D. Pharm - II Examination - 2016 (I) | PHARMACEUTICS

D. Pharm - II Examination - 2016 (I) | PHARMACEUTICS - II (THEORY)

ODISHA STATE BOARD OF PHARMACY

D. Pharm - II Examination - 2016 (I)

PHARMACEUTICS - II (THEORY)

Time - 3 Hours Full Marks - 80

__________________

(Answer any five questions including question no-1)

1. Fill in the blanks

[1x6

A. (i) Corticosteroids are contraindicated in patients having

(ii) The strong purgatives should be avoided in women during

(iii) Cachets are also known as

(iv) Emulsifying agents reduce between two phases.

(v) Rectal suppositories are generally made from

(vi) Injection should be isotonic & free from foreign particles.

B. Define following

[2x7

(i) Subscription,

(ii) Mixture,

(iii) Tablet Triturate,

(iv) Posology,

(v) Paste,

(vi) Pyrogen,

(vii) I.V. Fluids

2. Define Incompatibility. What are different types of Incompatibility. Describe in brief about the physical incompatibility with examples.

[2+13

3. Define suspension. Explain different types of additives used in the formulation of suspension & differentiate between flocculated & non-flocculated suspension.

[2+9+4

4.(a) Define emulsion. What are different types of emulsion.

[2+1+7

(b) Write short notes on Creaming.

5. Define an ointment, Classify different ointment bases used in the preparation of ointments. Describe each ointment base in detail.

[2+2+11

6. Define the term parenteral products ? Discuss in brief the various tests which are required to be done for the evaluation of parenteral preparation.

[2+13

7. Write short notes on any three.

[5x3

(i) Alkaloidal Incompatibility

(ii) Facial Cosmetics

(iii) Particulate matter monitoring

(iv) Suppositories

ANSWERS TO 2016

1. A.

(i) diabetes/glaucoma/peptic ulcer

(ii) Pregnancy

(iii) Wafer capsule

(iv) Interfacial tension

(v) theobroma oil

(vi) sterile

(i) Subscription : It is that part of prescription which comprises direction to the Pharmacist for preparing the prescription and number of doses to be dispensed.

(ii) Mixture: It is a liquid preparation for oral administration in which drug or drugs are dissolved, suspended or dispersed in a suitable vehicle and generally several doses are contained in a bottle.

(iii) Tablet Triturate: These are the powders which can be moulded into tablets.

(iv) Posology: It is the study of dose. Dose is the quantity of drug which can be administered to a patient to get the desired pharmacological action.

(v) Paste Pastes are semi-solid preparations intended for external application to the skin. The pastes are generally very thick and stiff. They do not melt at ordinary temperature and thus form a protective coating over the area where they are applied. They are used mainly as antiseptic protective or soothing dressings which are often spread on lint before being applied.

(vi) Pyrogen: These are the metabolic product of microorganisms which when enters our body raise the body temperature above normal.

(vii) I.V. Fluids: These are large volume parenteral solutions administered by IV infusion to supply body fluids, electrolytes or to provide nutrition to the body.

2. Define Incompatibility. What are different types of Incompatibility. Describe in brief about the physical Incompatibility with examples.

Ans.

Incompatibility occurs as a result of mixing of two or more antagonistic substances and an undesirable product is formed wich may affect the safety, efficacy and appearance of the pharmaceutical preparation. The interaction of a drug with another drug or of a drug with additives or adjuncts; dosage errors etc. comes under incompatibility. Incompatibility may occur not only during compounding and dispensing but also at any stage during formulation, manufacturing, packaging or administration of drugs.

Types of Incompatibilities:

The incompatibilities are of three types:

(A) Physical incompatibility

(B) Chemical incompatibility

Physical incompatibility:

When two or more than two substances are combined together, a physical change take place and an unacceptable product is formed. Physical incompatibility is usually due to immiscibility, insolubility, precipitate formation or liquefaction of solid materials. These changes which occurs as a result of physical incompatibility are usually visible and can be easily corrected by applying the pharmaceutical skill to obtain a product of uniform dosage, an attractive appearance and having satisfactory therapeutic activity. The physical incompatibilities may be corrected by using any one or more of the following methods:

(i) Change the order of mixing of ingredients of the prescription

(ii) Emulsification

(iii) Addition of suspending agent

(iv) Change in the form of ingredients

(v) By addition, substitution or omission of therapeutically inactive substance to help in compounding of the prescription.

Examples of Physical Incompatibilities and Their Methods of Correction :

(i) Immiscibility: Oils and water are immiscible with each other. They can be made miscible with water by emulsification.

Example:

Castor oil 15ml

Water upto 60ml

Make an emulsion

In this prescription castor oil is immiscible with water. To overcome this incompatibility an emulsifying agent is used to make a good emulsion.

(ii) Insolubility: Insolubility means the inability of material to dissolve in a particular solvent system. The majority of physical incompatibilities are due to insolubility of the inorganic as well as organic compounds in a particular solvent.

The liquid preparation containing indiffusible solids such as chalk, aromatic chalk powder, acetyl salicylic acid, phenacetinzinc oxide and calamine etc. a suspending agent may be incorporated, so as to increase the thickness of the preparation.

Example:

Phenacetin 3gm

Caffeine 1gm

Orange syrup 12ml

Water upto 90ml

Make a mixture

In this prescription phenacetin is an indiffusible substance. Compound powder of tragacanth or mucilage of tragacanth is used as a suspending agent to make a stable suspension.

(iii) Precipitation: A drug in solution may be precipitated, if the solvent in which it is insoluble is added to the solution e.g., resins are insoluble in water. When tincture containing resinous matter is added in water, resin agglomerates forming indiffusible precipitates. This can be prevented by slowly adding the undiluted tincture with vigorous stirring to the diluted suspension or by adding some suitable thickening agent.

Example: Prepare and dispense 100 ml of the following lotion.

Tincture benzoin compound 5.0ml

Glycerin 15.0ml

Rose water upto 100ml

Tincture benzoin compound contain resins. The change in solvent system results in an unavoidable precipitate. Addition of tincture with rapid stirring yields a fine colloidal dispersion. So there is no need of any suspending agent.

(iv) Liquefaction: When certain low melting point solids are mixed together, a liquid or soft mass known as 'eutectic mixtures' is produced. This occurs due to the lowering of the melting point of mixture to below room temperature and liberation of water of hydration. Many chemicals form hydrates, compounds with water of crystallisation, that are stable at room temperature or normal humidity. But these compounds will tend to release their water of hydration under the influence of increasing temperature or decreasing humidity. The medicaments showing this type of behaviour are camphor, menthol, thymol, phenol, chloral hydrate and aspirin. These types of substances create problems when they are dispensed in powder form. These substances can be dispensed by any one of the following methods:

(a) triturate together to form liquid and mixed with an absorbent like light kaolin or light magnesium carbonate to produce free flowing powder.

(b) The individual medicament is powdered separately and mixed with an absorbent and then combined together lightly and filled in suitable containers.

Example

Menthol 5gm

Camphor 5gm

Ammonium chloride 30gm

Light magnesium

carbonate 60gm

Make an insufflation.

In this prescription menthol, camphor and ammonium chloride get liquefied on mixing with each other. To dispense this prescription, mentho, camphor and ammonium chloride are triturated together to form liquid. Add light magnesium carbonate and mix it thoroughly to make free flowing powder.

3. Define suspension. Explain different types of additives used in the formulation of suspension & differentiate between flocculated & non-flocculated suspension.

Ans.

Suspensions are the biphasic liquid dosage form of medicament in which the finely divided solid particles ranging from 0.5 to 5.0 micron are suspended or dispersed in a liquid or seni-solid vehicle. The solid particles constitutes the discontinuous pliase whereas the liquid vehicle constitutes the continuous phase.

Qualities of Good Suspension A well formulated suspension should have the following properties :

1. The dispersed particles should not settle readily and the settled particles should redisperse immediately on shaking.

2. The particles should not form a cake on settling.

3. The viscosity should be such that the preparation can be easily poured.

4. It should be chemically stable.

5. Suspensions for internal use must be palatable and suspensions for external use mast be free from gritty particles and possess other characteristics required for external preparations.

Formulation of Suspensions

Following are the additives which are generally used in the formulation of suspensions:

1. Flocculating agents

2. Suspending agents/thickening agents

3. Wetting agents

4. Dispersing agents

5. Preservative

6. Organoleptic additives

1. Flocculating Agents: When formulating suspensions it must be ensured that the particles are well dispersed in the vehicle. The dispersion can be improved by adding a surfactant which will act by reducing the interfacial tension. For example, if surfactants with negative charges are adsorbed on the particles, prevents or minimises flocculation in the presence of positive ions because of natural repulsion of like charges. Sodium lauryl sulphate and sodium dioctyl sulphosuccinate are examples of this type of surfactants. Non-ionic surfactants also usually assume a negative charge in solution thereby act as effective flocculating agents. Generally non-ionic surfactants are used for dispersing the insoluble particles.

2. Suspending Agens/Thickening Agents : Suspending agents are the substances which are added to a suspension to increase the viscosity of the continuous phase so that the particles remain suspended for a sufficiently long time and it becomes easy to measure an accurate dose.

The semi-synthetic thickening agents widely used include methyl cellulose, carboxy methyl cellulose,hydroxypropyl methyl cellulose, synthetic polymers and gelatin. Sodium carboxy methyl cellulose in concentration of about 3.5% is used in injectable suspensions. Clays such as hydrate aluminium sillicate or magnesium sillicate are also used as suspending agents. Non-ionic substances such as sorbitol, glycerin, sugar or polyethylene glycols may be included to adjust the viscosity of the medium.

3. Wetting Agents: Wetting agents are the substances which reduce the interfacial tension between the solid particles and liquid medium thus producing a suspension of desired quality. This may be achieved by adding a suitable wetting agent. Examples of wetting agents are alcohol in tragacanth mucilage, glycerin and glycols in sodium alginate or bentonite dispersions and polysorbates in oral and parenteral suspensions.

4. Dispersing Agents: The first step in the formulation of any suspensions is to ensure that the particles are dispersed in and wetted by the dispersion medium. In some substances where the surface energy is not sufficient the particles may come together and form larger particles. To overcome this difficulty the substances which are used are known as dispersing agents.

5. Preservative: The presence of suspending agents and medicament which are liable for bacterial growth makes it necessary to incorporate a preservative in suspensions. The commonly used preservatives are benzoic acid, sodium benzoate, methyl paraben and propyl-paraben.

6. Organoleptic Additives Colours, sweetening agents and flavouring agents are used in oral suspensions. Similarly colours and perfumes are incorporated in suspensions meant for external application but these must be compatible with other ingredients.

4.(a) Define emulsion. What are different types of emulsion.

Ans.

An emulsion is a liquid preparation containing two immiscible liquids, one of which is dispersed as minute into the other. The liquid that is broken up into globules is called the dispersed phase or internal phase and the liquid in which the globules are dispersed is known as continuous or external phase. The globules remain dispersed only for a short time and separation takes place quickly upon standing. Therefore a third substance as emulsifying agent is added to the system which forms a film around the globules of the dispersed phase thereby the globules remain scattered indefinitely in the continuous phase and a uniform, stable product is formed. An emulsion may also be defined as a biphasic liquid dosage form of medicament in which two immiscible liquids (generally one of which is water and the other is some lipid or oil) are made miscible by the addition of a third substance known as emulgent or emulsifying agent.

Types of Emulsions

There are two types of emulsions:

(a) Oil in water type (O/W)

(b) Water in oil type (W/O)

In oil in water type emulsions the oil is in the dispersed phase whereas water is in the continuous. phase. These types of emulsions are prepared by using emulsifying agents like gum acacia, tragacanth, methyl cellulose, saponins, synthetic substances and soaps formed from monovalent bases like Na, K and NH Oil in water type emulsions are preferred for internal use because the unpleasant taste and odour is masked by emulsification and oil being in a finely dispersed state is more quickly assimilated in the body.

In water in oil type emulsions, the water is in the dispersed phase whereas oil is in the continuous phase. These types of emulsions are mainly used externally as lotions or creams. Some oil in water type emulsions can also be used externally. The type of emulsifying agent used will determine the kind of emulsions formed. Antiseptics and other medicaments are more effective when used in the form of oil in water type emulsions. When an emollient action is required then water in oil emulsions are used externally. Emulsifying agents like wool fat, resins, bees wax, synthetic compounds and soaps formed from divalent bases like Ca, Mg and Zn are used for the preparation of water in oil emulsions.

Tests for Identification of Type of Emulsion Since both the types (O/W) and (W/O) of emulsions are similar in appearance therefore it is very difficult to differentiate them with naked eye. They can be identified with the help of following tests but no one test gives correct results. Therefore the type of emulsion determined by one method should be confirmed by second method.

(a) Dilution Test: Take a few drops of emulsion in a test-tube and dilute it with 2-3 drops of water. If the water is distributed uniformly in the emulsion then the emulsion is O/W type but if water separates out as a layer then the emulsion is W/O type. Similarly on dilution with oil, the oil will distribute uniformly in W/O emulsion but separates out in O/W type emulsion.

(b) Condictivity Test: Water is a good conductor of electricity whereas oil is non-conductor of electricity. So conductivity test can be performed by dipping a pair of electrodes connected through a low voltage lamp, in the emulsion. On passing an electric current through the electrodes if the bulb glows, the emulsion is O/W type because water is in the continuous phase and current has passed through the water but if the bulb does not glow, the emulsion is W/O type because oil is in the continuous phase and the current has not passed through the oil which has failed to glow the bulb.

(c) Dye-Solubility Test: Mix an oil soluble dye like scarlet red with an emulsion. Place a drop of it ona microscope slide and see under the microscope. If the continuous phase appears to be red, it is W/O emulsion but if scattered slobules appears red and continuous phase colourless it is O/W emulsion. This test can be repeated by using amaranth, a water soluble dye. If the continuous phase colourless it is W/O emulsion.

(d) CoCI, Fitter Paper Test: When a filter paper impregnated with CoCI, and dried (blue) is dipped in an emulsion changes to pink, it indicates that emulsion is O/ W type. This test may fail if emulsionis unstable or breaks in the presence of electrolytes.

(e) Fluorescence Test: When oils are exposed to U.V. rays they flucresce, O/W emulsions exhibit spotty pattern and W/O emulsions fluoresce throughout the field. This method is not always applicable.

(b) Write short notes on Creaming. Ans. In creaming the dispersed globules move upward and form a thick layer at the surface of the emulsion whereas in sedimentation the dispersed globules move downward towards the bottom and form a layer over there. A good example of creaming is when milk is set aside for a new hours, a thick layer of cream forms at the surface. Creaming is a temporary phase because it can be re-distributed by mild shaking or stirring to get a homogeneous product. At the same time creaming is undesirable because a badly creamed emulsion may lead to cracking with complete separation of the two phases. There are many factors which lead to creaming of emulsions but the chief factor is the rising of dispersed globules to the surface of the emulsion. The rate at which the globules will rise to the surface or the rate of creaming is governed by Stoke's law, which may be expressed as follows:

It is evident from the equation that the rate of creaming depends upon the radius of globules, the difference between the densities of the dispersed phase and continuous phase and the viscosity of the dispersion medium. Larger the sizeof the globules more will be creaming and smaller the size of the globules lesser will be creaming because small globules will riese less quickly than large globules. Therefore creaming can be reduced by reducing the size of globules by passing the emulsion through a homogeniser.

The rate of creaming depends upon the difference between the densities of dispersed phase and continuous phase. Greater the difference more will be creaming. Therefore this difference can be reduced but this is rarely possible in practice because it is therapeutically undesirable.

The rate of creaming is inversely proportional to the viscosity of the dispersion medium, therefore this is the most suitable approach for preparing a stable emulsion. The viscosity of the emulsion can be increased,but too high a viscosity is undesirable because it may become difficult to redisperse the materials which have settled and pouring of the too viscous product from its container may be a problem.

The high temperature reduces viscosity which encourages creaming, therefore emulsion should be stored in a cool place. Freezing should be avoided which may lead to cracking.

5. Define an ointment, Classify different ointment bases used in the preparation of ointments. Describe each ointment base in detail.

Ans.

The ointment base is that substance or part of an ointment, which serves as carrier or vehicle for the medicament. An ideal ointment base should possess the following properties:

(i) It should be inert, odourless and smooth.

(ii) It should be physically and chemically stable.

(iii) It should be compatible with the skin and with the incorporated medicaments.

(iv) It should be of such a consistency that it spreads and softens when applied to the skin with stress.

(v) It should not retard healing of the wound. (vi) It should not produce irritation or sensitisation of the skin.

Classification of Ointment Bases :

(i) Oleaginous bases

(ii) Absorption bases

(iii) Emulsion bases

(iv) Water soluble bases

(i) Oleaginous bases: These bases consist of water insoluble, hydrocarbons, vegetable oils, animal fats and waxes. The constituents of hydrocarbon bases are soft paraffin, hard paraffin and liquid paraffin.

(a) Petrolatum (soft paraffin): It is a purified mixture of semi-solid hydrocarbons obtained from petroleum. There are two varieties of soft paraffin, one is yellow soft paraffin and other is white soft paraffin. White soft paraffin is prepared by bleaching yellow paraffin. Both these soft paraffin have melting point 38°C to 56°C. White soft paraffin is used when the medicament is white or colourless. White soft paraffin is never used in the preparation of ophthalmic ointments because the white soft paraffin may contain small traces of bleaching agent which are generally left over after bleaching the yellow soft paraffin. Hence, the white soft paraffin may cause irritation to the eye.

(b) Hard paraffin: It is a purified mixture of solid hydrocarbons obtained from petrolatum. It is colourless or white translucent, odourless, tasteless wax like substance. It is used to harden or soften the ointment base.

(c) Liquid paraffin : It consists of a mixture of liquid hydrocarbons and obtained from petroleum by distillation. It is also known as white mineral oil or liquid petroleum. It is a colourless, odourless, tasteless and transparent oily liquid. It is soluble in ether and chloroform but insoluble in water and alcohol. It is used along with hard paraffin and soft paraffin to get a desired consistency of the ointment. The oleaginous bases are losing their importance nowadays for the following reasons:

(i) They are greasy.

(ii) They are sticky and are difficult to remove both from skin and clothing.

(iii) They retain body heat which may produce an uncomfortable feeling or warmth.

(iv) They do not help in the absorption of medicamants.

(v) They prevent drainage on oozing areas and also prevent evaporation of cutaneous secretions along with perspiration.

(ii) Absorption bases: These bases are generally anhydrous substances which have the property of absorbing (emulsifying) considerable quantities of water but still retaining their ointment-like. consistency. The absorption bases are of two types :

(a) Non-emulsified bases

(b) Water in oil emulsions

The non-emulsified bases absorb water and aqueous solutions producing w/o emulsions e.g., wool fat, wool alcohol, beeswax and cholesterol. The water in oil emulsions are capable of absorbing more water and have the properties of non-emulsified bases e.g.. hydrous wool fat (lanolin).

(i) Wool fat: It is the purified fat-like substance obtained from the wool of sheep. It is also known as anhydrous lanolin. It can absorb about 50% of its weight of water. So it is used in ointments where the proportion of water or aqueous liquids to be incorporated in hydrocarbon base is too large. It is an important constituent to simple ointment base and eye ointment base.

(ii) Hydrous wool fat: It is the purified fat like substance obtained from wool of sheep. It is also known as lanolin. It is insoluble in water but soluble in ether and chloroform. Hydrous wool fat is a mixture of 70% w/w wool fat and 30% w/w/ purified water. It is used alone as emollient and as an ingredient of several other ointments

(iii) Wool alcohol: It is obtained from wool fat by treating it with alkali and separating the fraction containing cholesterol and other alcohols. It contains not less than 30% of cholesterol. It is used as an emulsifying

agent for the preparation of w/o emulsion. It is also used to improve the texture, stability and emollient properties of o/w emulsions.

(iv) Beeswax: It is purified wax obtained from honey comb of bees. It is available as yellow beeswax and white beeswax. White beeswax is obtained by bleaching the yellow beeswax. It is used as a stiffening agent in pastes and ointments. These bases have following advantages:

(i) These bases are compartible with large number of medicaments.

(ii) These bases can absorb a large quantity of water of aqueous substances.

(iii) These bases are relatively heat stable.

(iv) These bases may be used in their anhydrous form or in emulsified form. These bases are quite greasy, but these can be easily removed from the skin as compared to oleaginous bases.

(iii) Emulsion Bases: These bases are semisolid or have a cream like consistency. Both o/w and w/o emulsions are used as ointment base. The oil in water type of emulsion bases are more popular because these can be easily removed from the skin or clothes by washing with water. The w/o type of bases are greasy and sticky. The emulsifying ointment is prepared from emulsifying wax, white soft paraffin and liquid paraffin.

(iv) Water Soluble Bases: These are commonly known as "greaseless ointment bases". The water soluble bases consist of water soluble ingredients, such as, polyethylene glycol polymers which are popularly known as "carbowaxes". The carbowaxes are water soluble, non-volatile and inert substances. Depending upon the mlecular weight, carbowaxes are available in different. consistencies i.e., liquids, liquids, semisolids and solids. Their molecular weight varies from 200 to 8000. By mixing different carbowaxes, ointments of varying consistencies can be obtained. Tragacanth, gelatin, pectin, cellulose derivatives, bentonite, magnesium-aluminium silicate and sodium alginate are also used as water soluble bases.

6. Define the term parenteral products? Discuss in brief the various tests which are required to be done for the evaluation of parenteral preparation.

Ans.

Parenteral preparations are those pharmaceutical products that are given by other than oral routes. Transfusion fluids and injections are parenteral preparations. Injections are the sterile solutions