Preparation And Evaluation the Extract from Herbal Source for Pathological Condition- Migraine

What are pathological conditions:

Pathological conditions refer to any disease, disorder, or abnormality that disrupts the normal functioning of tissues, organs, or systems within the body.

 These conditions arise from a variety of causes, including genetic mutations, infections, injuries, environmental factors, and degenerative processes. Pathological changes can affect the structure and function of cells and tissues, leading to symptoms and complications that may impair a person's quality of life.

Examples of pathological conditions include cancer, where cells grow uncontrollably; cardiovascular diseases, which disrupt the flow of blood; and autoimmune disorders, where the immune system mistakenly attacks healthy tissues.

Diagnosis and treatment depend on the specific condition and its underlying causes, with therapies aimed at managing symptoms, correcting dysfunction, or halting disease progression.

Pathological conditions can be classified into several types based on their causes, nature, and affected systems. Here are some major types:

1. Infectious Diseases: Caused by pathogens such as bacteria, viruses, fungi, or parasites. Examples include tuberculosis, HIV/AIDS, and malaria.
2. Genetic Disorders: Result from inherited mutations or genetic abnormalities, such as cystic fibrosis, sickle cell anemia , and down syndrome.
3. Autoimmune Diseases: Occur when the immune system mistakenly attacks healthy tissues. Conditions like rheumatoid arthritis, lupus, and multiple sclerosis fall under this category.
4. Degenerative Diseases: Characterized by the gradual deterioration of cells, tissues, or organs over time. Examples include Alzheimer's disease, Parkinson's disease, and osteoarthritis.
5. Neoplastic Diseases: Involve abnormal growths of cells, which may be benign or malignant (cancerous). Cancer, such as breast or lung cancer, is a major type of neoplastic disease.

What is Headache 

Headaches is a most common neurological condition and are often linked to disruptions in various parts of the brain, particularly in the cerebral cortex, which processes sensory information like pain, touch, and temperature. The brainstem, which regulates autonomic functions such as breathing and heartbeat, also plays a role in headache related symptoms. Additionally, changes in blood flow through the carotid arteries can impact the brain’s overall function, contributing to the onset of headaches. These connections highlight how different brain regions and their functions can influence the experience of headaches.

Fig.4 Types of Headaches

Pathological Condition -Migraine

What is Migraine :   

A migraine is a type of headache. It may occur with symptoms such as nausea, vomiting, or sensitivity to light and sound. In most people, a throbbing pain is felt only on one side of the head. Migraine is considered a neurological disorder, a type of pathological condition that affects the nervous system. It involves recurring headaches, often accompanied by symptoms like nausea, sensitivity to light and sound, and visual disturbances (aura). While the exact cause of migraines is not fully understood, they are thought to involve abnormal brain activity, including changes in blood flow and the release of certain chemicals. Migraines are often triggered by factors such as stress, hormonal changes, certain foods, and environmental stimuli. Neurological disorders, like migraines, are characterized by disruptions in normal brain and nerve function.

Causes:   

A migraine headache is caused by abnormal brain activity. This activity can be triggered by many things. But the exact chain of events remains unclear. Most medical experts believe the attack begins in the brain and involves nerve pathways and chemicals. The changes affect blood flow in the brain and surrounding tissues. Migraine headaches tend to first appear between the ages of 10 and 45. Sometimes, they begin earlier or later. Migraines may run in families. Migraines occur more often in women than men.

Some women, but not all, have fewer migraines when they are pregnant.  

Migraine attacks may be triggered by any of the following;

• Caffeine withdrawal  
• Changes in hormone levels during a woman's menstrual cycle or with the use of birth control pills  
• Changes in sleep patterns, such as not getting enough sleep  
• Drinking alcohol  
• Exercise or other physical stress  
• Loud noises or bright lights  
• Missed meals  
• Odors or perfumes  
• Smoking or exposure to smoke  
• Stress and anxiety   

Migraines can be classified into the following types:  

A migraine without aura: This subtype involves recurrent headache attacks lasting 4 to 72 hours. The pain is typically unilateral, pulsating in quality, moderate-to-severe in intensity, aggravated by physical activity, and associated with nausea, light (photophobia), and sound sensitivity (phonophobia).  

Migraine with aura: This subtype features recurrent, fully reversible attacks lasting minutes, typically presenting with 1 or more unilateral symptoms such as visual, sensory, speech and language, motor, brainstem, or retinal disturbances, usually followed by headache and other migraine symptoms.  

Chronic migraine: This is defined as a headache that occurs on 15 or more days in a month for more than 3 months, with migraine features present on at least 8 or more days in a month.

Probable migraine: This is a symptomatic migraine attack that lacks 1 of the features required to fulfill the criteria for 1 of the above and does not meet the criteria for another type of headache.  

Symptoms :   

There are two main types of migraines:   

1. Migraine with aura (classic migraine)   
2. Migraine without aura (common migraine)  

An aura is a group of nervous system (neurologic) symptoms. These symptoms are considered a warning sign that a migraine is coming. Most often, the vision is affected and can include any or all of the following:  

• Temporary blind spots or coloured spots  
• Blurred vision  
• Eye pain  
• Seeing stars, zigzag lines, or flashing lights  
• Tunnel vision (only able to see objects close to the center of the field of view)  

Other nervous system symptoms include yawning, difficulty concentrating, nausea , trouble finding the right words, dizziness, weakness, numbness, and tingling. Some of these symptoms are much less common with migraine headaches. If you have any of these symptoms, your provider will likely order tests to find the cause.    An aura often occurs 10 to 15 minutes before the headache, but can occur just a few minutes to 24 hours before. A headache does not always follow an aura.  

The headaches usually:  

• Start as a dull ache and get worse within minutes to hours  
• Are throbbing, pounding, or pulsating  
• Are worse on one side of the head with pain behind the eye or in the back of the head and neck  
• Last 4 to 72 hours  

Other symptoms that may occur with the headache include:  

• Chills  
• Increased urination  
• Fatigue  
• Loss of appetite  
• Nausea and vomiting  
• Sensitivity to light or sound  
• Sweating  

Symptoms may linger, even after the migraine goes away. This is called a migraine hangover.  

Symptoms can include: 

• Feeling mentally dull, like your thinking is not clear or sharp  
• Needing more sleep  
• Neck pain  

Exams and Tests:   

Your provider can diagnose migraine headache by asking about your symptoms and family history of migraines. A complete physical and neurological exam will be done to determine if your headaches are due to muscle tension, sinus problems, or a brain disorder.  There is no specific test to prove that your headache is actually a migraine. In most cases, no special tests are needed. Your provider may order a brain CT or MRI scan if you have never had one before. 

Treatment:   

There is no specific cure for migraine headaches. The goal is to treat your migraine symptoms right away and to prevent symptoms by avoiding or changing your triggers.    A key step is learning how to manage your migraines at home. A headache diary can help you identify your headache triggers. Then you and your provider can plan how to avoid these triggers.  

Lifestyle changes include:  

• Healthier sleep habits, such as getting enough sleep and going to bed at the same time each night • Healthier eating habits, including not skipping meals and avoiding your food triggers  
• Managing stress  
• Losing weight, if you're overweight  

If you have frequent migraines, your provider may prescribe medicine to reduce the number of attacks. You need to take the medicine every day for it to be effective. Medicines may include:  

• Antidepressants  
• Blood pressure medicines, such as beta blockers  
• Anti-seizure medicines  
• Calcitonin gene-related peptide (CGRP) agents  
• Botulinum toxin type A (Botox) injections may also help reduce migraine attacks if they occur more than 15 days a month.  

Some people find relief with minerals and vitamins. Check with your provider to see if riboflavin or magnesium is right for you. Some of these medicines may not be safe for a pregnant or breastfeeding woman to take.  

Mechanism Of Antimigraine Drug;

Oral Dissolving Film

• A fast-dissolving oral film is defined as “an ultra-thin film containing active ingredient that dissolves or disintegrates in the saliva at a remarkably fast rate, within few seconds without the aid of water or chewing’’.
• The fast release action is due to larger surface area and less thickness as compared to a tablet.
•  The saliva in the oral cavity wets the film as it consists of hydrophilic polymers and dissolves it rapidly.
•  Thus the drug is released into the saliva and is absorbed via the highly vascularized oro-mucosal tissues.

Developing formulations for children has been a challenging task.

•  Amongst other factors, palatability of formulations of pediatric oral medications is one of the most significant factors influencing compliance to therapeutic regimens.
• Although solid dosage forms are widely accepted by elders and adolescents, younger children tend to prefer liquid formulations that are easier to swallow.
•  Keeping the ease of administration and swallowing in mind, pharmaceutical research has led to the development of fast dissolving oral films (FDOF’S).
• Research and development in the oral drug delivery segment has led to transition of dosage forms from simple conventional tablets/capsules to modified release tablets or capsules to oral disintegrating tablet (ODT) to wafer to the recent development of fast dissolving oral films.
•  Basically the FDOF’S can be considered as an ultra-thin strip of postage stamp size with an active agent or active pharmaceutical ingredient and other excipients.
• The advantages of convenience of dosing and portability of FDOF’S have led to wider acceptability of this dosage form by pediatric as well as geriatric population equally.
• The introduction of FDOF’S in market was accompanied by educating the mass about the proper way to administer the product like giving instructions ‘’do not swallow’’ or ‘’do not chew’.

The concept of oral dissolving film

1. This delivery system consists of a thin film.
2. After placing it on the top of the tongue, the film dissolves within seconds, promoting first pass metabolism as compared to tablet and other immediate release oral dosage forms, and may increase the bioavailability of the drug.
3. FDOF dissolves in the mouth like a cotton candy.
4. It is also called as oral wafers.
5. From the past few years the oral thin films are evolved in confection and oral care markets in the form of breath strips.
6. These are novel and widely accepted form by consumers for delivering vitamins and personal care products.
7. Today, FDOF’S are proven and accepted technology for the systemic delivery of APIs for over-the counter (OTC) medications and are in the early to mid development stages for prescription drugs.  
8. This has been attributed to the success of the breath freshener products by consumers such as Listerine pockets packs in the US consumer market.
9. Such systems use a variety of hydrophilic polymers to produce a 50-200 mm film.
10. The film is manufactured as a large sheet and then cut into individual dosage units for packaging in a range of pharmaceutically acceptable formats.

The Advantages of fast dissolving films

•  The film should be elegantly thin. 
• Films come in different sizes and shapes.
• It should not be obstructive in its nature.
• It should be able to cling to the mouth cavity without much difficulty;
• Disintegration without water and rapid medication release are two of the most notable features.
• Dosing convenience.
• There is no requirement for water to be used.
• There's no risk of choking on the food.
• Masking the taste
• An increase in the stability of the product.
• Patient compliance is improved.
• With a reduced first-pass hepatic effect, the drug enters the systemic circulatory system.

Salient features of fast dissolving oral films

• Available as thin, elegant films that are easy to handle and administer.
• Ease of administration even to bedridden and psychiatric patients.
• Good stability and solubility in water and saliva.
• The formulation of dissolvable films is customarily facilitated through aqueous polymer matrices than span a wide molecular weight range, thereby providing flexibility to achieve certain physical properties.
• Accurate dosa
• ge and pleasant in taste.

Disadvantages of ODF

• It is hygroscopic in nature so it is kept in dry place ..
• Packaging of film require special equipment and it is difficult to pack.
• High dose can not be incorporated into oral film.
• Eating and drinking may become restricted .
• Mouth dissolving film’s are moisture seneitive.

Classification of oral films

There are three types of oral films. They are:

1. Flash release/ Fast dissolving films (Placed on the tongue).
2. Mucoadhesive melts away films (Gingival or buccal region).
3. Mucoadhesive sustained release films (adhere to the buccal mucosa .

MATERIALS AND METHOD

Technologies used in the manufacture of mouth dissolving films:

1. Solvent casting

2. Semisolid casting

3. Hot melt extrusion

4. Solid dispersion extrusion

5. Rolling

Solvent Casting Method

In this method, the water soluble polymers are dissolved in suitable solvent and the drug along with other excipients is dissolved in suitable solvent. Then both solutions are mixed and stirred and finally casted into the petri plate and dried.

ADVANTAGES

• Greater uniformity of thickness and great clarity than extrusion.
• Films have fine gloss and freedom from defect such a die lines.
• Films have more flexibility and better physical properties.

DISADVANTAGES

• The polymer must be soluble in a volatile solvent or water.
• The stable solution with reasonable minimum solid content and viscosity should be formed.

Difference Between Oral Fast Dissolving Film and Oral Fast Dissolving Tablet

Treating An Attack   

Hydration with fluids is often helpful, with or without the use of medicines. Other medicines are taken at the first sign of a migraine attack. Over-the-counter (OTC) pain medicines, such as acetaminophen, naproxen, ibuprofen, or aspirin are often helpful when your migraine is mild.   

Synthetic drugs used in the treatment of migraine:

  A) Selective 5-HT agonist 

• • Sumatriptin 
  • Rizatriptan 
  • Naratritan 
  • Zolmitriptan

Ergot alkaloids 

• Ergotamine 
• Dihydroergotamine(DHE)

 C)Others 

• • Propranolol 
  • Amitriptine 
  • Valproic

Objectives

1) To formulate oral dissolving film by use of natural drug .

2)The aim of presented work is to formulate as well as evaluate the oral dissolving film that is –

• Safer to use .
• Minimum side effect .
• Better patient compliance .
• Easy to use.

3)Formula focus on to treat and prevent migraine problem .

4)Formulation prepared has no side effect beacause natural drug is use.

5)Formulation is evaluated for its physical and chemical parameter.

Plan Of Work

Master Formula

Formulation Of Oral Dissolving Film

? Herbal drugs used in treatment of migraine 

1. Ginger 
2. Lavender 
3. Peppermint 
4. Coriander 
5. Citron 

Advantages of herbal preparation over allopathy medicines 

1. Herbal preparations are made out of pure and organic ingredients.
2. They contain no synthetic additives or surfactants and are free of any side effect.
3. They are bio-degradable and eco-friendly.
4. Herbal products are more affordable than the synthetic one/
5. If chemical treatment is stopped, there may be chances that the problem may reoccur and can cause resistance if used for long priod.

Disadvantages Of Herbal Medicines 

Lack of standardization

Drug Profile

Synonyms : Zingiber, Zingiberis, Sunthi.

Family : Zingiberaceae 

Biological Source : Ginger consists of whole or cut, dried scrapped or unscrapped rhizomes of Zingiber officinale Roscoe, family Zingiberaceae. It contains not less than 0.8 per cent of total gingerols on dried basis 

Chemical constituents : ginger consists of volatile oil ( 1 - 4 %),starch (40 – 60 %) ,fat (10 %), fiber (5%), inorganic material (6%), residual moisture (10%), and acrid resinous matter (5-10%), ginger oil is constituted of monoterpene hydrocarbons , sesquiterpene hydrocarbons, oxygenated mono and sesqueterpenes and phenyl propanoids.

Sesquiterpenes hydrocarbon content of all types of ginger oil from different countries is found to be same and includes α- zingiberene , β- bisabolene, αfarnesene, β-sesquiphellandrene and α-curcumene.  Aroma and flavour are the main characters of ginger. Aroma is due to fragrant principles of volatile oil while the flavour, pungency and pharmacological action is exerted by phenolic ketones of oleo-resin. Various components of volatile oil like isometric terpenic aldehydes like geranial and citral, which cause the delicate and lemony aroma. Few sesquiterpene oil hydrocarbons ale believed to exert spicy note Phenolic ketones of oleo resin include gingerols like shogaols, zingerone, paradols, gingediols, hexahydrocurcumin and also omethyl ethers of these compounds. 

Uses: Ginger is used as a stomachic, an aromatic, a carminative, stimulant and flavouring agert. Ginger oil is used in mouth washes, ginger beverages and liquors, Ginger powder has been reported to be effective in motion sickness. It has been suggested tha adsorbent, aromatic and carminative properties of ginger on G. I. tract cause adsorption of toxins and acid enhanced gastric motility. These may have probably blocking effects of G. I. reactions and nausea. Z. officinale (Methanolic extract) has molluscicidal effects, possessing efficacy to control te parasitic infection viz. schistosomiasis. U.S. Food and Drug administration has included ginger s product that is generally regarded as safe (GRAS).

Methodology & Requirement

1. Collection of suitable references for study design. 
2. Selection of suitable extraction methods of selected ingredients. 
3. Selection and calibration of equipment required for drug study. 
4. Evaluation tests for the formulation.

Requirements:

Method of Extraction of Ginger: 

Isolation and standardization of gingerol from ginger  

1. Preparation of herbal extracts: The acquired plants were harvested and subjected to shade drying for 2-3 days and powdered using mixer grinder.
2. 10g of each drug was soaked in 100mla of ethanol
3. Stirred for 6-8hrs. at 970rpm a continuously using the mechanical stirrer
4. Subjected to Cold Maceration for about 72hrs. in refrigerator.
5. Later the macerated product was filtered and the filtrate was stored for its further usage

Identification:  

TLC method:  

Preparation of plate:  

Prepare a suspension of coating and spread a uniform layer of suspension. 0.25 to 0.30 mm thick on a flat glass plate of 20cm long. Dry in air and heat at 100 to 105°C and concentrate to 10ml.

Mobile phase: - Hexane: Diethyl ether (30:70v/v) 

Test solution: 1gm of coarsely powder substance with 25ml Methanol for 15 mins. Cool and filter. wash the residue with 10ml of methanol, combine all the filtrate and concentrate to 10ml. 

Reference solution: -0.5gm of powder with 5ml methanol for 15 mins. Cool and filter. Apply to the plate 10ul bands of 10mm by 2mm. 

ii. UV method Development: Calibrate curve of rhizome extract in methanol at wavelength of 281.40nm.

Evaluation of Extract

Alkaloid test:  

5g each of the ginger extracts and 5ml of honey was stirred with 5ml of 1% aqueous hydrochloric acid on a steam bath. Iml of the filtrate was treated with few drops of Draggendoff's reagent. Blue black turbidity serves as preliminary evidence of alkaloids. 

Saponins test:  

5g each of the extracts and 5ml of honey was shaken with distilled water in a test tube. Frothing which persists on warning was taken as preliminary evidence of the presence of saponins. 

Tannins test:  

5g each of the extracts and 5ml of honey was stirred with 100ml distilled water and filtered. Ferric chloride reagent was added to the filtrate. A blueblack or blue green precipitate determines the presence of tannins.

Flavonoids test:

5ml of diluted ammonia solution was added to aqueous filtrate of the test samples followed by the addition of concentrated sulphuric acid (H?SO?). A yellow coloration observation determines the presence of flavonoid.  

Terpenoid (Salkowski test):  

To 0.5 g of the extract, 2 ml of chloroform was added: Conc. Sulphuric acid (H?SO?) (3 ml) was carefully added to form a layer. A reddish brown coloration of the interface indicates the presence of terpenoid.

Trials And Errors