Pharmaceutical dosage forms .Medical background .Product information .Market analysis .Competitors .Doctor specialtyMessage to drs .

Types of dosage forms:

The need for dosage forms:

1- Accurate dose.

2- Protection e.g. coated tablets .

3- Protection from gastric juice.

4- Masking taste and odor.

5- Placement of drugs within body tissues.

6- Sustained release medication.

7- Controlled release medication.

8- Optimal drug action.

9- Use of desired vehicle for insoluble drugs.

They are classified according to:

Route of administration Physical formOral SolidTopical SemisolidRectal liquidParenteralVaginalInhaledOphthalmicOtic

Types of dosage forms (Cont.):

Oral dosage forms:

1-Tablet:

A tablet is a hard, compressed medication in round, oval or square shape.

1-Tablet (Cont.)

A coating may be applied to:1- hide the taste of the tablet's components.

2- make the tablet smoother and easier to swallow .

3- make it more resistant to the environment.

4- extending its shelf life.

3-Effervescent tablet:

Effervescent tablets are uncoated tablets that generallycontain acid substances (citric and tartaric acids) andcarbonates or bicarbonates and which react rapidly inthe presence of water by releasing carbon dioxide.

-They are intended to be dissolved or dispersed in waterbefore use providing:

A- Very rapid tablet dispersion and dissolution.

B- pleasant tasting carbonated drink.

4- Chewable tablet:

- They are tablets that chewed prior to swallowing.

- They are designed for administration to children e.g. vitamin products.

5- Capsule:

A capsule is a medication in a gelatin container.

- Advantage: mask the unpleasant taste of its contents.

- The two main types of capsules are:

1- hard-shelled capsules, which are normally used for

dry, powdered ingredients,

2- soft-shelled capsules, primarily used for oils and for active

ingredients that are dissolved or suspended in oil.

Soft gelatin capsuleHard gelatin capsule

6- Lozenge:

-It is a solid preparation consisting of sugar and gum, the

latter giving strength and cohesiveness to the lozenge

and facilitating slow release of the medicament.

11/20

Oral tablets Orodisperible tablets

They are to be swallowed through GIT passage or GIT entry .they pass through liver circulation and metabolism process .

They are to be placed under the

tongue and produce immediate

systemic effect by enabling the

drug absorbed directly through

mucosal lining of the mouth

beneath the tongue.

Absorption through GIT (Stomach –Duodenum –Intestine ) and pass through portal circulation (First pass effect )

Absorption through oral cavity

avoids first-pass metabolism

(does not pass through portal

circulation & less metabolism )

Oral tablets Sublingual tablets-The tablet are small & Big .-Durable taste or no-The tablet not dissolve quickly

and take from 1-3 hrs to be absorbed completely .

-The tablets are small & flat,

-compressed lightly to keep them

soft.

-The tablet dissolve quickly

allowing the Active ingredient to

be absorbed quickly.

It ‘s designed to dissolve in GIT organs . (Stomach - Duodenum – Intestine )

It’s designed to dissolve in small

quantity of saliva.

-Slow on set of action .

-Slow absorption

-Decrease B.A.

-More side effects

-Not Suitable in disease like

nausea & V.

-Requires water

-Fast onset of action (the fastest )

-Rapid absorption

-Increase B.A.

-Reduction in side effects

-Suitable in disease like Migraine

also N. & V.

-Not need for water

Mechanism of transportation (sublingual )

Highly vascular mucosal lining

Sublingual capillaries and veins

Jugular veins

Superior Vena cava

Arterial Circulation

14/20

PharmaMix

Pharmaceutical Promotion & Marketing

presents

Oro-Dispersible tablets

The Fast Powerful Migraine Relief

Frontal : responsible for

personality characteristics

Parietal :controls PAIN

Occipital : involved with vision

Temporal : responsible for

memory, smell & speech

4 lobes of Brain

Brain Anatomy and Parts of the Brain

The brain is made up of

three major segments -

forebrain, midbrain and

hindbrain.

Each segment consists of

different parts.

1- ForebrainThe forebrain is the largest segment of the

brain located in the upper most part of the brain , It consists

A - Cerebrum

B - Thalamus

C - Hypothalamus

A- Cerebrum :

- The cerebrum or the cortex is the largest part of the brain

( thinking & remembering) .

- Separated into two hemispheres right & left by

a deep longitudinal groove called the cerebral fissure.

- The right hemisphere controls the left side of the body and

vice versa..

B- Thalamus

Both sensory & motor behaviors.

C- Hypothalamus

Hormonal Regulation

The upper section of the

brainstem which is the

lower part of the brain

adjoining the spinal cord

2- Midbrain

3- Hindbrain- Located at the upper part of

the spinal cord .

- Responsible for the vital functions :

Respiration & heart beat.

consists of

Cerebellum, Pons ,Medulla oblongata

Cerebellum-Cerebellum contains more than 50% of the total neurons.

- Controls & regulates coordination of movements.

Pons & medullaare parts of the brainstem

that connects the brain with spinal cord.

Pons

- Contain control centers of face & eye movements.

- origins of 5th, 6th, 7th and 8th Cranial nerves.

Medulla

- Contains control centers of heart & lungs.

- The cranial nerves 9th, 10th, 11th, and 12th

The meninges

Are 3 membranous envelopes:

1- The pia mater,

2- The arachnoids

3- Dura mater

that surround the brain and spinal cord.

Migraine

Migraine headache is a complex, recurrent headache disorder .

In the United States, more than 30 million people have 1 or more

migraine headaches per year.

Approximately 75% of all persons who experience migraines

are women .

The term migraine is Greek word hemikrania.

The classic migraine episode is characterized by:

“unilateral head pain preceded by various visual, sensory,

motor symptoms, collectively known as an aura”.

The aura consists of visual manifestations such

as scotomas, photophobia . (e.g., bright zigzag lines)

However, migraine headaches may be unilateral or

bilateral and may occur with or without an aura.

In the current International Headache Society (IHS)

categorization, the headache previously described as

classic migraine is now known as migraine with aura,

and that described as common migraine is now

termed migraine without aura.

Migraines without aura are the most common,

accounting for more than 80% of all migraines.

Migraine Headache Classification :

“The International Headache Society (IHS)

• Migraine without aura, or common migraine

• Migraine with aura or classic migraine.

Pathophysiology

The mechanisms of migraine remain not completely understood.

Migraine is associated with a neuronal network excitability, with

activation and sensitization of

the trigeminovascular system.

Signs & symptoms

Migraines present with recurrent severe headache

associated with autonomic symptoms.

An aura only occurs in a small % of people. it is variable

Severity of the pain .

Duration of the headache.

Frequency of attacks

The prodrome The aura The pain The postdrome

which occurs

hours or days

before the

headache.

Incidence

40–60%

which immediately

precedes the

headache

Incidence

20–30%

also known as

headache phase,

usually in 1/2 of

the head

accompanied by

nausea, vomiting..

The effects of

migraine may

persist for some

days after the

main headache

has ended.

They appear

gradually over 5

to 20 minutes

generally last less

than 60 minutes.

It increases gradually

and lasts from

4 - 72 hours.

Symptoms include :

1-altered

mood, irritability, depr

ession or euphoria,

2-

fatigue, yawning, exces

sive sleepiness,

3-craving for certain

food (e.g. chocolate),

4-stiff ms (sp.in

neck), hot ears,

5- constipation or

diarrhea, increased

urination .

Symptoms include

1-photophobia

foggy vision ,

colored vision,

bright lines in

front of eyes,

2- sensation of pins

or numbness on

body .

3- vertigo, loss of

smelling power,

nausea/vomiting

Symptoms

include :

1- mood

changes,

depression,

tiredness,

2- loss of

appetite etc

• Symptoms include :

1- a sore feeling in

the area where the

migraine was, mood

changes .

• some report

impaired thinking

for a few days after

the headache has

passed.

The pt. may feel

gastrointestinal

symptoms, mood

and weakness.

The prodrome The aura The pain The postdrome

Migraine Headache Cause:

The cause of migraines is unknown.

Migraine Headache Triggers:

A trigger is any stimulus that initiates an episode of migraine.

A migraine episode can be precipitated by exposure or withdrawal of triggers

• Emotions and stress: Emotional disturbances like grief, anger, stressful

life, mental over exertion can precipitate an attack.

• Alcohol : Intake of alcohol or withdrawal of alcohol might trigger an attack.

• Environmental factors (e.g., weather, attitude, time zone changes)

Migraine Headache Triggers:

• Foods that contain caffeine

• coffee, chocolate),

• monosodium glutamate (found in Chinese food),

• light aggravates headaches in some.

• Hormonal changes in women: Many women complain of headaches either

before or during menstrual periods while others have during pregnancy or

menopause.

• Hunger

• Lack of sleep

• Certain Medications

• Perfume & other strong odors

At least 2 of the following features:Plus at least 1 of the following

features:

Unilateral pain Nausea or vomiting

Throbbing pain Photophobia & phonophobia

Aggravation by movement

Moderate or severe intensity

Simplified Diagnostic Criteria for Migraine

The International Headache Society elaborated diagnostic criteria for migraine.

These are as follows:

• Repeated attacks of headache lasting 4–72 h in pts with a normal physical

examination (no other reasonable cause for the headache) and:

neuronal network excitability

activation and sensitization of the trigeminovascular system.

Trigeminal nerves with their cell bodies in the trigeminal ganglion transmit sensory impulse caused by distension of the blood vessels of the Dura and meninges. The peripheral terminals of these neurons also release potent neuropeptide vasodilators,

Sensory impulse from the trigeminal nerves is carried from the trigeminal ganglia to the brainstem trigeminal nucleus caudalis (TNC),

higher brain centers are activated in the thalamus & cerebral cortex, resulting in the perception of headache pain

1 .Trigeminal nerves with their cell bodies in the

trigeminal ganglion transmit noxious sensory input caused by

distension of the blood vessels of the dura and meninges.

The peripheral terminals of these neurons also release potent

neuropeptide vasodilators, Substance P and Calcitonin Gene Related

Peptide (CGRP), causing dilation of dural blood vessels

2 .Sensory input from the trigeminal nerves is conveyed

from the trigeminal ganglia to the brainstem trigeminal

nucleus caudalis (TNC).

3. From the TNC, higher brain centers are activated in

the thalamus and cerebral cortex, resulting in the

perception of headache pain.

The serotonin receptor (5-hydroxytryptamine [5-HT]) is

believed to be the most important receptor in the headache

pathway.

Stimulation of the trigeminal nerve releases substance P (SP),

calcitonin gene-related peptide (CGRP), and neurokinin A (NKA).

These substances produce neurogenic inflammation that then

interacts with the blood vessel wall, producing dilatation, plasma

extravasation, and sterile inflammation.

Plasma extravasation is blocked by ergots, sumatriptan,

the newer 5-HT1B/D agonists, indomethacin,

acetylsalicylic acid, gamma amino butyric acid (GABA)

agonists such as valproic acid and benzodiazepines

These findings suggest that sumatriptan and selective

5-HT1 agonists decrease headache by abolishing

neuropeptide release in the periphery and blocking

neurotransmission by acting on second-order

neurons in the trigeminal-cervical complex.

Management of Migraine :

Management

There are three main aspects of treatment:

1. Trigger avoidance.

2. Acute symptomatic control.

3. And pharmacological prevention.

Medications are more effective if used earlier in an

attack.

Trigger avoidance

A headache diary may help determine what triggers a persons migraines

and therefore help them avoid these triggers. A trigger may occur up to 24

hours prior to the onset of symptoms. The majority of migraines are not

however caused by triggers.

Migraine treatment

Pharmacologic agents used for the treatment of migraine can be

classified as abortive (i.e., for alleviating the acute phase) or

prophylactic (i.e., preventive).

Abortive medications include the following:

1. Selective serotonin receptor (5-HT1) agonists (triptans)

2. Ergot alkaloids

3. Analgesics

4. Non-steroidal anti-inflammatory drugs (NSAIDs)

5. Combination products

6. Ant-emetics

Prophylactic medications include the

following:

• Antiepileptic drugs

• Beta-blockers

• Tricyclic antidepressants

• Calcium channel blockers

• NSAIDs

Product Information

Solpadol 5mg

Oro- Dispersible Tablet

DESCRIPTION

Solpadol Orally Disintegrating Tablets contain

zolmitriptan, which is a selective 5-

hydroxytryptamine 1B/1D (5-HT1B/1D) receptor agonist.

Mechanism of Action

Migraine headache symptoms are suggested to be due to local cranial

vasodilatation &/or to the release of sensory neuropeptide through nerve

endings in the trigeminal system.

Zolmitriptan (and its N-desmethyl metabolite) has high affinity to 5-HT1D

and 5-HT1B receptor & low affinity for 5-HT1A receptors.

Zolmitriptan has an agonist effect at the 5-HT1D/1B receptor on intracranial

blood vessels and sensory nerves of the trigeminal system, causing local

cranial v.c & inhib. of pro-inflammatory neuropeptide release.

Pharmacokinetics:

Absorption:

• Zolmitriptan display linear pharmacokinetics after oral

administration.

• Food has no significant effect on the bioavailability of

zolmitriptan.

• No accumulation occurred on multiple dosing.

Distribution:

The mean absolute bioavailability is approximately 40%. Plasma

protein binding is 25%

Metabolism:

• Zolmitriptan is converted to an active

N-desmethyl metabolite .

Elimination:

• Total elimination in urine and feaces are 65% and 30%

respectively.

• About 8% of the dose was recovered in the urine as

unchanged zolmitriptan.

SPECIAL POPULATIONS:

Age: Zolmitriptan pharmacokinetics in healthy elderly non-migraineur

volunteers (age 65−76 yrs) were similar to those in younger non-migraineur

volunteers (age 18 - 39 yrs).

Gender: Mean plasma concentrations of zolmitriptan were

up to 1.5-fold higher in females than males.

Renal Impairment:

Severe renal impairment :Clearance was reduced by 25%

Moderate renal impairment :no significant change in clearance

Hepatic Impairment:

Zolmitriptan should be administered with caution in subjects with liver

disease, generally using doses less than 2.5 mg

Hypertensive Patients:

No differences in the pharmacokinetics of zolmitriptan or its effects on

blood pressure were seen in mild to moderate hypertensive

volunteers compared to normotensive controls.

DRUG INTERACTIONS:

• Fluoxetine, the pharmacokinetics of zolmitriptan were unaffected by

4 weeks of pretreatment of oral fluoxetine.

• MAO-A inhibitors (following one week of administration), lead to a

great increase in the conc. of zolmitriptan & its active metabolites.

But a selective MAO-B inhibitor has no effect on the pharmaco-

kinetics of zolmitriptan & its metabolite.

• Cimetidine half-life of zolmitriptan & its active metabolite were

approximately doubled following cimitidine administration.

• Oral contraceptives, plasma concentration of zolmitriptan were

generally higher in female taking oral contraceptives compared to

those not taking oral contraceptives, zolmitriptan mean Cmax is

increased and Tmax was delayed.

• Propranolol the Cmax of zolmitriptan increased 1.5 fold after one

week of dosing with propranolol .

• Acetaminophen has no effect on zolmitriptan but zolmitriptan

delays the time of maximum concentration in the blood of

acetaminophen by one hour.

• Metoclopramide, a single 10 mg dose of metoclopramide had no

effect on the pharmacokinetics of zolmitriptan or its metabolites.

INDICATIONS AND USAGE:

•Solpadol is indicated for the treatment of

acute migraine with or without aura in adults.

•It's not intended for the prophylactic therapy of

migraine

CONTRAINDICATIONS:

• Hypersensitivity to the active substances or to any of its excipients.

• Ischemic heart disease patients

• Uncontrolled hypertension.

• Not be given within 24 hours of treatment with another 5-ht agonist, or

an ergot-containing or ergot-type medication.

WARNING AND PRECAUTION:

-Solpadol should not be given to patients in whom unrecognized coronary

artery disease (CAD) is predicted by the presence of risk factors (e.g.

hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong

family history of CAD).

-Its recommended that patients who are intermittent long term users of

Solpadol and who have or acquire risk factors predictive of CAD, undergo

periodic interval cardiovascular evaluation as they continue to use

Solpadol.

SIDE EFFECTS:

Some patients may experience pain or tightness in the chest or throat, shortness

of breath, wheeziness, heart throbbing, swelling of eyelids, face, or lips, or a skin

rash may happens rarely.

Rare side effects: tingling, heat, drowsy, dizzy, tired, or sick.

PREGNANCY AND LACTATION:

This product is not to be used in pregnancy or lactation except when the

potential benefit justifies the potential risk.

DOSAGE AND ADMINISTRATION:

The recommended dose is 2.5 mg to 5 mg of Solpadol tablets for

treatment of acute migraines in adults.

If migraine returns, a second dose may be taken not less than 2 hours

after the first dose.

(The maximum dose of Solpadol in 24 hours is 10 mg).

OVERDOSAGE:

There is no experience with clinical overdose. Volunteers receiving single

50 mg oral doses of zolmitriptan commonly experienced sedation.

INSTRUCTIONS TO PATIENTS:Patient should be instructed not to remove the tablet from the

blister until just prior to dosing.

PACKING AND PRICE : A pack of 3 strips, each containing 2 tablets of 16 L.E.

STORAGE:Store at controlled room temperature not exceeding 30 Cº

.Protect from light and moisture and keep out of reach of

children.