6-Bench to bedside 1

what do FDA regulations on dietary supplements fo

allow manufacturers to sell botanical products without first proving they are effective

what should you watch for in supplement literature

Nitrogen within a structure

what to watch for in supplements when Nitrogen is there

pyrrolizidine alkaloids

Why should we know the process

to be expert on supplements and interactions

know correlation of chemical composition and pharmacological activity

have awareness on levels of quality available products and resources

Where should adverse effects be reported to

med watch

Does a product being natural mean it is safe?

no

What herbal studies have been studied

green tea, polyphenon E

crofelmer (fulyzak)

filsuvez

numbrino

Dietary supplement that has been studied

st johns wort

what is standarization

adjusting herbal drug preparation to a defined content of a constituent or a group of substances with known therapeutic activity by adding excipients or blending herbal drugs

what is standardization a pre requiesit for

consistent efficacy

What are prerequesties for consistent efficacy

measured designed to ensure consistency

adjust herbal to a defined ranged of therapeutically active components

what is double adjustment

adjustment of an herbal drug preparation to a fixed content of more than one therapeutically active constituent

What are the types of standardization extract

crude extract of a single botanical (one solvent)

crude extract of single botanical (more than one solvent)

combination extracts of two or more botanicals one solvent)

combination extracts of two or more botanicals more than one solvent)

quanitified extract

What does standardizing to ensure consistency comprise

• the herbal drug

• the extract solvent

• the manufacturing process

• in process control

• herbal drug preparation

what happens to extracts when standardized

adjusted to narrow tolerance to give content of constituents with known therapeutic activy or to a maker

how is adjustment carried out in extracts

with inert excipients or by blending batchers with a higher or lower content of therapeutically active constituents

what does adjustment with inert excipients lead to in extracts

a variable amount of native herbal drug prep or native extract

What are standardized extracts characterized by

specification and the ratio of drug to the native extractive (dernative) in its natural range

What must be known for adjustment of an herbal drug preparation to a defined range of therapeutically active constituents

active constituents must be known

herbal preps have to be ajusted with inert or blended

active constituents ensured

when can adjustments be restricted

to constituents showing strong activity and a narrow therapeutic range

what is the variability of defined range of constituents

+5%

Formula for adjustment with inert standardization

M1*C1=M2*C2

1= native
2- adjusted

How to find mass of adjustment material added

Subtract the final mass and the M1

Double adjustment what is fixed

native extract and theraputically active constituent

whats the advantage of double adjustment

consistance for both native extract and group of constituents

what is a downside to DERnative

only possible by blending batches or extracts, unrealistic for large scale

Double adjustment disadvantages

batches of good and bad quality are mixed

risk that suitable batches are not available

variability

physical parameter optimization is hard

What varies with double adjustment disadvantage wise

spectrum of concomitant constituents

physical characteristics batch to batch

What needs to be accounted for with extracts when adjusted to a defined range of active constituents

variability

should you tolerate adjusted to a defined range of inert constituents

no

can you tolerate adjustment of extracts with a defined range of active constituents by blending different batches

yes

quanitfied extracts

adjusted to a defined realistic rage of constituents that have a clinical or pharmacological effect

how are quantified extracts adjusted

blended batches of same specification on basis of a constant amt of native herb

example of a quantified extract

ginko

advantgaes of mixed extract

simple and economic way to manufacture

disadvantgae to mixed extracts

limited ability to extract constituents of interest

extraction rate and yeild of matter

increased analytical problems

fingerprint chromatograms needed to find origin of constituents

What are markers

factors in active constituents and markers variability

What factors cause variability in active constituents and markers in herbal products?

• Natural variation in plant constituents (can exceed 40%)

• Solubility and extraction rate

• Amount of extractable matter

What are markers in herbal products, and what is their purpose?

Chemically defined constituents that do NOT contribute to therapeutic activity.

Used for analytical purposes only (such as quality testing).

Marker catagories

charachteristic for the genus or family

occur ubiquitously in plants

What are markers characteristic of a specific plant genus or family used for?

• Identification and assay

• Batch-to-batch quality control

What are markers that occur ubiquitously in plants used for?

• Quantification only (batch-to-batch control)

• Do NOT provide information about the quality of the herbal preparation

marker eligibility

specific for respective test

selective determination among other constituents

stability

availability

can serve as analytical control during manufacture

How is a mixed extract made by extracting herbs together

1. Combine herbal drugs 1, 2, and 3.

2. Extract them together using an extraction solvent.

3. Obtain a mixed eluate → mixed-spissum extract → mixed extract.

How is a mixture of extracts made by extracting herbs separately?

1. Extract each herbal drug separately.

2. Obtain three individual extracts.

3. Combine the finished extracts into one mixture.

What are markers used for in the analytical control of herbal products?

1. Identification and purity testing

2. Batch-to-batch control

3. Determining extraction rate

4. Validating manufacturing conditions

   1. Stability testing

When can markers be used for stability testing, and what do they help demonstrate?

• When active constituents are unknown

• Help demonstrate batch-to-batch conformity (consistency between batches)

How are herbal preparations standardized when their active constituents are unknown?

By controlling the production process and quality control measures to ensure consistent, reproducible quality.

What parameters ensure reproducible quality in herbal preparations?

1. Detailed specifications of the herbal drug

2. Exact extraction solvent (type and concentration)

3. Optimized and validated manufacturing process

4. Consistent amounts of herbal preparation and inert excipients

What is foreign organic matter testing used for?

Detecting unwanted organic material in an herbal sample.

How is total ash determined?

• Use 2–4 g of air-dried sample.

• Heat at 675 ± 25°C until free of carbon.

• Remaining residue = total ash.

How is acid-insoluble ash determined?

Ash + 25 mL of 3 N HCl → Heat → Weigh acid-insoluble residue.

How is water-soluble ash determined?

1. Ash + 25 mL water → Heat

2. Collect insoluble matter → Wash → Ignite → Weigh

3. Water-soluble ash = Total ash − Water-insoluble ash

Questions from FDA to consider about BDS

should i check with my PCP?

do i need to think about my total diet?

what are risks of BDS if not standardized

Pyrrolizidine toxicity

CNS toxicity