Preformulation and Formulation Development

Optimizing Conformational Stability and Biological ActivityMaintenance of the native three dimensional conformation is critical for the long term stability and biological activity of biotherapeutics. Biophysical characterization techniques such as circular dichroism, differential scanning calorimetry, FTIR, dynamic light scattering, and fluorescence spectroscopy provide a mechanism to assess the conformational and thermodynamic stability of proteins under a range of formulation conditions. These tools allow development scientists to differentiate various various buffer, pH, ionic strength, and excipient conditions, and identify the conditions that confer the optimum environment for the therapeutic protein.

Utilizing Advanced Statistical Design for Preformulation Development Preformulation development includes statistical design of experiments, allowing simultaneous evaluation of multiple factors and evaluation of interactions between factors. It is crucial to use advanced biophysical characterization techniques to evaluate the conformational stability of large molecules in addition to traditional methods for evaluation of chemical stability.

A large molecule preformulation development program typically includes the following activities:
Evaluate the effect of pH, buffer type, and ionic strength on solubility.
Evaluate the effect of various excipients on improving solubility if necessary.
Evaluate effects of pH, buffer type, and excipients on conformational stability.
Evaluate the effect of pH, buffers, excipients and ionic strength on physical and chemical stability.
Utilize a statistical design approach to identify the optimal conditions for structural, physical and chemical stability.
Perform forced degradation to elucidate product degradation pathways and to demonstrate the stability-indicating capacity of the analytical methods.
Forced degradation studies typically include restricted oxidation, deamidation, aggregation (via agitation), and / or acid / base hydrolysis.
Evaluation of heat stress, photo stress, and freeze thaw are also performed.

Looking for information on Analytical Development and other related resources?

Formulation Development for Numerous Dosage FormsFormulation development includes dosage forms for parenteral, oral topical and inhalation administration, including liquids, gels, suspensions, emulsions and lyophilized powders. Formulation scientists are highly skilled in the development of the dosage forms most relevant to biotherapeutics, with particular expertise in lyophilization and development of stable liquid formulations for proteins. High concentration antibody formulation development for subcutaneous administration requires particular emphasis on viscosity and tonicity. Lyophilization cycle development is performed in the context of the unique thermodynamic properties of the API to deliver an efficient, scalable, transferable process resulting in optimum product stability and reconfiguration characteristics. Formulation development capabilities also include:

Effect of excipients on solubility, tonicity, and viscosity Evaluation of antioxidant and conservative compatibility Container-closure compatibility Long term and accelerated stability studies.

Advantages of Formulation Development Approach. This outlined approach to preformulation and formulation development result in significant savings to the client by eliminating the variables associated with suboptimal formulations. Preclinical development efforts in PK, PD, ADME and toxicology occur with confidence that additional uncontrollable variables from unstable formulations are not introduced into the study. This benefit extends far into clinical trials as well, where assessment of toxicity, dosage levels and efficiency are substantially influenced by an optimal formulation that preserves the three dimensional conformation of the therapeutic protein. By eliminating uncontrolled stability variables, the focus is placed solely on the therapeutic performance and clinical outcome.

Photography Backdrops And How To Select The Best One For You

You've studied all the different camera settings and by now you've learned all about the difference between shutter speed and f-stop. Thanks to your studies of lighting patterns, the difference between butterfly and split lighting is an obvious no brainer … Now, it's time to consider the backdrop.

In my experience, having over 6000 professional sessions under my belt, MOST people prefer to have a natural setting rather than a formal backdrop.

For example …

If you're shooting Indoors – possibilities may include placing your subjects on the floor around the fireplace, (always have a fire burning or it appears as nothing but a black hole in the final print), or they could be posed on and around their furniture in the living room, etc.

Outside portraits could be in their back yard, at the beach, a local park, etc. Anyplace that has meaning for THEM!

Most people just want a beautiful portrait that singles them out as individuals – rather than just another group posed in front of the same old pull down screen that everyone else uses.

Whenever possible, ALWAYS try for a location that has meaning for THEM …

However, if you must use a formal backup, here are a few suggestions …

First – buy a commercially available background stand to hold your backdrops. They do not cost much and for ease of use, stability, transportability etc. it's better than making your own.

For this discussion, I'm assuming you DO NOT own a professional portrait studio and are doing your sessions in your home (or your customer's home).

There are several types of backdrop materials:

Paper- Large rolls of paper come in most any color you can imagine. They can be purchased at many local camera stores and are relatively inexpensive.

Pros – They are readily available – are fairly inexpensive – come in most any color you can imagine. They can be used in a "sweep" so the model (s) can sit or stand on the paper and have it seamlessly up up behind them. Paper rolls come in two basic widths (around 4 feet and around 9 feet as I recall, I do not often use them).

Cons – The smaller size is not wide enough for much more than a head shot while the wider size is very heavy – difficult to transport – and most homes do not have enough "empty" space to sweep it without moving around the furniture. (People really do not like you redecorating for them!) The paper gets dirty, gets creased, tears and has to be constantly replaced. If there are animals in the session, the papery feel and crinkly sounds freak them out.

Painted Canvas – These can provide some truly stunning portraits. Many back suppliers create them and they can be ordered over the internet if you do not happen to be near a supplier.

Pros – Depending on the creator, they can be stunningly beautiful. There are thousands of colors and patterns available and if you have something unique in mind, you can have one created just for you, to match your exact specifications. They are very durable and will last years. They come in many sizes and can be used in a seamless sweep.

Cons – They are EXPENSIVE! EXPENSIVE! EXPENSIVE! Again, like paper, the wider ones are heavy, difficult work with and to transport. Like paper, size vs. living room furniture is a challenge.

Seamless paper and canvas backgrounds tend to be the province of professional studios – where they can be mounted on the walls and just folded down when needed.

They are really difficult to work with in the field.

I recommend that you go to the fabric store and get strips of material. As wide as is available and about 12 feet long. Getting some sort of material that either does not easily wrinkle, or where wrinkles will not matter is best.

Pros – Choose the type and colors you like, you can get any color, style and texture that suits your fancy. It can be hung bunched up (like theater curtains) behind the subject, or stretched flat if only one piece is needed. One piece can also be used as a seamless sweep.

You can use one piece or thirty – no matter how wide your back needs are, you can easily accommodate them.

It's easy to store and transport (just fold up the strips and put them in a box in the back seat of your car!) Material is very inexpensive compared to a painted canvas (which can run into the thousands of dollars) It's reusable so it works out to be cheaper than paper in the long run.

Use another piece of two for the flooring and since it's flexible, it can be flowed around furniture. Animals have no problem walking on it. (It's washable too!).

Cons – If you want multiple strips (and you do!), You may have difficulty finding enough of the same material. If you live near the garment district in a large city, they may have it. Otherwise you may have to have your local fabric store special order it for you.

These are the major background considerations and you should have no trouble finding the perfect backdrops for YOUR creative vision!

Successful Internet Marketing – You Must Have Web Hosting

What is a Web Host?

According to Wikipedia, a web host is “a type of Internet hosting service that allows individuals and organizations to make their own website accessible via the World Wide Web.” Web host services run the gamut from small, local companies who serve only a few clients, to large, multi-national companies who serve millions of clients. Regardless of their size, all hosting companies have one thing in common: They all provide you with space on the hard drives of their web servers where you upload your website’s files.

Free or Paid Hosting?

This debate rages on in the Internet marketing community. On the one hand you have those who advocate spending as little money upfront as possible until your business actually begins to make money online. This is the approach I recommend. On the other hand there are those who say you “get what you pay for” and free hosting is unreliable. I beg to differ. There are several very reliable free web hosting companies that have excellent uptime records. I use and recommend 000WebHost.com; their free hosting package boasts 99% uptime and they have all of the features that are necessary to set up a successful Internet marketing website or blog.

What Features Do I Need?

This is the question I am asked most frequently by newbie Internet marketers. My answer: It depends. If all you are going to do with your Internet marketing website is set up a few informational pages and a contact page, then you don’t much at all–any free web host will do. If you plan to set up a blog, multiple sales pages, newsletters, etc., you are going to need a full-featured hosting package. At minimum, you will need a package that includes plenty of storage space for your website files and graphics, sufficient data transfer volume to keep up with your traffic, and one or more email accounts.

For hosting your own blogging platform such as WordPress or Drupal, you will need PHP scripting language and MySQL database support. Also, many of the useful software tools and scripts that many Internet marketers use require PHP and MySQL to function. Most web hosts, including the one mentioned above, support this, so you shouldn’t have any problem in that department.

Finally, you will need to have access to your host’s server. All web hosts offer some type of graphic interface into your web space so you can configure and maintain your site, the most popular being cPanel. CPanel hosting is the de facto standard for most hosting services these days and there is plenty of information and training available free on the web.

Using Large Aperture Settings – Digital Photography Tips

If you want your photo to be as sharp as possible then you are going to need to learn some good information about how to use the aperture settings in your camera. Improper use of this in your camera can make for photos that are not as great as they possibly can be.

There are many different measurements in photography. The measurements are measurements mostly of light and the amount of time that the photo is exposed. The aperture is something that you really should try to understand. The aperture what controls the amount of light that is let into the camera.

In photography, light is critically important and controlling it correctly will make your photos much better. The aperture is measured in F-stops. There are different values ​​of aperture that can be large and small. A larger aperture will let more light into the camera for exposure. Because more light is let in you can expose the image faster and then use a faster shutter speed. This can really be useful when you are taking pictures of fast movement and need a fast shutter speed. Also, using a fast shutter speed will ensure you do not get the camera shake effect from your hands.

Another great tool that you can do with using a large F-Stop in your aperture is that it can make your image sharper. What the larger aperture will do is make the depth of field be much smaller. This will make whatever is out of the small depth of field be out of focus. This can make the background be very out of focus and the depth of field area will be in focus. Even if you have the object in focus slightly out of focus, since it is the only area of ​​the image that is in focus it'll look much more focused. Of course, you always want to make sure your photo is as focused as possible.

Using a smaller f-stop for your aperture will require the opposite of what the larger aperture does. Because the smaller aperture will make less light to expose the image, it will make you need to use a slower shutter speed to expose more light. What happens with a smaller opening as an aperture is that the light that is let in will be much more directed and then will make for much sharper images everywhere. A small aperture can make for very sharp images through the entire z axis. This will make the background in focus and the foreground in focus. This is great when taking landscape photos or photos of large fields like football fields where you want the entire picture in focus.