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.

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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.

5 Deadly Financial Mistakes You Should Avoid Now To Keep Out Of Debt Later!

Every year more families are going to the brink of financial ruin because they never properly considered their financial future. For some, it's just to stressful or emotionally uncomfortable to think about and important financial decisions get put off indefinitely. For many, they do not know and were never taught some basic financial planning tips to keep them out of debt in the future. Here are five financial mistakes you should avoid now to keep your financial future bright:

5 Financial Mistakes To Avoid:

1. Buying on credit: Today's interest rates are fairly low, but this does not mean you should buy excessively on credit! Carrying a large balance on credit cards month to month is a recipe for disaster. Finance charges alone can slowly eat you up. Buying a car on credit ties up even more of your future earnings for debt repayment.

Just a few decades ago buying so much on credit was unheard of. Children were taught early on what a huge mistake this was. We all need to relearn this lesson and eliminate buying on credit to keep ourselves out of debt

2. Making financial decision based on emotion: When you are going through great stress or emotional turmoil you are most vulnerable to making disastrous financial financial decisions. It is when you are feeling some king of pressure that you are most likely to make silly decisions that get you into trouble later. Do not make a big money decision when you are emotionally vulnerable.

3. Not adequately insuring against catastrophic risk: Every year families are financially devastated because they are not protected against disaster. Loss of home and assets to fire and flood are very common events that a surprising number of people do not protect against with insurance. You should also protect against disaster common to your area. Earthquakes and tornadoes for example. Just as important is some kind of life insurance to protect your loved ones in case of death.

4. Falling for the slick salesmen pitch: They say a sucker is born every minute. And you can be sure there is a slick salesmen waiting to take advantage of every one of them! You should never enter into any financial decision based on salesmen pressure tactics or one-time offers. Great deals that can not wait for you to think on it or obtain a second opinion are often financial disasters waiting to happen.

5. Not planning out your financial future: For many people it is so much easier to put off the tough financial planning right now and get to it someday in the future. Well we know how that story goes. Years into the future many families are neck deep in debt with no relief in sight. And it could of all been avoided with some sensible planning. Talk to a financial planner today so you can be debt free tomorrow!

There you have it. Five important financial mistakes to avoid so you can be both debt and worry free in your future. No matter where you are at right now financially, it's not to late to get started. Make an appointment with a financial planner today and get your financial future properly planned out. It's one of the most important things you can do for your family and for yourself.

BlueHost Review – Web Hosting With BlueHost

BlueHost has been offering web hosting service since 1996. It is considered to be one of the earliest hosting companies. Until today, this company has managed to survive in this fiercely contested web hosting industry while many other companies come and go. This tells us that they are a company that is able to provide quality hosting service to their customers. This is the main reason why they are still strong and running in the hosting industry.

Equipped with first class equipment, BlueHost is a company that uses modern quad servers, mirrored backups, backup generators and 24/7 monitoring by their trained staffs. All of this is to ensure that their service remains at an optimum level. Their internet connection is also superb providing a 2GB per second bandwidth.

As for their packages, they have adapted to the simplicity of packages nowadays by offering a one price package. They are well-known for their ‘Platinum Pak’ plan that offers 1500GB of disk storage, 1500GB of bandwidth plus industry standard features for only $6.95 per month. Users will also have the ability to host unlimited amount of domains and sub-domains under one account.

Like many other hosting companies, BlueHost also provides the cPanel control panel. It is considered as the most popular control panel system nowadays. With cPanel, web administrators can easily navigate and configure their hosting account with ease. BlueHost also provides Fantastico that can allow users to install a number of software packages based on their needs. There are packages for blogs, forum, content management system, picture galleries, online surveys and so on. Fantastic is a great tool that many webmasters like and by providing it in their plans, BlueHost has added even more value to their packages. For more advanced users, they will have access to many scripting languages like PHP5, PERL5, Python, Ruby On Rails and CGI. So, it is great users from all sorts of level.

As for the reliability of the service, BlueHost claims that they are able to provide users with a 99.9% uptime. No users will be happy with all the features and tools without a good uptime. According to tests being done, the overall uptime that was monitored for a period of 3 months have shown that the uptime provided by them have achieve the 99.9% target. However, there was a small amount of downtime throughout the testing period but that amount is considered to be very small if we compare it with other hosting providers.

From the aspect of support, users will be able to obtain support through their online help centre. In it, there is a huge list of articles covering a range of subjects. Many users find solutions fast and easy by using the help centre. Alternatively, users can contact the support staff through the normal way by using wither phone, email or live chat room. They provide 24/7 support and this is great for their users as the support staff could be contacted anytime when he or she is facing a problem with their account.

In conclusion, BlueHost is a company that has a lot off experience and is definitely a reputable company because it has been around for such a long time. So, if you are looking for a hosting provider, you could consider BlueHost to be your choice.

Hydroponic Gardening – Managing Pests & Diseases

As with soil-based gardens, hydroponic plants require good pest and disease maintenance controls. Failure to do so creates the same results as with 'ordinary' gardens ie spindly or dead plants. Since the majority of hydroponic plants are fruits and vegetables, that means the plants are not worth eating.

However, managing the hydroponic garden is even trickier, since disease and pests have it much easier in this setting. Plants are continuously kept wet, either immersed in water ('true' hydroponics) or continuously sprayed (aeroponics) or in a permanently wet medium such as perlite or sand. Fortunately, as with soil-based gardens, there is an extensive array of available methods to manage the problem.

Using beneficial life forms is one popular way to control unwanted pests, including certain types of bacteria and fungi. These can help to control spider mites and other invaders by crowding them out, eating them or releasing compounds toxic to the pest. They're known as beneficial organizations because they do all that without damaging the plants themselves.

Different types of pesticides are available, too.

Pesticidal soaps have been in use for centuries and still provide effective and non-toxic ways to keep the pests down. One category called botanicals are compounds released by plants themselves that have been combined into an easy-to-use pest control method. Botanicals break down naturally from exposure to air and water and are brilliant because they leave no harmful chemicals behind.

Neem oil can control over 400 different types of pest that typically invade gardens, including hydroponic ones. A simple spray to the leaves can often eliminate common pests. The bugs absorb the oil, which limits their ability to reproduce, leading to a lower population.

For more serious infestations, many commercial pesticides continue to work well.

White flies, aphids, mites and other pests can be a problem in hydroponic settings, just as in soil-based gardens. Powdery mildew is common. In fact, because of the continuous moisture bugs and pests have a 'friendly' environment. Making it 'unfriendly' is straightforward enough, using fungi and organicides. Sulfur-based compounds can help control white flies, mealy bugs, thrips and more.

Pyrethrum continues to be a safe and effective means of control. Although it sounds man made it is actually derived from flowers. This class of natural compounds released by plants are extracted and used in many commercial insecticides. Dosage is low, so the compound is very safe when used correctly (always read the label). Azatrol is a broad spectrum insecticide that provides another easy control method over most common pests.

Hydroponic gardeners have to exercise additional care when using any disease or pest control method, though. Since no soil is present to hold on to the roots, it's easier to damage a plant when manipulating the leaves and stems. That means that if you pick off mites by hand – an effective method for low-number infestations – it's important to exercise extra care.

Since moisture is present, mildew and other fungi are more common in hydroponic gardens. Keeping leaves dry and just the roots wet will help. Any insecticide sprayed on to your plants or vegetable should be allowed to dry under the grow lights. For aeroponically grown plants, for example, that may require a temporary relocation of the indoor garden.