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.

Helping Your ADD/HD Child

A number of factors need to be considered when you are told that your child is ADD/HD. The first thing you want to do is to understand all you can about ADD/HD. You also want to sit down and list what it means for your child, as a unique individual being, to be ADD/HD. Remember that this diagnosis is observational in nature.

If your child is ADD/HD, then your child was born ADD/HD. What has happened that has made it need to be labeled now? What were the stops along way that led from high energy, curious, creative and bright to disabled? Start a journal about your child, ask for observations, especially from the people who are around your child when you are not.

Ask yourself and other key people in your child’s life questions like: Are there times of day, days of the weeks, or certain situations which seem to trigger the child? Keep a food log and keep track as much as possible of what your child is eating. Are their certain foods that cause spikes and crashes? Or certain foods that lead to acting out or melting down? How about certain situations or people? Did the child have a year at school, or experience at camp where their behavior seemed to go to unmanageable? Were there major shifts in your child’s world such as living situations, acquiring or loss of a close friend or family member?

Talk with your child and have them tell you as much about their days as possible and compare it with what other people experienced of them that day. See where they may be making incorrect assumptions or did not understand the larger picture of what was going on in a certain situation.

Keep in mind that all very bright children have a great deal going on in their head and are impatient to learn, to understand, and will disconnect when bored.

If teachers or other people are strongly pushing the idea that your child is ADD/HD, ask them to be as specific as possible as to why. In order to gain a better understanding of what is going on, enlist them in getting the answers to the questions you are keeping track of. Also, ask what they think the solutions are if your child is ADD/HD. If they want to move to a drug based solution, make sure you are clear if there are benefits for them to have your child drugged and easier to manage.

Maybe your child is gifted with ADD/HD, so what you want to stay clear on is: When did that gift become an unmanageable problem, and will medication solve problems or mask them? First, remember that many factors are going on in your child’s life which could lead to a request for an official diagnosis and a recommendation of medication, and that in medicating, those factors will easily get lost because the medication seems to solve all the problems.

As you draw the picture of your child and your child’s relationship with an ADD/HD diagnosis, start shifting things and see how they shift the issues. Begin with diet, then look at what shifts can be made in the environment. Would smaller classrooms, more interactive educational methods and more challenging curriculum keep your child more focused and moving at a faster, more engaged pace that would both better serve your child’s learning, growth, and development, as well as, eliminate request for labeling or medication?

Keep the following things in mind if a diagnosis of ADD/HD is in the air:

Issues may be caused or exacerbated by diet, environmental, emotional, mental, even undetected physiological factors.

Second, if medicating, what are the short and long term side effects to the mental, emotional and physical well being of your child? Will this label serve them or hold them back?

Third, is the child being held responsible for situations where the failure is not theirs? Is their “failure” on account of an educational system that doesn’t know how to work with these children? Are teachers or other education or care providers ill equipped to provide what your child needs to fly and to flourish? I want to make it clear when I say “ill equipped,” it could be that the primary adults involved are ill suited, or that the situation which they are forced to function is incapable of providing the needed environment. But what I also want to make very clear here is that if we are medicating your child, or any child, because of the failure to properly provide the teachers, the classrooms, the resources needed, and that if they were all in place that a child would not have to be medicated, then medicating is morally reprehensible and we must examine our priorities in this country.

Or is the need to medicate them because we do not offer the support, education and resources to the family unit? Are we medicating them because the family can not or does not know what a bad diet is, or how to give these children the support they need? Or because the information is controlled by groups, institutions, and business who do not have the best interest of your child at hand? Do parents make the choice to medicate their child because of the one sided information that they are given, or are they coerced or manipulated into feeling that this is the only course of acting when in fact it is not? Is it made too easy in this chaotic, sped up, crazy world to convince yourself (to be convinced) that the quick fix is the right one. In other words, that a happy meal and pill is good parenting,

Lastly, dig past the top layer of information if you really want to know. Plenty of information is available on the internet. What you will often come across first is the controlled information. There are number of studies and evidence that on the surface support ADD/HD as a disability diagnosis and say that medication is the primary option. Large non-profit groups who serve this issue that are underwritten by the drug companies that manufacture it. But when you dig deeper, the evidence is not so clear or conclusive. The parts of the studies that question medicating as a viable option are often left out. We hear about the brain scans, but we only hear half a story. We don’t hear at all about the studies that have discovered alarming concerns about medicating these children because they are buried by the information provided by supporters of the pharmaceutical companies, and you have to dig deeper to find them.

Along the way you will also find any number of all natural one stop shopping wonders that claim to cure ADD/HD, and you should be just as wary of them. You need to have a whole child understanding, create whole child solutions and make sure that they represent the unique child that is yours. No quick fixes, no one size fits all approaches. And if everything I’ve said so far hasn’t made your head spin fast enough, I don’t see AD/HD as a disability, something one needs to get cured from or outgrow. It is part of an evolutionary process. These children and adults have a diff-ability, not a disability, they learn and process differently, they are not less able. In fact, they are often more able when they are set up to succeed, and not fail.

The question is: how do you want to best support your child? To fit in – or to be who they are, and be all they can be?

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.

Contemporary Kitchen Furniture – Points to Remember

When picking out contemporary kitchen furniture there are one or two things everyone should remember to avoid mistakes and an uneven finish to their new kitchen.

Firstly, do not assume you know exactly what contemporary means in relation to kitchen furniture. Do your homework and look at what's out there in terms of modern designs and ideas. You might be surprised at what constituents contemporary furniture and determined that it is not for you after all.

Always think about your kitchen when you're looking around showrooms. It's very easy to let a salesman tell you that particular furniture will look great in your contemporary kitchen, but if he has not seen your kitchen, how does he know? All kitchens are different in terms of light and space and will need different shapes and sizes of furniture to work effectively. Contemporary kitchen furniture is never one size fits all.

Sometimes the most important advice when it comes to picking out furniture for your kitchen is to remain consistent. If you go around picking out different bits and pieces without thinking about how they will go together, you can end up with a very disjointed and awkward looking kitchen.

Contemporary kitchen furniture needs to give off the impression of seamlessness and have clean lines in order to be authentic. This is not to say that your kitchen has a cold and sterile place to work in. You can add warmth and color to your kitchen by using the right materials and accessories.

These are just a few useful tips to help you ensure you get the contemporary kitchen that suits your needs.