Manufacturing

Extraction Processing Research

Botanica's manufacturing research program has been in place since 1994. This research is now co-managed by Botanica BioScience and PRI. Botanica is evaluating each step of extraction and herbal processing for effects on the consistency and potency of the final products. Standardized levels of characterized components are being developed for key ingredients. The Company believes that the resulting proprietary manufacturing methods add substantial value to its ingredients.
Manufacturing research and development programs yielding highly technical herbal extraction and concentration methods have been established to ensure efficacy in research studies and to ensure that similar potencies are available to the consumer who subsequently purchases these products. Substantial technical advantage continues to be gained in this area. The results of these programs yield low cost, high quality standardized extracts of botanical ingredients. In addition, Botanica undertakes research to optimize fermentation and cultivation of a variety of medicinal mushrooms.

Below is an example of lab-based research on extraction processing using an orthogonal study design. This protocol helps identify optimum transfer-rates with experiences-based modifications for cost, reference materials and other practical considerations. Here is the detailed report of the lab scale results.

In the following extraction research protocol three factors have been comparatively evaluated in a double-extraction process:
1. Factor A evaluates three different solvent combinations.
2. Factor B evaluates three different ratios of solvent to raw material
3. Factor C evaluates three different time to completion for each of the two extraction processes

Using this method, a total of 9 tests are carried out as shown in the L9 statistical table below.

In each of the 9 tests, 50 g of identical herb raw materials were prepared. The quantity of dried extract and its phytochemical content as represented by partially active marker compounds are evaluated. Statistical analysis to determine significance of the results is then undertaken to complete this study process.

Manufacturing Methods Development

Establishing, monitoring and assuring manufacturing reproducibility is critical, considering natural variations in plants that may be encountered in response to genetic and environmental factors. The effects of steps in the manufacturing process, which can alter the level and ratios of known biologically active or characterizing components, are evaluated. These steps cover a variety of conditions and techniques, and may include:

• Preparation: Maceration, grinding or milling
• Extraction: Temperature, solvents, duration, and repetitions
• Purification: Pressure filtration or centrifugal separators
• Fluid Removal: Spray or heat convection and drying temperatures
• Fermentation Conditions: Species, medium, stir rates, temperature, and timing

Botanica's manufacturing research programs incorporate methods such as mass balance and high pressure liquid chromatography to evaluate changes in the levels of identified characterizing components at each stage of the above listed procedures. This allows Botanica and PRI to identify the optimal process from preparation of raw materials to the final stages of drying and blending.

Analytical Methods for Co-Active Compounds

Even in the most carefully studied medicinal herbs, a complete understanding of all active components and their relative importance in the plant's biological activity has not been clearly determined. In order to evaluate the level of a particular component, referred to as a characterizing or marker compound, reference standards of that component are developed, some of which are not commercially available. High pressure liquid chromatography is then used to compare the level of the marker compounds to the reference standards. Because Botanica quantifies key components and uses traditional organoleptic and microscopic assessments, the Company's single herbs and herbal formulations offer valuable assurance to Botanica's customers that their product delivers the potential health benefits characteristic to each plant ingredient.

Manufacturing Capacity

Botanica together with PRI has managed single orders as large as 25,000 kilos of extract material consisting of more than 20 different herbal ingredients and representing over 200 tons of raw material. Botanica also has a fully integrated small-scale extraction facility with which we can produce small batches of extract. This facility also assists us in transferring the scale of production from lab-based extraction research to large commercial sized batches.