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.

Toronto’s Real Estate Market – The Sky is Not Falling!

I am sure you are just as tired as I am about hearing how terrible the current state of the real estate market is in Toronto, but is it really that bad?

No, the sky is not falling but there is no doubt that the Toronto real estate market has been affected by the US economic slowdown and because of this consumer confidence has also been affected … and some realtors have had to look for a "real job. "

The economic downturn in the states has no doubt had an impact on our economy. We are seeing fewer transactions occurring, (4,120 resale transactions in Feb '09 compared to 6,015 in Feb '08 according to TREB). Along with a reduction in the number of transactions that have occurred, average prices have also come down in comparison to the same time last year. According to TREB, in central Toronto the average price has gone from $ 404,202 (Jan, 2008) to $ 343,632 (Jan, 2009). Homes are also sitting on the market on average longer than the same time last year but what did we really expect? Did we really think last years wacky market of multiple offers and inflated prices would survive another year?

What does this real estate market mean to a Buyer or Seller in Toronto?

This is great news for buyers! This market is a blessing for first time buyers or those wanting home ownership but just could not afford it in the past. The declining average prices and the unbelievably low interest rates are a great combination! It's a Buyers market, so Buyers take advantage of this opportunity … it's a great time to buy! For sellers this type of market means pricing right and putting in extra effort to make sure your property shows at its potential. In the peak of the market, properties could sell the day they were put up for sale, now properties sit for longer but will still sell if priced right.

As we know, the real estate market is seasonal. As the spring market approaches all ready there is more activity in the city core than in the previous month. Just last week I was apart of two multiple offer situations in North York. Generally speaking the Toronto Real estate market tends to pick up in late spring and then begins its descend in July. The Canadian Mortgage and Housing Commission is forecasting that Toronto will see its 6th or 7th best year in history. They are hiring for 75,000 sales in 2009. The next few months will be a great indicator of the state of the Toronto Real estate market. I guess we'll just have to wait and see.

Learning How to Increase Vertical Leap – Important Information You Should Know

When athletes are learning how to increase vertical leap they are often bombarded with pages of information that results in a brain overload! When we are trying to learn something new often we go out trying to find out as much information as we possible can about the subject. In this case we would go out and try to find out as much as we can about how to increase your vertical jump. When it comes to learning how your body works when you jump and what muscle areas and energy you need to increase your ability to jump many athletes get confused from conflicting information. Don’t worry, I was at that stage once before as well where I was trying to sort through the pages and pages of information that I had found out about how to increase vertical leap. Oh, and don’t forget the shelves of books and reams of information scattered across my desk.

When it comes to working out one of the important factors is to have good nutrition. Did you know that when you are training your body it is using carbohydrates and proteins to fuel your body. But what happens once it runs out of these fuels? It starts to break down your muscles and use them as an energy source. This is why it is important to have a healthy, balanced and nutritional diet to prevent you from losing muscle power instead of gain it.

A common question I am asked about how to increase vertical jump is if hereditary factors plays a role. Yes some people are just naturally gifted jumpers because of their fast twitch muscle fiber to slow twitch muscle fiber ratio. The more fast twitch muscle fibers you have the more efficiently you are able to create force in a minimal amount of time. However, when it comes to this ratio you may not be able to change the fibers. However, you can change how quickly to recruit the generate power and also how much force they can generate. So realistically, if you think about hereditary factors, it does not play a major role in how high a person can jump.

Another factor that many athletes don’t know about when learning how to increase vertical jump is that there are different types of strength that affect how well you can recruit muscles to generate force to jump. When learning how to increase vertical jump we can split strength into 3 sub categories of absolute/limit strength, explosive strength and reactive strength. Absolute/limit strength is the foundation of all strength and is often the one that needs to be improved first before any of the other strengths. When we are learning how to increase vertical jump we need to focus on doing minimal reps with maximum effort because we are trying to train our explosive muscles, not our endurance muscles.

Branding Yourself For Success In Network Marketing

Branding oneself is critical if you are going to be prosperous in network marketing or MLM and more specifically if you wish to stay in this business for the longterm.

A great deal of people are actually asking me this question:

'I would like to enroll individuals into my company, how will branding myself as a leader help me to achieve this'?

People that ask this type of question bought to understand that enrolling individuals into your organization is a process and you can not neglect any steps within the process and anticipate to enroll individuals automatically.

If you decide to leverage the incredible power of the internet and market your business on the internet, you must realize that people do not know you so you will need to position your self as an MLM leader and that's where branding yourself becomes necessary.

When you are branding yourself on the internet, you are presenting yourself as an individual that has value to give and as someone who can provide solutions to other struggling network marketers.

A lot of people are in search of solutions and when they see that you have value to give, they will be naturally drawn to you and will turn out to be your lead which you can prospect and eventually sign up into your company.

If you consider large international companies, they continue to invest millions on marketing and advertising.

Why?

Mainly because they want to reinforce their brand in our minds.

In network advertising, you have to reinvigorate yourself in peoples' minds by branding yourself by means of giving value and supplying solutions to struggling network marketers.

Branding yourself is incredibly vital for these three reasons:

# 1 – People like to do business with people they like, know and trust

This is the main reason why we are taught in traditional network marketing to begin with family and friends.

However, when you have exhausted out your friends and family list, you must figure out how to tap into the market of individuals you do not know by branding yourself and standing out from all the other people pitching their businesses.

If you can invest some time into branding yourself as an MLM leader, you'll find it so much easier to attract leads to you and eventually sign them up into your company.

Always keep this in mind: people today join people, not companies.

# 2 – Regardless of what happens to your MLM company, you still have a business

What if your organization decides to close down for whatever reason, how would that affect your business?

If you have been focusing on marketing your company and not branding yourself, then you would be in a bad situation if your company does shut down for whatever reason.

However, if you have been branding yourself, it would not make a significant difference due to the fact that you would have built up a loyal following of individuals who want to work with you.

Therefore, if anything happened to your MLM company, a great percentage of the people on your list would wish to follow you wherever you go.

# 3 – Multiple income streams

In addition to your primary company, you are able to also make extra money on the internet from affiliate product sales.

Branding your self on the web will enable you to build a list of people that trust you so whenever you recommend a product that can help them, a good number of your list will purchase.

All because they already know you because of your brand and they would rather buy from you than someone they do not know.

So How Do You Begin Branding Yourself?

There are a variety of ways that can start to brand yourself on the web.

Blogging and article marketing and advertising are great ways to give value and brand yourself .

You can also cut videos on topics that will help your target audience.

Social media especially Facebook and twitter are also superb ways to brand yourself and develop your online presence.