Pizotifen

Pizotifen

Pizotifen is a tricyclic compound having antiserotoninergic and antihistaminergic effects together with a weak anticholinergic action, but a little or no activity on kinins or their liberators. At low concentration Pizotifen may potentiate the actions of serotonin.

Mechanism of action

Pizotifen, like all triptans, is a serotonin agonist, which means it acts like serotonin. Serotonin, also known as 5-hydroxytriptamine (5-HT), is a neurotransmitter that regulates communication between nerve cells and the widening of blood vessels. It acts by activating proteins on nerve endings and blood vessels, called 5-HT receptors. Pizotifen also activates these receptors. Activation prevents the release of chemicals that mediate pain and narrows blood vessels, which reduces their leakiness.

Pharmacology

Pizotifen is characterized by its polyvalent inhibition effect on biogenic amines, such as serotonin, histamine and tryptamine. Pizotifen also possesses appetite stimulation properties.

Indication

Pizotifen is indicated for the prophylactic treatment of vascular headaches of migraine types such classical migraine, common migraine, and cluster headaches. It is also indicated in appetite loss of somatic or psychogenic organ in underweight patients as an adjuvant to treatment of the underlying condition, such as infection or parasitic diseases (including during convalescence), chronic diarrhea, anorexia nervosa, or depressive states in the elderly and mood disturbances in the elderly.

Contraindication

It is Contraindication in patient with `a history of hypersensitivity to any components of the product. Although its achlinergic activity it’s relatively weak, Pizotifen should be probably not be administered in the presence of narrow-angle glaucoma or prostate hypertrophy. Pizotifen should not be given in to children under 2 years of age.

Side effect

The most commonly occurring side effect are drowsiness and an increase in appetite, which may lead to increase in body weight. Other side effects such as dizziness, dry mouth nausea and constipation have been reported infrequency. In children, CNS stimulation may occur.

Pregnancy and lactation

As clinical data with Pizotifen in Pregnancy is very limited, although no ill effects have been reported. The drug should therefore only be given during pregnancy if the potential benefit to mother justifies the potential risk to the fetus. The safety of Pizotifen during lactation has not been established, so mother should avoid taking it when breast feeling.

Caution

Urinary retention, renal impairment, pregnancy and beast feeding should be taken in consideration. Drowsiness may affect the performance of skilled task (e.g. Dividing), effect of alcohol is enhances.

Precaution

Patient should be warned about the possibility of drowsiness and its significance in the driving of vehicle and the operation of machinery.

Drug interaction

Tolerance to alcohol may be lowered. Prolong the drowsiness that occurs as adverse effect of concurrently used tranquilizers, hypnotics and antidepressant. It should not be used in patients receiving monoamine oxidize inhibitors.

Dose and Administration

The recommended dose is as followings:

Adult: the initial dose is 1.5mg daily; this may be taken at bedtime as a single dose or in three divided dose. Dosage can be adjusted according to the individual patient requirement up to a maximum of 4.5mg daily. Up to 3mg may be given as a single daily dose.

Children: up to 1.5mg daily, usually as a divide dose. Use of 1.5mg at a time is not recommended, but up to 1mg can be given as a single daily dose at night. Children below two years of age should not be given Pizotifen.

Or, a directed by the registered physician.

Pharmaceuticals precaution

Store in a cool dry place protected from light. Keep out of reach of children.

Market competitors

Serial no.	Company Name	Brand name	Pack size	Unite per price	Selling price(per year)
01	Square	Migranil	Box containing 5×10 tablet Or 5×1 tablets in blister pack	3tk	TK. 22,751,915
02	Bexcimco	Avidro	Box containing 1×10 tablet Or 10×10 tablets in blister pack	3tk	TK. 5,938,344 tk
03	Drug International Ltd.	De-fen	Box containing 10×10 tablet Or 1×10 tablets in blister pack	2tk	TK. 6,580,221
04	Aristopharma Ltd.	Zofen	Box containing 10×10 tablet in blister pack	3tk	TK. 18,752,830
05	Opsonin Pharm	Pifen	Box containing 5×10 tablet in blister pack	2tk	TK. 2,503,136

SWOT analysis:

Seiral no.	Strength(Pizotifen)	Weakness(Rizatriptan)
01	It required low dose of Pizotifen as 1.5mg daily for acute treatment. So it active therapeutic effect at low dose	Rizatriptan required high dose as 5mg or 10mg daily for acute treatment it’s given low at high dose.
02	Children above 2 years it should be given	It is not recommended in children.
03	The bioavailability of this drug is 75%	The bioavailability of this drug is 45%
04	About 90% bound to plasma proteins. Peak plasma concentrations occur about 5 hr after a single oral dose.	About 5% bound to plasma proteins. Peak plasma concentrations occur about 10-15 hr after a single oral dose.

MICROMERITICS AND POWDER RHEOLOGY

MICROMERITICS AND POWDER RHEOLOGY

Importance of micromeritics in pharmacy

Size and size range of particles are very important in pharmacy.

1. Size and surface area of particles are related to physical, chemical and physiological properties of a drug.

2. The necessary flow properties of solid powders in tablet and capsule manufacture depends on the particle size, size distribution and size distribution.

3. Particle size of a drug affects the release from a dosage form administered orally, parenterally, rectally, and topically. Dissolution rate is faster from smaller particle size due to its high specific surface area.

4. Rate of sedimentation in suspension and rate of creaming in emulsion is faster with larger particles. Hence, to make a stable suspension or emulsion the particle size must be controlled.

5. For accurate determination of pore size of filters the size of particles are required.

6. Antigens are coated on adsorbent particles where the particle size is important for uniform dose calculation.

PARTICLE SIZE AND SIZE DISTRIBUTION

A powder sample is characterized by three things: (a) shape of the particles, (b) size of the particles and (c) size distribution of the particles. If the shape of a particle is perfectly spherical it is easy to express it by its diameter; but if it is not spherical then it becomes very difficult to express in diameter. Most of the pharmaceutical particles are not perfectly spherical.

If all the particles have same diameter then the powder sample is called a monodisperse system, but if all the particles are not of equal sizes then that powder sample is called polydisperse system. Most of the pharmaceutical powders and dispersion are polydisperse systems.

Average particle size

Suppose a powder sample is examined under microscope and the diameter of the particles are measured individually. The average diameter can be expressed in various ways. Edmundson has derived a general eqution for the average particle size (d_mean):

where n = number of particles in a certain size range

d = diameter of those particles

p = 1 stands for length, p = 2 stands for surface area and p = 3 stands for volume of the particle

If p > 0 (i.e. p is positive) then d_mean is arithmetic mean

If p = 0 then d_mean is geometric mean

If p <>mean is harmonic mean

f = frequency index [f has values of 0, 1, 2, 3 then the frequency distribution is expressed in number (0), length (1), surface (2) and volume or weight (3) of the particles, respectively.]

Let us take the following example:

Diameter (mm) (d)	Number (n)	nd	nd2	nd3	nd4
0.75 1.25 1.75 2.25 2.75 3.25 3.75	2 10 22 54 17 8 5	1.50 12.50 38.50 121.50 46.75 26.00 18.75	1.13 15.63 67.38 273.38 128.56 84.50 70.31	0.85 19.54 117.92 615.11 353.54 274.63 263.66	0.64 24.43 206.36 1384.00 972.24 892.55 988.73
	= 118	= 265.50	= 640.89	= 1645.25	= 4468.95

Statistical diameters:

	p	f	Type of mean	Size parameter	Frequency	Mean Diameter	Value of data obtained from the table	Comments
	1	0	Arithmetic	Length	Number	Length-Number mean, dln.	2.25	Rarely found in pharmaceutical powders
	2	0	Arithmetic	Surface	Number	Surface-number mean, dsn.	2.33	Refers to particles having average surface area.
	3	0	Arithmetic	Volume	Number	Volume-number mean, dvn.	2.41	Refers to particles having average weight
	2	1	Arithmetic	Surface	Length	Surface-length mean, dsl.2.41	2.41	No practical significance
	3	2	Arithmetic	Volume	Surface	Volume-Surface mean, dvs.	2.57	Inversely related to specific surface area* Important pharmaceutically

* Specific surface area =

Particle size distribution

When the number or weight of particles lying within a certain size range is plotted against the size range or mean particle size, a graph is obtained, that is called as frequency distribution curve.

Estimation of flow properties of a powder:

Two indicators of flow properties are there (i) Angle of repose (f) and (ii) Flow rate

Angle of repose

This is the maximum angle possible between the surface of a heap of powder and the horizontal plane.

It is an indicator of the frictional and cohesive forces in a loose powder.

Method-1:	Method-2	Method-3
Powder is released slowly through a funnel on a horizontal round surface. A heap will form. When the particles will glide over the heap the addition was stopped and the height (h) was measured. The diameter (D) of the round surface was known previously. Angle of repose, f =	A hollow cylinder is half-filled with the powder. One end of the cylinder is sealed with a transparent plate. The inside surface of the cylinder is lined with sand paper to reduce the slip of powder. The cylinder is rotated about its horizontal axis, until the powder surface cascades. The value of f is measured with a protractor.	A rectangular box is lined with sand paper. The box is filled with powder and tilted slowly until the powder begins to slide. The angle, f, is measured as the angle of repose.

Flow rate measurement:

The flow rate of granules (less cohesive materials) may be assessed by passing the powder through a circular orifice fitted in the base of a cylindrical container. The powder is taken in the container and released through the orifice on the pan of a balance. The weight of powder or granules falling per unit of time is recorded.

To improve the flow properties of granules a type of powders are used, they are called glidants. Examples of glidants are talc, corn starch etc.