Although designed originally to classify APIs by their oral bioavailability, when properly augmented the BCS can be used as a key component of an algorithm to guide drug delivery system design for any route of administration.
Permeability can be determined a number of ways but is most often done using Caco-2 cell lines, an assay that lends itself to high throughput automation. In this system a monolayer of cells is grown and drug permeation from the drug donor apical side to the acceptor basolateral side compartments is assessed, usually by direct UV or LC-MS assay.
Potential issues with Caco-2 based systems range from variation from in vivo in transport mechanisms to drug interactions with the apparatus itself. Commercial companies focused on this assay have developed multiple approaches to alleviate these issues, but a discussion on the subject is beyond the scope of this technical brief. As a drug candidate moves up the development ladder, developers will often confirm and refine their BCS assessments with increasingly complex in vivo models.
An important factor to remember with the BCS is that it accounts for potency in that solubility and permeability are relative to clinical dose. Again, oral dosing is assumed in the testing design. It is commonly recognized that most new drugs present formulation challenges. Older drugs as compared to newer ones generally have higher solubilities.
In practice, low solubility is the most common theme encountered. It should be noted that not every drug is classified the same by each investigator. The variability can be due to a number of things including the way permeability is measured. As above, in vivo permeability is impacted by, among other things, drug transporters. Both uptake and efflux transporters exist and can contribute to the differences seen by the various techniques. Sometimes the physicochemical and physiologic mechanisms do not allow this and alternatives such as oral suspensions or solutions are pursued.
Other times, the target and additional factors dictate that a non-oral dosage form is most sensible. Examples include localized delivery of female hormones, nasal allergy preparations, ocular therapeutics, and combination products aimed at prolonged drug release. In all these cases, even though not orally dosed, the concepts inherent in the BCS can be important tools in dosage form design.
Having a pre-defined system in which one can make decisions based on data is necessary for efficient drug development. Inputs into such a system include, in addition to BCS class, a detailed solubility profile, polymorph status, desired dosage form, target dose and dosing regimen, drug stability, excipient compatibility, and knowledge of transporter and metabolic pathways.
Non-technical factors that, as a practical matter, need to be considered are such things as cost, intellectual property and distribution chain limitations. Integration of these into a methodical systematic approach will maximize the chances of a successful outcome. One thing that the BCS has gotten right, however, is its limit on conference participation.
No more than two teams from the same conference can be BCS eligible unless the No. Since that is nearly impossible, it means that there is a great deal of conference diversity in the year's biggest bowls. All three of those teams could potentially make the College Football Playoff next year if a similar situation occurs, and while some might argue that it would lead to the best battle for the national titles, others don't want to see teams from the same conference playing each other.
No matter what the College Football Playoff does, there are always going to be teams complaining that they deserve to be involved. Expanding the national title pool by two teams will definitely help to a certain degree, but the fifth team that gets left out will have an argument as well.
All of those teams can make a legitimate case that they should have a chance to play for the national title, but someone is bound to have their feelings hurt. Even if the College Football Playoff is expanded to eight teams down the line, that ninth team will have a gripe.
In addition to that, now that a panel is in place to determine the participants, personal bias can come into play, and that will create even more problems. One thing that really stands out about the College Football Playoff is that the big bowl games will be integrated into the playoff on a rotating basis.
According to CollegeFootballPlayoff. Most of those bowls always feel important, but the College Football Playoff will unquestionably take it to a different level. Also, the addition of the Cotton Bowl and Chick-fil-A Bowl ensures that two more bowls will reach elite status. The Cotton Bowl was once considered to be one of the biggest around, but its importance has waned in recent years.
Its inclusion in the College Football Playoff rotation will unquestionably revitalize it, though. Now these bowls will carry a win-or-go-home stipulation in some cases, and that is only going to increase interest and viewership. College football fans have the utmost respect for tradition. The sport was built upon it, and it's important to keep it alive.
With that said, tradition has a way of making things stale at times. That can be said for the marquee bowl matchups under the BCS system. All of the top bowls are attached to at least one conference, and that limits what can be done. For example, the Rose Bowl almost always has to be Pac vs. Big Ten, so there is definitely a lack of variety. That won't be an issue when it comes to the College Football Playoff since the best will play against the best regardless of conference affiliation.
That may not be appealing to purists, but the vast majority of college football fans will welcome the change. It's time to build a new tradition when it comes to bowl games, and the College Football Playoff will allow that to happen. Follow MikeChiari on Twitter. Enjoy our content? Join our newsletter to get the latest in sports news delivered straight to your inbox! Your sports.
0コメント