The Stages Of Drug Development And Design For Herbal Medicine

Herbal drug production

Medicines are group into traditional and orthodox (western) medicines. Western medicines involve proper investigation of the activities of the drug, which is usually in a pure form in the dosage ranging from tablets to capsules etc. This is not the case with traditional drugs, which depends on the crude drug for activities. They are mostly in liquid forms.
Traditional medicines are more common in Africa and Asia with the western world using more of orthodox medicine. The success stories of many traditional medicines have made World Health Organization (W.H.O) to adopt guidelines in the incorporation of it into mainstream medicine.
The adoption of traditional medicines by who has led to the introduction of the methods used in orthodox medicine. Let us see how some of the popular drugs came about. The method here focuses on herbal drugs development but have similarity with synthetic products. For the herbal drugs developed by the methods, it can be called semi-synthetic drugs like hyoscine N butyl bromide.
Traditional drug discovery is divided into three stages viz: extraction, pre-clinical and clinical stages.
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Selection

The plant is chosen based on certain factors. The factors can be the use of the extracts of the plant by a group of person or literature review etc. The selection stage is usually very easy. I can decide to work on a plant today if I see where a person to treat a particular ailment used it. I will find out what is the constituent in the plant that worked for him. This is because plants have many compounds in them and it is only a few of them that are actively involved in the treatment. The right part to be collected is also noted, as some parts of plants are more potent than others e.g. the leaf of some plants are more potent than the root.

Collection

The plant is collected from the field. The collection is important as the wrong collection may produce a bad result. For example, some plants contain some compounds when the weather is cold or during harmattan, which may not be there when there is a change in weather. The right altitude, temperature, and time among another factor must be considered before the collection.
Identification: The plant must be checked by a professional to be certain it is the right plant. Professional can be a herbalist, a botanist etc.

Drying

The plant part is dried in a condition that will not destroy the active chemicals. Drying is normally done in a room that a lot of air does flow through. Drying under the sun may destroy many of the actives due to its rays. One more thing, drying can be avoided if the plant extract will be used immediately for the extraction. As we all know that this method is rear so it is best to dry and prepare yourself before rushing into processing.

Grinding

The finer the plant part, the more likely it is to get more of the active ingredient out of the plant parts. The plant part is ground using methods that do not produce heat.
Extraction: There are several extraction methods such as maceration, decoction, infusion, percolator etc. For maceration method, the ground plant extract is soaked in an alcohol solvent for some days. This will help bring out all the chemical compounds in the plant into the alcohol.

Filtering

The mixture is filtered using a filter paper. The shaft is discarded while the filtrate is condensed using a rotary evaporator. This removes the alcohol solvent leaving the just water and the extract. This is what they call galenic in honour of Claudius Galen.

Concentration

The galenic is concentrated to a very thick, smooth paste using controlled heat. The product is condensed with little water.

Identification Of Compounds

The extracts contain many different compounds and very few will be active. It is better to identify the compounds present and how to separate them from each other.
This is because some plants may contain a particular compound while others may not contain that compound. The method is very simple. First, try to find out the compounds that are present. This is done by studying the way the extracts react to certain compounds. The reactions are standard reactions that will give either a positive or negative result. E.g. test for saponins.

Separation

Knowing the compounds present will enable the scientist to design reaction that will separate the compounds. Different methods for different compounds. However, care must be taken to prevent damage to the actives. Separation techniques involve thin layer chromatography, column chromatography, high-performance liquid chromatography etc. These usually produce pure compounds without contamination. Take for example, in a thin layer chromatography, a plate is coated and activated. A solvent is prepared with such that it can travel up the plate when the plate is inserted. The extract is used to touch a particular spot on the plate. The plate is inserted into the solvent and the solvent starts moving up the plate. As it moves, it takes some of the compounds of the extract that are light with it while leaving the heavy ones behind. This way, you can get the different compounds in the extract.

Screening

The various chemicals are identified using techniques like infrared, ultra/violet radiation etc. The various chemicals are characterized such as the chemical structure, name, and all that.
For drugs gotten from chemicals during drug design and development, the agent is either synthesis, isolated or a compound is modified to another form that posses a better therapeutic effect.

Pre-Clinical Study

Biological Activity

The effectiveness of the compounds is carried out in the laboratory. The biological experiments to be carried out is determined by the expected outcome. For example, extracts that are believed to have antimicrobial effects will be tested for such activities. To do that, a petri dish containing a nutrient broth and the specific microorganism is treated with some few drops of the compound extract. The rate and zone of inhibition are observed. This can be done for all the separated compounds and the most effective are noted. Some test may even include combining two very effective compounds to see if they will have better synergistic effects than acting singly. If at the point of the test, the extracts were having a score less than products that are already in the market for treating similar conditions, it may be discarded as the drug regulatory body may not approve it. They may consider their stand anyway when the new product even though is less effective have higher safety profile which the one already in the market lacks.

Clinical Trials

This is the stage where most drugs meet their Waterloo. They may be ineffective against microbes and or dangerous to animal cells in animal models even after having a positive review at the laboratory. It is at this stage that one can tell if actually, the drug will stand clinical trial or not. The use of animals is introduced when laboratory works have been able to work out the likely effects on animal cells. The most preferred animal is the white albino rat. Their weight is noted and they are induced by the disease condition that the extract is expected to treat. The drug is introduced into their system most likely oral or intravenous or intramuscular. The dose is adjusted with weight. Up to 50 animals are used and the effects are monitored. This step takes years as it involves repetition to know how the drug is absorbed, distributed, metabolized, and excreted after it has been found to be effective against the disease. The best route of administration, best dosage form and all of that will be worked out at this stage. The safety, toxicity level, efficacy are noted. The effects of different race, gender, age is predicted from here.

Further Animal Studies

Higher animals that have their system almost similar to that of humans are used. They try to repeat the methods used in the rat models and try to be more observant. Varying the conditions to match similar conditions of planned use of the drug in human is closely monitored like when the animal is pregnant. The teratogenic effect is studied. Further proof as to best dosage form is analysed and all that.
Some studies carried out include:
Acute Studies: Effects of one or more doses administered over a period of 24 hours to determine the toxic dose.
Repeated Dose: Check for sub-acute, subchronic or chronic effects over a long duration.
Genetic Toxicity: To check the potential carcinogenic or mutagenic effect of the compound
Reproduction: The effect of the compound on mother and child before and after birth.
This time, a patent right is filed and an approval granted for further studies if all requirements have been fulfilled. If rejected, information will be given as to why.
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Clinical Studies

A group of few healthy human volunteers are used. They are given special doses as from information from previous studies. They are closely monitored. If successful, the volunteers are increased. This is followed by another set of volunteers. The last stage is the use of the drug in real life situation of an actual ill patient. If the product is effective as claimed, more studies of ill patients will continue. All the adverse drug effect to warn the public is taking note off.
Another patent right is filed with permission to mass-produce for the final phase: the post-market survey.
The extracts are made into series of probably suitable dosage forms with specifics as to how it should be taken with directions. Their expiry date, solubility, dissolution and all other tests that determine the stability of the dosage form is properly investigated before the extract now drug is released to the public for use. A series of the report obtained by medical experts in various medical feeds are obtained and analysed in the form of adverse drug reactions. It is called Post market survey.
A post-market survey is a system to monitor the actual activities of the drug in the general populace since the study was done with a relatively few number of people compare to the population that will use. This is where the actual drug effect is known.
With that, we have our drug product. This usually cost billions of naira from the start to the finish over a period of 10 years at most. This may be the reason why some drugs are very expensive and why most Nigerians are not into this kind of research. However, we hope years are coming when this stage will be made easier with the advance in technology.
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