Semisolid Dosage Forms by BIBEK SINGH MAHAT

SEMISOLID DOSAGE FORMSSEMISOLID DOSAGE FORMS

Phr. Bibek Singh Mahat M. Pharm. (Industrial)

6/27/2012 [email protected]

SEMISOLID DOSAGE FORMSSEMISOLID DOSAGE FORMSOintments:-Type of ointments, classification and selection of dermatological vehicles. Preparation and stability of ointments by the following processes: (i) stability of ointments by the following processes: (i) Trituration, (ii) Fusion, (iii) Chemical reaction, (iv) emulsification.

Pastes: Differences between ointments and pastes. Bases of pastes. Preparation of pastes and their p p ppreservation.

Jellies: An introduction to the different types of jellies Jellies: An introduction to the different types of jellies and their preparation.

An elementary study of poultice.


SEMISOLID DOSAGE FORMSSEMISOLID DOSAGE FORMSOintments are soft semisolid preparations meant for external application to the skin or mucous

bmembrane.

They usually contains medicament which is either They usually contains medicament which is either dissolved or suspended in the base.

They have emollient and protective action.

Creams are semisolid emulsions and are generally of softer consistency and lighter than ointments.

They are less greasy and are easy to apply.6/27/2012 [email protected]

SEMISOLID DOSAGE FORMSSEMISOLID DOSAGE FORMSPastes are semisolid preparations for external application that differ from similar products in containing a high proportion of finely powdered medicaments.

They are stiffer and are usually employed for their protective action and for their ability to absorb serous discharges from action and for their ability to absorb serous discharges from skin lesions.

Thus when protective rather than therapeutic action is Thus when protective, rather than therapeutic action is desired, the formulation pharmacists will favour a paste, but when therapeutic action is required, he will prefer ointments and creams.and creams.

Jellies are transparent or translucent, non-greasy, semisolid preparation mainly used externally The gelling agent may be preparation mainly used externally.The gelling agent may be gelatin, starch, tragacanth, sodium alginate or cellulose derivative (e.g. carboxy methyl cellulose).


OINTMENTOINTMENT

Definition: Definition:

Ointments are semisolid preparations for Ointments are semisolid preparations for application to the skin or mucosae.

The ointment bases are almost always anhydrous and generally contains one or more medicaments in suspension or solution.


OINTMENTOINTMENTCharacteristics of an ideal ointment:1. It should be chemically and physically stable.1. It should be chemically and physically stable.2. It should be smooth and free from grittiness. 3 It should melt or soften at body temperature 3. It should melt or soften at body temperature

and be easily applied.Th b h ld b i i d h ld 4. The base should be non-irritant and should have no therapeutic action.

5. The medicament should be finely divided and uniformly distributed throughout the base.


Classification of ointmentsClassification of ointmentsAccording to their therapeutic properties based on penetration of skin.pOintments classified according to their therapeutic properties based on penetration therapeutic properties based on penetration are as follows:

(a) Epidermic, (b) E d d i (b) Endodermic, (c) Diadermic


Classification of ointmentsClassification of ointments(a) Epidermic ointments

These ointments are intended to produce their action on the surface of the skin and their action on the surface of the skin and produce local effect.

They are not absorbed.

They acts as protectives, antiseptics and y p pparasiticides.


Classification of ointmentsClassification of ointments(b) Endodermic ointments

These ointments are intended to release the These ointments are intended to release the medicaments that penetrate into the skin. They are partially absorbed and acts as They are partially absorbed and acts as emollients, stimulants and local irritants.

(c) Diadermic ointmentsThese ointments are intended to release the medicaments that pass through the skin and produce systemic effects.


Classification of ointmentsClassification of ointmentsAccording to therapeutic uses the ointments are classified as follows:

(i) Acne treatment :resorcinol, sulfur.

(ii) Antibiotics :Used to kill microorganisms.e.g. bacitracin, chlortetracycline, neomycin.

(iii) Antieczematous :Used to stop oozing and exudation from vesicles on the skin.e.g. hydrocortisone, coal tar, ichthamol, salicylic acid.e.g. hydrocortisone, coal tar, ichthamol, salicylic acid.

(iv) Antifungal :Used to inhibit or kill the fungi.e g benzoic acid salicylic aid nystatin clotrimazole etce.g. benzoic acid, salicylic aid, nystatin, clotrimazole, etc.

(v) Anti-inflammatory :Used to relieve inflammatory, allergic and pruritic conditions of the skinpruritic conditions of the skine.g. betamethasone valerate, hydrocortisone, triamcinoloneacetonide



(vi) Antipruritic :Used to relieve itching.e.g. benzocaine, coal tar.g ,

(vii) Antiseptic :Used to stop sepsis.e.g. ammoniated mercury, zinc oxide.e.g. ammoniated mercury, zinc oxide.

(vii) Astringent :Reduces the secretion of glands or discharge from skin surface.skin surface.e.g. calamine, zinc oxide, aluminium acetate and subacetate, acetic acid and tannic acid.

(ix) Counter irritant These are applied locally to irritate the intact skin, thus reducing or relieving another irritation or deep seated pain. e.g. capsicum oleoresin, iodine (Iodex), methyl salicylate.

(x) Dandruff treatment :e.g. salicylic acid and cetrimide (cetyltrimethyl ammonium bromide) 6/27/2012 [email protected]


(xi) Emollient :Used to soften the skin (for example in the dry season).e.g. soft paraffin

(xii) Keratolytic Used to remove or soften the horny layer of the skin.e.g. resorcinol, salicylic acid and sulfur.

(xi) Keratoplastic :Tends to increase the thickness of horny layer e.g. coal tar.

(xii) Parasiticide :These ointments destroy or inhibit living infestations such as lice and ticks.e.g. benzyl benzoate, gamma-benzene hexachloride (GBH), sulfur etc.e.g. benzyl benzoate, gamma benzene hexachloride (GBH), sulfur etc.

(xiii) Protective :Protects the skin from moisture, air, sun rays or other substances such as soaps or chemicals.e.g. silicones, titanium dioxide, calamine, zinc oxide, petrolatum.


OINTMENT BASESOINTMENT BASESThe ointment base is that substance or part of an ointment preparation which serves as carrier or vehicle for the medicamentmedicament.

An ideal ointment base should be inert, stable, smooth, An ideal ointment base should be inert, stable, smooth, compatible with the skin, non-irritating and should release the incorporated medicaments readily.

Classification of ointment bases:1 Oleaginous bases1. Oleaginous bases2. Absorption bases3. Water-miscible bases3. Water miscible bases4. Water soluble bases


OINTMENT BASESOINTMENT BASESOLEAGINOUS BASES

These bases consists of oils and fats The most important are the These bases consists of oils and fats. The most important are the Hydrocarbons i.e. petrolatum, paraffins and mineral oils.The animal fat includes lard.Th bi ti f th t i l d d t f The combination of these materials can produce a product of desired melting point and viscosity.

(a) Petrolatum (Soft paraffin)This is a purified mixture of semi-solid hydrocarbons obtained from petroleum or heavy lubricating oil.Yellow soft paraffin (Petrolatum; Petroleum jelly)This a purified mixture of semisolid hydrocarbons obtained from petroleum. It may contain suitable stabilizers like, antioxidants e.g. a-tocopherolIt may contain suitable stabilizers like, antioxidants e.g. a tocopherol(Vitamin E), butylated hydroxy toluene (BHT) etc.Melting range : 38 to 56˚C.


OINTMENT BASESOINTMENT BASESOLEAGINOUS BASESWhite soft paraffin (White petroleum jelly, White petrolatum)

Thi ifi d i f i lid h d b b i d This a purified mixture of semisolid hydrocarbons obtained from petroleum, and wholly or partially decolorized by percolating the yellow soft paraffin through freshly burned p g y p g ybone black or adsorptive clays.

˚Melting range : 38 to 56˚CUse: The white form is used when the medicament is colourless white or a pastel shade colourless, white or a pastel shade. This base is widely used in

1. Dithranol ointment B.P.2. Ammoniated Mercury and Coal tar ointment B.P.3. Zinc ointment B.P. 6/27/2012 [email protected]

OINTMENT BASESOINTMENT BASESOLEAGINOUS BASES

(b) Hard paraffin (Paraffin)

This is a mixture of solid hydrocarbons obtained from petroleum.It is colourless or white, odorless, translucent, wax-like substance. It solidifies between 50 and 57˚C and is used to stiffen ointment bases.


OINTMENT BASESOINTMENT BASES(c) Liquid paraffin (Liquid petrolatum,; White mineral

oil)

It is a mixture of liquid , hydrocarbons obtained from petroleum. It is transparent, colourless, odourless, viscous liquid.On long storage it may oxidize to produce peroxides and therefore, it may contain tocopherol or BHT as antioxidants.It is used along with hard paraffin and soft paraffin to get a desired It is used along with hard paraffin and soft paraffin to get a desired consistency of the ointment. Tubes for eye, rectal and nasal ointments have nozzles with narrow

ifi h h hi h i i diffi l l i i orifices through which it is difficult to expel very viscous ointments without the risk of bursting the tube. To facilitate the extrusion up-to 25% of the base may be replaced by p y p yliquid paraffins.


OINTMENT BASESOINTMENT BASESAdvantages of hydrocarbons bases:1. They are not absorbed by the skin. 2. They remain on the surface as an occlusive layer that

restricts the loss of moisture hence, keeps the skin soft.3 They are sticky hence ensures prolonged contact between 3. They are sticky hence ensures prolonged contact between

skin and medicament.4. They are almost inert. They consist largely of saturated

hydrocarbons, therefore, very few incompatibilities and little tendency of rancidity are there.

5 They can withstand heat sterilization hence sterile 5. They can withstand heat sterilization, hence, sterile ophthalmic ointments can be prepared with it.

6. They are readily available and cheap.y y p


OINTMENT BASESOINTMENT BASESDisadvantages of hydrocarbon bases;1. It may lead to water logging followed by maceration of the

ki if li d f l d i dskin if applied for a prolonged period.2. It retains body heat, which may produce an uncomfortable

feeling of warmth.feeling of warmth.3. They are immiscible with water; as a result rubbing onto the

surface and removal after treatment both are difficult.4. they are sticky, hence makes application unpleasant and leads

to contamination of clothes.5 Water absorption capacity is very low hence these bases are 5. Water absorption capacity is very low, hence, these bases are

poor in absorbing exudates from moist wounds.


OINTMENT BASESOINTMENT BASESABSORPTION BASE

The term absorption base is used to denote the water b bi l if i f h b d absorbing or emulsifying property of these bases and not to

describe their action on the skin.

These bases (some times called emulsifiable ointment bases) are generally anhydrous substances which have the property of b b ( l f ) d bl f absorbing (emulsifying) considerable quantity of water yet

retaining its ointment-like consistency.

Preparations of this type do not contain water as a component of their basic formula but if water is incorporated a W/O emulsion results.


OINTMENT BASESOINTMENT BASESABSORPTION BASEWool Fat (anhydrous lanolin)

It is the purified anhydrous fat like substance obtained from the wool of sheep.·It is practically insoluble in water but can absorb water uptoIt is practically insoluble in water but can absorb water upto50% of its own weight. Therefore it is used in ointments the proportion of water or aqueous liquids to be incorporated in hydrocarbon base is too large.Due to its sticky nature it is not used alone but is used along Due to its sticky nature it is not used alone but is used along with other bases in the preparation of a number of ointments.e.g. Simple ointment B.P. contains 5% and the B.P. eye ointment g p ybase contains 10% woolfat.


OINTMENT BASESOINTMENT BASESHydrous Wool Fat (Lanolin)It is a mixture of 70 % w/w wool fat and 30 % w/w purified water. It is a w/o emulsion. Aqueous liquids can be emulsified with it.It is used alone as an emollient.Example:- Hydrous Wool Fat Ointment B.P.C., Calamine Coal Tar Ointment.Wool AlcoholIt is the emulsifying fraction of wool fat. Wool alcohol is obtained from wool fat by treating it with alkali and

f separating the fraction containing cholesterol and other alcohols. It contains not less than 30% of cholesterol.Use:-It is used as an emulsifying agent for the preparation of w/o emulsions and is used to absorb water in ointment bases.It is also used to improve the texture, stability and emollient

ti f / l iproperties of o/w emulsions.Examples :- Wool alcohol ointment B.P. contains 6% wool alcohol and hard, liquid and soft paraffin.6/27/2012 [email protected]

OINTMENT BASESOINTMENT BASESBeeswax

It is purified wax, obtained from honey comb of bees.It contains small amount of cholesterol. It is of two types: (a) yellow beeswax and (b) white beeswax.

Use:-Beeswax is used as a stiffening agent in ointment preparations.Beeswax is used as a stiffening agent in ointment preparations.Examples:-Paraffin ointment B.P.C. contains beeswax.

CholesterolIt is widely distributed in animal organisms It is widely distributed in animal organisms. Wool fat is also used as a source of cholesterol.Use:- It is used to increase the water absorbing power of an ointment baseointment base.Example:- Hydrophilic petroleum U.S.P. contains:Cholesterol 3%Stearyl alcohol 3%Stearyl alcohol 3%White beeswax 8%White soft paraffin 86% 6/27/2012 [email protected]

OINTMENT BASESOINTMENT BASESAdvantages of absorption bases:1. They are less occlusive nevertheless, are good emollient.2. They assist oil soluble medicaments to penetrate the skin.3. They are easier to spread.4 Th tibl ith j it f th di t4. They are compatible with majority of the medicaments.5. They are relatively heat stable.6 The base may be used in their anhydrous form or in 6. The base may be used in their anhydrous form or in

emulsified form.7. They can absorb a large quantity of water or aqueous

substances.Disadvantages: Inspite of their hydrophilic nature, absorption bases are difficult to washbases are difficult to wash.


OINTMENT BASESOINTMENT BASESWATER MISCIBLE BASES

They are miscible with an excess of water. Oi d f i ibl b il d f Ointments made from water-miscible bases are easily removed after use.There are three official anhydrous water-miscible ointment bases:-yExample:-

1. Emulsifying ointment B.P. - contains anionic emulsifier.C f f2. Cetrimide emulsifying ointment B.P. - contains cationic emulsifier

3. Cetomacrogol emulsifying ointment B.P. - contains non-ionic emulsifier

Uses: they are used to prepare o/w creams and are easily removable ointment bases

C d B i A id Oi t t (Whitfi ld’ Oi t t) e.g. Compound Benzoic Acid Ointment (Whitfield’s Ointment) -used as antifungal ointment.


OINTMENT BASESOINTMENT BASESWATER MISCIBLE BASES

Advantages of water miscible bases:1. Readily miscible with the exudates from lesions.2 R d d i t f ith l ki f ti2. Reduced interference with normal skin function.3. Good contact with the skin, because of their surfactant

content.4. High cosmetic acceptability, hence there is less likelihood of

the patients discontinuing treatment.5. Easy removal from the hair.


OINTMENT BASESOINTMENT BASESWATER SOLUBLE BASES

Water soluble bases contain only the water soluble ingredients and not the fats or other greasy substances, hence, they are known as grease-less bases.they are known as grease less bases.

Water soluble bases consists of water soluble ingredients such as polyethylene glycol polymers (PEG) which are popularly known as “carbowaxes” and commercially known as “macrogols”.macrogols .

They are a range of compounds with the general formula:y g p gCH2OH . (CH2OCH2) n CH2OH


OINTMENT BASESOINTMENT BASESWATER SOLUBLE BASES

Th PEG i t f l d ti d t f The PEGs are mixtures of polycondensation products of ethylene and water and they are described by numbers representing their average molecular weights. Like the paraffin hydrocarbons they vary in consistency from viscous liquids to waxy solids.Example:-p

1. Macrogols 200, 300, 400 - viscous liquids2. Macrogols 1500 - greasy semi-solids3. Macrogols 1540, 3000, 4000, 6000 - waxy solids.

Different PEGs are mixed to get an ointment of desired consistency. 6/27/2012 [email protected]

OINTMENT BASESOINTMENT BASESAdvantages of PEGs as ointment base:

1. They are water soluble; hence, very easily can be removed from the skin and readily miscible with tissue exudates.

2 Helps in good absorption by the skin2. Helps in good absorption by the skin.3. Good solvent properties. Some water-soluble dermatological

drugs, such as salicylic acid, sulfonamides, sulfur etc. are soluble in this bases.

4. Non-greasy.Th d h d l idif i bi l 5. They do not hydrolyze, rancidify or support microbial growth.

6. Compatibility with many dermatological medicaments.6. Compatibility with many dermatological medicaments.


OINTMENT BASESOINTMENT BASESDisdvantages of PEGs as ointment base:

1. Limited uptake of water. Macrogols dissolve when the proportion of water reaches about 5%.

2 Reduction in activity of certain antibacterial agents e g 2. Reduction in activity of certain antibacterial agents, e.g. phenols, hydroxybenzoates and quaternary compounds.

3. Solvent action on polyethylene and bakelite containers and closures.

4. Certain other substances which are used as water soluble ointment bases include tragacanth gelatin pectin silica gel ointment bases include tragacanth, gelatin, pectin, silica gel, sodium alginate, cellulose derivatives, etc.


OINTMENT BASESOINTMENT BASESFACTORS GOVERNING SELECTION OF

AN IDEAL OINTMENT BASE

1. DERMATOLOGICAL FACTORS

2. PHARMACEUTICAL FACTORS


Factors Governing Selection (Ideal Ointment Base)Factors Governing Selection (Ideal Ointment Base)D l i l fDermatological factors

(a) Absorption and Penetration:‘P i ’ f h d h ki i ‘Penetration’ means passage of the drug across the skin i.e. cutaneouspenetration, and ‘absorption’ means passage of the drug into blood stream.·Medicaments which are both soluble in oil and water are most readily yabsorbed though the skin.·Whereas animal and vegetable fats and oils normally penetrate the skin.·Animals fats, e.g. lard and wool fat when combined with water, penetrates th kithe skin.·o/w emulsion bases release the medicament more readily than greasy bases or w/o emulsion bases.

(b) Effect on the skinGreasy bases interfere with normal skin functions i.e. heat radiation and sweating. They are irritant to the skin.o/w emulsion bases and other water miscible bases produce a cooling effect due to the evaporation of water.


Factors Governing Selection (Ideal Ointment Base)Factors Governing Selection (Ideal Ointment Base)

Dermatological factors

( ) Mi ibilit ith ki ti d (c) Miscibility with skin secretion and serumSkin secretions are more readily miscible with emulsion bases than with greasy bases. Due to this the drug is more rapidly and completely

l d h kireleased to the skin.

(d) Compatibility with skin secretions:The bases used should be compatible with skin secretions and should have pH about 5.5 because the average skin pH is around 5.5. Generally neutral ointment bases are preferred.

(e) Non-irritantAll bases should be highly pure and bases specially for eye ointments All bases should be highly pure and bases specially for eye ointments should be non-irritant and free from foreign particle.


Factors Governing Selection (Ideal Ointment Base)Factors Governing Selection (Ideal Ointment Base)

Dermatological factors

(f) Emollient properties(f) Emollient propertiesDryness and brittleness of the skin causes discomfort to the skin therefore, the bases should keep the skin moist. For this purpose water and humectants such as glycerin, propylene glycol are used. Ointments and humectants such as glycerin, propylene glycol are used. Ointments should prevent rapid loss of moisture from the skin.

(g) Ease of application and removal(g) Ease of application and removalThe ointment bases should be easily applicable as well as easily removable from the skin by simple washing with water. Stiff and sticky ointment b i h f t d th ki d d i bbi l bases require much force to spread on the skin and during rubbing newly formed tissues on the skin may be damaged.


Factors Governing Selection (Ideal Ointment Base)Factors Governing Selection (Ideal Ointment Base)Pharmaceutical factors

(a) StabilityFats and oils obtained from animal and plant sources are prone to p poxidation unless they are suitably preserved. Due to oxidation odour comes out. This type of reactions are called rancidification. Lard, from animal origin, rancidify rapidly. Soft paraffin, simple ointment and paraffin ointment are inert and stable. Liquid paraffin is also stable but after prolonged storage it gets oxidized. Therefore, an antioxidant like tocopherol (Vit -E) may be i t d Oth ti id t th b d b t l t dincorporated. Other antioxidants those may be used are butylatedhydroxy toluene (BHT) or butylated hydroxy hydroxy anisole (BHA).

(b) Solvent propertiesMost of the medicaments used in the preparation of ointments are insoluble in the ointment bases therefore, they are finely powdered and are distributed uniformly throughout the base.


Factors Governing Selection (Ideal Ointment Base)Factors Governing Selection (Ideal Ointment Base)Ph i l fPharmaceutical factors

(c) Emulsifying propertiesHydrocarbon bases absorbs very small amount of water.Wool fat can take about 50% of water and when mixed with other fats can take up several times its own weight of aqueous solution.Emulsifying ointment, cetrimide emulsifying ointment and cetomacrogol emulsifying ointment are capable of absorbing considerable amount of water, forming w/o creams.

(d) ConsistencyThe ointments produced should be of suitable consistency. They should neither be hard nor too soft They should withstand should neither be hard nor too soft. They should withstand climatic conditions. Thus in summer they should not become too soft and in winter not too hard to be difficult to remove from the container and spread on the skin.The consistency of an ointment base can be controlled by varying the ratio of hard and liquid paraffin.


End Of Part 1

Ointment Base

Part 2 Preparation Of OintmentsPreparation Of Ointments


PREPARATION OF OINTMENTSPREPARATION OF OINTMENTS

A well-made ointment is :-

a. Uniform throughout i.e. it contains no lumps of separated high melting point ingredients of the base, there is no high melting point ingredients of the base, there is no tendency for liquid constituents to separate and insoluble powders are evenly dispersed.

b. Free from grittiness, i.e. insoluble powders are finely subdivided and large lumps of particles are absent. Methods subdivided and large lumps of particles are absent. Methods of preparation must satisfy this criteria.


PREPARATION OF OINTMENTSPREPARATION OF OINTMENTS

Two mixing techniques are frequently used in making ointments:ointments:

1. Fusion, in which ingredients are melted together and stirred 1. Fusion, in which ingredients are melted together and stirred to ensure homogeneity.

2. Trituration, in which finely-subdivided insoluble medicaments are evenly distributed by grinding with a small amount of the base or one of its ingredients followed by amount of the base or one of its ingredients followed by dilution with gradually increasing amounts of the base.


1. Ointments prepared by Fusion method:1. Ointments prepared by Fusion method:--When an ointment base contains a number of solid ingredients such as white beeswax, cetyl alcohol, stearylalcohol, stearic acid, hard paraffin, etc. as components of the base, it is required to melted them. The melting can be done in two methods:

Method-IMethod IThe components are melted in the decreasing order of their melting point i.e. the higher m. p. substance should be melted first the substances with next melting point and so on first, the substances with next melting point and so on.

The medicament is added slowly in the melted ingredients and stirred thoroughly until the mass cools down and homogeneous product is formed.

This will avoid over-heating of substances having low melting point. 6/27/2012 [email protected]

1. Ointments prepared by Fusion method:1. Ointments prepared by Fusion method:--

Method-II

All the components are taken in subdivided state and melted together.together.

The maximum temperature reached is lower than Method-I, p ,and less time was taken possibly due to the solvent action of the lower melting point substances on the rest of the ingredientsingredients.



Cautions:-

Melting time is shortened by grating waxy components (i.e. beeswax, wool alcohols, hard-paraffin, higher fatty alcohols and emulsifying waxes) by stirring during melting and by lowering the dish as far as possible into the water bath so that the maximum dish as far as possible into the water bath so that the maximum surface area is heated.

The surface of some ingredients discolors due to oxidation e g The surface of some ingredients discolors due to oxidation e.g. wool fats and wool alcohols and this discolored layers should be removed before use.

After melting, the ingredients should be stirred until the ointment is cool, taking care not to cause localized cooling, e.g. by using a cold spatula or stirrer, placing the dish on a cold surface (e.g. a plastic bench top) or transferring to a cold container before the plastic bench top) or transferring to a cold container before the ointment has fully set. If these precautions are ignored, hard lumps may separate.



Cautions:-

Vigorous-stirring, after the ointment has begun to thicken, causes excessive aeration and should be avoided.

Because of their greasy nature, many constituents of ointment bases pickup dirt during storage, which can be seen after melting. This is removed from the melt by allowing it to sediment and This is removed from the melt by allowing it to sediment and decanting the supernatant, or by passage through muslin supported by a warm strainer. In both instances the clarified liquid is collected in another hot basin.qu s co ecte a ot e ot bas .

If the product is granular after cooling, due to separation of high m p constituents it should be re melted using the minimum of m.p. constituents, it should be re-melted, using the minimum of heat, and again stirred and cooled.


1. Ointments prepared by Fusion method:1. Ointments prepared by Fusion method:--Example:(i) . Simple ointment B.P. contains1 Wool fat 50g1. Wool fat 50g2. Hard paraffin 50g3. Cetostearyl alcohol 50g4. White soft paraffin 850g

Type of preparation: Absorption ointment base

Procedure:Hard paraffin and cetostearyl alcohol on water-bath. p yWool fat and white soft paraffin are mixed and stirred until all the ingredients are melted.If required decanted or strained and stirred until cold and If required decanted or strained and stirred until cold and packed in suitable container.


1. Ointments prepared by Fusion method:1. Ointments prepared by Fusion method:--(ii) Paraffin ointment base

Type of preparation : Hydrocarbon ointment base(iii) W l l h l i t t B P(iii) Wool alcohols ointment B.P.

Type of preparation: Absorption base(iv) Emulsifying ointment B P(iv) Emulsifying ointment B.P.

Type of preparation: Water-miscible ointment base.(v) Macrogol ointment B.P.C( ) g

Type of preparation: Water soluble ointment baseFormula: Macrogol 4000Liquid Macrogol 300Method: Macrogol 4000 is melted and previously warmed li id l 300 i dd d liquid macrogol 300 is added. Stirred until cool.


2. OINTMENT PREPARED BY TRITURATION2. OINTMENT PREPARED BY TRITURATION

This method is applicable in the base or a liquid present in small amount.

1. Solids are finely powdered are passed through a sieve (# y p p g (250, # 180, #125).

2. The powder is taken on an ointment-slab and triturated with a small amount of the base with a small amount of the base.

3. A steel spatula with long, broad blade is used. 4. To this additional quantities of the base are incorporated

and triturated until the medicament is mixed with the base.5. Finally liquid ingredients are incorporated. 6 To avoid loss from splashing a small volume of liquid is 6. To avoid loss from splashing, a small volume of liquid is

poured into a depression in the ointment an thoroughly incorporated before more is added in the same way.

7 S l hi i il t ll d i t th 7. Splashing is more easily controlled in a mortar than on a tile.


2. OINTMENT PREPARED BY TRITURATION2. OINTMENT PREPARED BY TRITURATION

Example:(i) Whitfield ointment

(Compound benzoic acid ointment B.P.C.)( p )

1. Formula: Benzoic acid, in fine powder 6gm2. Salicylic acid, in fine powder 3gm3. Emulsifying ointment 91gm

Method: 1. Benzoic acid and salicylic acid are sieved through No. 180

sieves. 2. They are mixed on the tile with small amount of base and

levigated until smooth and dilute gradually.g g y

(ii) Salicylic acid sulphur ointment B.P.C.6/27/2012 [email protected]

3. OINTMENT PREPARATION BY CHEMICAL REACTION3. OINTMENT PREPARATION BY CHEMICAL REACTION

Chemical reactions were involved in the preparation of several famous ointments of the past, e.g. Strong Mercuric Nitrate Ointment, both of the 1959 B.P.C.Nitrate Ointment, both of the 1959 B.P.C.

(a) Ointment containing free iodine( ) gIodine is only slightly soluble in most fats and oils but readily soluble.I d d l l bl d l f Iodine is readily soluble in concentrated solution of potassium iodide due to the formation of molecular complexes KI.I2, KI.2I2, KI.3I2 etc.pThese solutions may be incorporated in absorption-type ointment bases.e.g. Strong Iodine Ointment B.Vet.C



Strong Iodine Ointment B. Vet. C (British Veterinary Pharmacopoeia) is used to treat ringworm ( y p ) gin cattle. It contains free iodine.

At ti thi t f i t t d tAt one time this type of ointments were used as counter-irritants in the treatment of human rheumatic diseases but they were not popular because:-

(i) They stain the skin a deep red color.

(ii) Due to improper storage the water dries up and the iodine crystals irritate the skin, hence glycerol was some ti t di l th i di t i i did l times to dissolve the iodine-potassium iodide complex instead of water.



Example: Strong Iodine Ointment B. Vet. C.

1. Iodine2 Wool fat2. Wool-fat3. Yellow soft paraffin4. Potassium iodide5. Water



Strong Iodine Ointment B. Vet. C.

P dProcedure:(i) KI is dissolved in water. I2 is dissolved in it.(ii) Wool fat and yellow soft paraffin are melted together (ii) Wool-fat and yellow soft paraffin are melted together over water bath. Melted mass is cooled to about 40˚C.(iii) I2 solution is added to the melted mass in small quantities at a time with continuos stirring until a uniform mass is obtained.(iv) It is cooled to room temperature and packed(iv) It is cooled to room temperature and packed.

Use: - Ringworm in cattle.Use: Ringworm in cattle.



(b) Ointment containing combined iodine

Fi d il d bl d i l f b b i di Fixed oils and many vegetable and animal fats absorb iodine which combines with the double bonds of the unsaturated constituents, e.g.gCH3.(CH2) 2.CH = CH.(CH2) 7.COOH + I2 ® CH3.(CH2) 2.CHI CHI.(CH2) 7.COOH

Oleic acid di-iodostearic acid

Example: Non-staining Iodine Ointment B.P.C. 1968 IodineArachis OilArachis OilYellow Soft Paraffin



Method:1. Iodine is finely powdered in a glass mortar and required amount

is added to the oil in a glass-stoppered conical flask and stirred is added to the oil in a glass stoppered conical flask and stirred well.

2. The oil is heated at 50C in a water-bath and stirred continually. Heating is continued until the brown color is changed to Heating is continued until the brown color is changed to greenish-black; this may take several hours.

3. From 0.1g of the preparation the amount of iodine is determined by B.P.C. method and the amount of soft paraffin base is calculated to give the product the required strength.

4. Soft paraffin is warmed to 40C. The iodized oil is added and pmixed well. No more heat is applied because this causes deposition of a resinous substance.

5 The preparation is packed in a warm wide mouthed amber color 5. The preparation is packed in a warm, wide-mouthed, amber color, glass bottle. It is allowed to cool without further stirring.


4. PREPARATION OF OINTMENTS BY EMULSIFICATION4. PREPARATION OF OINTMENTS BY EMULSIFICATION

A l l h h d An emulsion system contain an oil phase, an aqueous phase and an emulsifying agent.For o/w emulsion systems the following emulsifying agents are used:used:

1. water soluble soap2. cetyl alcohol3 l l t t3. glyceryl monostearate4. combination of emulsifiers: triethanolamine stearate + cetyl

alcohol5 non ionic emulsifiers: glyceryl monostearate glyceryl monooelate 5. non-ionic emulsifiers: glyceryl monostearate, glyceryl monooelate,

propylene glycol stearateFor w/o emulsion creams the following emulsifiers are used:

1 polyvalent ions e g magnesium calcium and aluminium are used1. polyvalent ions e.g magnesium, calcium and aluminium are used.2. combination of emulsifiers: beeswax + divalent calcium ion

The viscosity of this type of creams prevent coalescence of the emulsified phases and helps in stabilizing the emulsionemulsified phases and helps in stabilizing the emulsion.Example:Cold cream: 6/27/2012 [email protected]

4. PREPARATION OF OINTMENTS BY EMULSIFICATION4. PREPARATION OF OINTMENTS BY EMULSIFICATION

Cold cream:Procedure:

1. Water immiscible components e.g. oils, fats, waxes are melted together over water bath (70C).melted together over water bath (70C).

2. Aqueous solution of all heat stable, water soluble components are heated (70C).

3. Aqueous solution is slowly added to the melted bases with continuous stirring until the product cools down and a semi-solid mass is obtained.semi solid mass is obtained.

1. N.B. The aqueous phase is heated otherwise high melting q p g gpoint fats and waxes will immediately solidify on addition of cold aqueous solution.


End Of Part 2

Preparation Of Ointments

Part 3Stability Of OintmentsStability Of Ointments


STABILITY OF OINTMENTSSTABILITY OF OINTMENTS

The ointments should remain stable from the time of preparation to the time when the whole of it is consumed by the user.the user.

(i) To stop microbial growth preservatives are added. ( ) p g pPreservatives for ointment includes : p-hydroxy benzoates, phenol, benzoic acid, sorbic acid, methyl paraben, propylparaben quaternary ammonium compounds mercury paraben, quaternary ammonium compounds, mercury compounds etc.

(ii) The preservatives should not react with any of the component of the formulation. Plastic containers may absorb the preservative and thereby decreasing the concentration of the preservative and thereby decreasing the concentration of preservative available for killing the bacteria.


STABILITY OF OINTMENTSSTABILITY OF OINTMENTS

(iii) Some ingredients like wool fat and wool alcohols are susceptible to oxidation. Therefore, a suitable antioxidant may be incorporated to protect the active ingredients from be incorporated to protect the active ingredients from oxidation.(iv) Incompatible drugs, emulsifying agents and preservatives must be avoided. The drugs which are likely to hydrolyze must be dispensed in an anhydrous base.(v) Humectants such as glycerin propylene glycol and (v) Humectants such as, glycerin, propylene glycol and sorbitol may be added to prevent the loss of moisture from the preparation.(vi) Ointment must be stored at an optimum temperature otherwise separation of phases may take place in the emulsified products which may be very difficult to remix to p y yget a uniform product.


PASTEPASTE

Syllabus:Differences between ointments and pastesDifferences between ointments and pastes.Bases of pastesPreparation of paste and their preservation.p p p


PASTEPASTE

Differences between pastes and ointments;

P ll i l (50%) f fi l Pastes generally contains a large amount (50%) of finely powdered solids. So they are often stiffer than ointments.

When applied to the skin pastes adhere well, forming a thick coating protects and soothes inflamed and raw surfaces and

h d d b h h d minimizes the damage done by scratching in itchy conditions such as chronic eczema. it is comparatively easy to confine pastes to the diseased it is comparatively easy to confine pastes to the diseased areas whereas ointments, which are usually less viscous, tend to spread on to healthy skin, and this may result in sensitivity

ti if th ti t i f l di t reactions if the preparations contain a powerful medicament such as dithranol.


PASTEPASTE

Differences between pastes and ointments;

B f h d h Because of the powder contents pastes are porous; hence, perspiration can escape. Since the powders absorbs exudate, pastes with hydrocarbon base are less macerating than p y gointments with a similar base.

Th l h b h ff They are less greasy than ointments but since their efficacy depends on maintaining a thick surface layer they are far from attractive cosmetically.y

Most of the pastes are unsuitable for treating scalp conditions because they are difficult to remove from the hair.


JELLIESJELLIES

Definition: Jellies are transparent or translucent, non-greasy, semisolid preparation generally applied externally. They are used for medication, lubrication and some miscellaneous applications.Types of jellies:

1 Medicated jellies1. Medicated jellies(i) Water soluble drugs like local anaesthetics, spermicidesand antiseptics are suitable for incorporation in the jellies.(ii) They are easy to apply and evaporation of the water content produces a pleasant cooling effect. The medicinal film usually adheres well and gives protection but is easily removed by washing when the treatment is complete.e.g. ephedrine sulfate jelly - used to arrest bleeding from nose.pramoxine HCl a local anaesthetic - relieves discomfort of pruritispramoxine HCl , a local anaesthetic - relieves discomfort of pruritisand haemorrhoids.phenylmercuric nitrate - as spermicidal contraceptive6/27/2012 [email protected]

JELLIESJELLIES

2. Lubricant jelly

C h i f l di i i h Catheters, items of eletrodiagnostic equipment, such as cystoscopes, and rubber gloves or finger stalls used for rectal and other examinations require lubrication before use.q

The lubricants must be sterile for articles inserted into l f h b d h bl ddsterile regions of the body, such as urinary bladder.

For painful investigations a local anaesthetic may be included For painful investigations a local anaesthetic may be included as in Lignocaine Gel B.P.C.


JELLIESJELLIES

The following are more specialized jellies -(a) Patch testingHere the jelly is the vehicle for allergens applied to the skin to j y g ppdetect sensitivity.

Several allergens may be applied on one person Several allergens may be applied on one person.

The viscosity of the jelly and it leaves on drying help to keep the ti l tparticles separate.

(b) Electrocardiographyto reduce electrical resistance between the patients skin and electrodes of the cardiograph, an electrode jelly may be applied. This contains NaCl to provide good conductivity and often pumice powder which, when applied onto the skin, removes part of the horny layer of the epidermis, the main layer of electrical resistance.


JELLIESJELLIES

The following are more specialized jellies –

(b) El t di h(b) Electrocardiography

To reduce electrical resistance between the patients skin and To reduce electrical resistance between the patients skin and electrodes of the cardiograph, an electrode jelly may be applied.

This contains NaCl to provide good conductivity and often pumice powder which when applied onto the skin removes pumice powder which, when applied onto the skin, removes part of the horny layer of the epidermis, the main layer of electrical resistance.


JELLIESJELLIES

FORMULATIONPharmaceutical jellies are usually prepared by adding a thickening agent such as tragacanth or carboxythickening agent such as tragacanth or carboxymethylcellulose (CMC) to an aqueous solution in which drug has been dissolved.

The mass is triturated in a mortar until a uniform product is obtainedobtained.

For the preparation of jellies whole gum is preferred rather For the preparation of jellies whole gum is preferred rather than powdered gum because the former gives a clear preparation of uniform consistency.


JELLIESJELLIES

Th f ll ll d f h f llThe following gelling agents are used for the preparation of jellies.(i) Tragacanththe main hydrophilic component of tragacanth that gels in water h b d b i h h j lli i has been named bassorin - hence, tragacanth jellies are sometimes called bassorin paste.The amount of gum required for a preparation varies with its use:

) F l b i ti j ll 2 t 3%a) For lubricating jelly 2 to 3%.b) For dermatological vehicles about 5%.c) For incorporation of ichthamol, resorcinol, salicylic acid and

other medicaments about 5% is generally used All formulations other medicaments, about 5% is generally used. All formulations contain alcohol and/or glycerol and/or a volatile oil to disperse the gum and prevent lumpiness when water is added.

d) They vary in viscosity, due to the natural origin of the gum and d) They vary in viscosity, due to the natural origin of the gum and variations in milling and storage.

e) The film left on the skin tends to flake.f) Viscosity is rapidly lost outside the pH range of 4.5 to 7.0; for ) y p y p g ;

example if benzoic acid is used as the preservative.g) They are susceptible to microbial growth.


JELLIESJELLIES

The following gelling agents are used for the preparation of jellies.

2. Sodium alginateUses:- As lubricant - 1.5 to 2 % is used.Uses: As lubricant 1.5 to 2 % is used.As dermatological vehicle - 5 to 10 % is used.A trace of Ca - salt (CaCl2) may be added to increase the viscosity and most formulations contain glycerol as a dispersing agent.Advantage: Sodium alginate has an advantage over tragacanthAdvantage: Sodium alginate has an advantage over tragacanththat is available in several grade or standardized viscosity.


JELLIESJELLIES

The following gelling agents are used for the preparation of jellies.

3 Pectin3. PectinPectin is a very good gelling agent and is used in the preparation of many types of jellies including edible jellies.p p y yp j g jGlycerin is used as a dispersing agent and humectant in dermatological jellies.J ll b k d ll l d b h Jellies must be packed in well-closed containers because they lose water rapidly by evaporation and this lose water rapidly by evaporation and this is increased by the susceptibility of y p y p ypectin gels to syneresis (i.e. exudation of the aqueous phase as a result of contraction of the gel).


JELLIESJELLIES

The following gelling agents are used for the preparation of jellies.4. Starch

Starch in combination with gelatin and glycerin is commonly used Starch in combination with gelatin and glycerin is commonly used for preparations of jellies.Glycerin in 50% may act as preservative.Medicaments are incorporated in the cold jelly by trituration.

5. GelatinInsoluble in cold water but swell and softens in it It is soluble in Insoluble in cold water but swell and softens in it. It is soluble in hot water.Hot solution contain 2% gelatin forms a jelly on cooling.Very stiff (15%) jellies are melted before used and after cooling to desired temperature are applied with a brush to the affected area. The area is covered with bandage and the dressing may be left in The area is covered with bandage and the dressing may be left in place for several weeks.


JELLIESJELLIES

6. Cellulose derivativeMethyl cellulose and sodium carboxy methyl cellulose1 produce neutral jellies of stable viscosity1. produce neutral jellies of stable viscosity.2. Have good resistance against microbial growth.3. Clear due to freedom from insoluble impurities.4. Produce strong film after drying on the skin.Use: Sodium carboxy methyl cellulose can be used to prepare lubricating jellies and sterile jelliesprepare lubricating jellies and sterile jellies.e.g. lignocine gel - because it can withstand autoclaving temperature.N.B. Other cellulose derivatives areHydroxy propyl methyl cellulose (Hypermellose)CarbomerCarbomerPolyvinyl alcohols.


JELLIESJELLIES

7. Clays

G l i i 7 20 % f b i b d Gels containing 7 to 20 % of bentonite can be used as dermatological bases.

Disadvantages:1. They are opalescent and lack attractiveness.2. Their pH is about 9.0 i.e. not suitable for application on the skin.3 R id h ki i d d h ilk3. Residue on the skin is powdery and rather silky.


POULTICEPOULTICE

Definition: Poultice are paste-like preparations used externally to reduce inflammation because they retain heat well. After heating, the preparation is spread thickly on a dressing and applied, as hot as the patient can bear it, to the affected area.Uses;Uses;(i) Glycerol, because of its hygroscopic nature, is believed to draw infected materials from the tissues when the poultice is used for boils and similar infectionsused for boils and similar infections.(ii) Methyl salicylate (an antirheumatic drug),thymol (a powerful bactericide),boric acid (a weak antimicrobial agent),and peppermint oil (which contributes to the smell) are used for different purposesused for different purposes.


POULTICEPOULTICEM h d f l h lMethod of applying the poultice:-

1. For use, the poultice is heated, with occasional stirring, until it can only be tolerated on the back of the hand.tolerated on the back of the hand.

2. Then it is spread thickly on lint or other dressing and applied to the affected area which is sometimes first covered with muslin to facilitate removal after use.

3 A thi k l f tt l i li d t t i th h t d i f 3. A thick layer of cotton wool is applied to retain the heat and a covering of oiled silk may be added to protect clothing.

Example:pThe only example given in the pharmacopoeia is Kaolin Poultice B.P.C.Formula: Heavy kaolin, finely sifted and dried at 100C 52.7 gBoric acid, finely sifted 4.5 gMethyl salicylate 0.2 mlThymol 50 mgPeppermint oil 0.05 mlGlycerin 42.5 g


6/27/2012 [email protected] 75

SUPPOSITORY:SUPPOSITORY:

It is a small solid medicated mass, usually cone-shaped ,that is inserted either into the rectum (rectal suppository), vagina (vaginal ( pp y) g ( gsuppository or pessaries) where it melts at body temperature .

SUPPOSITORYSUPPOSITORY

Types of suppositories, Suppository bases, classification, properties, preparation and packaging p p p p p g gof suppositories.

Use of suppositories for drug absorption.



Definition:

S i i i ll h d lid d f f Suppositories are specially shaped solid dosage form of medicament for insertion into body cavities other than mouth.

They may be inserted into rectum, vagina or the urethra.

This products are so formulated that after insertion, they will either melt or dissolve in the cavity fluids to release the either melt or dissolve in the cavity fluids to release the medicament.



Advantages of rectal suppositories:1. Mechanical action: The rectal suppositories are extensively used

as a mechanical aid to bowel evacuation which produce its action by either irritating the mucous membrane of the rectum (e.g. glycerol and bisacodyl) or by lubricating action or by mechanical lubrication.

2. Local action: The rectal suppositories may be used for soothing, antiseptic, local anaesthetic action or for astringent effect. Therefore, they may contain soothing e.g. zinc oxide, local

th ti i h i b i t i t bi th anaesthetic- e.g. cinchocaine, benzocaine, astringents e.g. bismuth subgallate, hamamelis extract and tannic acid antiinflammatorye.g. hydrocortisone and its acetate.

3 T id t i ti S it i i t d 3. To provide systemic action: Suppositories are convenient mode of administration of drugs which irritate the gastrointestinal tract, cause vomiting, are destroyed by the hepatic circulation, or are destroyed in the stomach by pH changes enzymes etcdestroyed in the stomach by pH changes, enzymes etc.



Partial bypass: The lower portion of the rectum affords a large absorption surface area from which the soluble substances can absorb and reach the systemic circulation.e.g. aminophylline used in asthmatic and chronic bronchitis.morphine a powerful analgesicergotamine tartarate used to treat migraineg gindomethacin and phenyl butazone analgesic and antiinflammatoryactions.Systemic treatment by the rectal route is of particular Systemic treatment by the rectal route is of particular value for(a) treating patients who are unconscious, mentally disturbed or unable to tolerate oral medication because of vomiting or unable to tolerate oral medication because of vomiting or pathological conditions of the alimentary tract.(b) administering drugs, such as aminophylline, that cause gastric irritation andirritation, and(c) treating infants.


PESSARIESPESSARIESPessaries are solid medicated preparations for introducing into the vagina, where they melt or dissolve and exert a local action.action.They are used mainly for vaginitis (inflammation of the vagina) and leucorrhoea (unpleasant vaginal discharge). Vaginitis may be caused by a variety of micro-organisms or key old age. The medicaments in official pessaries are:

1 acetarsol an antiprotozoal agent1. acetarsol an antiprotozoal agent2. di-iodohydroxyquinoline for yeast and protoplast infections.3. lactic acid often useful in leucorrhoea4. nystatin for yeast infections5. crystal violet for various microbial infections.


PESSARIESPESSARIESTYPES OF SUPPOSITORIES:1. Rectal suppositoriesTh f i d i i h f h i These are meant for introduction into the rectum for their systemic effect. They are tapered at one or both ends and usually weigh about 2 gm. The rectal suppositories meant for y g g ppchildren are smaller in size and weight is 1 gm.2. Vaginal suppositories:Th f d They are meant for introduction into vagina.They are larger than rectal suppositories and vary in weight from 3 to 6 gm or more.from 3 to 6 gm or more.They may be conical, rod-shaped or wedge shaped.They a re exclusively used for their local action on vagina.y y g


PESSARIESPESSARIESTYPES OF SUPPOSITORIES:3. Urethral Suppositories (or Urethral bougies)Th f i d i i h hThey are meant for introduction into the urethra.Their weight varies from 2 to 4 gm and length from 2 to 5 inch. Urethral suppositories are very rarely used.inch. Urethral suppositories are very rarely used.

4. Nasal suppositories (Nasal bougies)They are meant for introduction into nasal cavity.They are similar in shape to urethral bougies.Their weight is about 1 gm and length 9-10 cm.They are always prepared with glycero-gelatin base.


PESSARIESPESSARIESTYPES OF SUPPOSITORIES:

5 E ( i i )5. Ear cones (aurinaria)

They are meant for information into the earThey are meant for information into the ear.Generally theobroma oil is used as a base.They are prepared in an urethral bougies mould and cut y p p gaccording to the required size.


PESSARIESPESSARIESProperties of an Ideal Suppositories Base

1. It should melt at body temperature or dissolve or disperse in body fluids.y

2. It should release any medicament readily.3. It should keep its shape when being handled.4. It should be non-toxic and non-irritant to the mucous

membrane.5. It should be stable on storage.g6. It should be compatible with any added medicament.7. It should be stable if heated above its melting point.8. It should be easily moulded and should not adhere to the

mould.9. It should be easily mouldable by pouring or cold y y p g

compression.


PESSARIESPESSARIES1. Since it is not possible to get all the above mentioned

qualities in a single base, so a combination of bases is used to get a product of required qualities. to get a product of required qualities.

2. A number of patent “improved” suppository bases are p p pp yavailable. Most of these are mixtures of fats, waxes and/or esters in specific proportions according to the desired qualities of the product to be obtained qualities of the product to be obtained.

3. Glycerogelatin and polyethylene glycols are being widely y g p y y g y g yused as suppository bases, though theobroma oil is extensively used in extemporaneous preparations but it is losing its importance because it is unstable to heat and has losing its importance because it is unstable to heat and has undesirable physical properties.


PESSARIESPESSARIESTypes of Suppository Bases

1 F b h l b d 1. Fatty bases - these melt at body temperature.2. Water-soluble or water miscible bases - these dissolve or disperse in rectal secretions.disperse in rectal secretions.3. Emulsifying bases


PESSARIESPESSARIESFATTY BASESTheobroma oil (Cocoa butter)I i ll i h hi lid i h h l lik d I i It is a yellowish-white solid with a chocolate-like odour. It is a mixture of glyceryl esters of stearic, palmitic, oleic and other fatty acids. Its valuable characteristics include -yAdvantages:(a) A melting point range of 30 to 36 0C; hence it is solid at

l b l h b dnormal room temperatures but melts in the body.(b) Ready liquefaction on warming and rapid setting on cooling.cooling.(c) Miscibility with many ingredients.(d) Blandness i.e. does not produce irritation( ) p


PESSARIESPESSARIESFATTY BASESDisadvantages:(a) Polymorphism(a) PolymorphismWhen melted and cooled it solidifies in different crystalline forms, depending on the temperature of melting, rate of

li d i f th cooling and size of the mass. If melted at not more than 360C and slowly cooled it forms stable beta crystals with normal melting point, but if over-heated it may produce, on cooling, unstable gamma crystals, which melt at about 150C, or a-crystals, melting at about 200C. These unstable forms eventually return to the stable condition but this may take several days and meanwhile, the suppositories may not set at room temperature or, if set by suppositories may not set at room temperature or, if set by cooling, may remelt in the warmth of the patient’s home.


PESSARIESPESSARIES(b) Adherence to mouldBecause theobroma oil doesn’t contract enough on cooling to loosen the suppositories in the mould, sticking may occur, particularly if the mould is worn. This is prevented by lubricating the mould before use.

(c) Softening point too low for hot climatesTo raise the softening point, whit beeswax may be added to theobroma oil suppositories intended for use in tropical and pp psubtropical countries.

(d) Melting point reduced by soluble ingredients(d) Melting point reduced by soluble ingredientsSubstances, such as chloral hydrate, that dissolve in theobroma oil, may lower its melting point to such an extent that the suppositories are too soft for use To restore the melting point a suppositories are too soft for use. To restore the melting point, a controlled amount of white beeswax may be added.


PESSARIESPESSARIES(e) Slow deterioration during storageThis is due to oxidation of the unsaturated glycerides.

(f) Poor water absorbing capacityThis fault can be improved by the addition of emulsifying agents.

(g) Leakage from the body(g) Leakage from the bodySometimes melted base escapes from the rectum or vagina. This is most troublesome with pessaries because of their l i d th f th l d ith larger size, and therefore, these are rarely made with theobroma oil.

(h) Relatively high cost


PESSARIESPESSARIESSynthetic fatsAs a substitute of theobroma oil a number of hydrogenated oils, e.g. hydrogenated edible oil, arachis oil, coconut oil, palm , g y g , , , pkernel oil, stearic and a mixture of oleic and stearic acids are recommended.

N.B. Synthetic suppositories bases are by hydrogenation and subsequent heat treatment of vegetable oils such as palm oil

d hi il and arachis oil.

The oils are generally esters of unsaturated fatty acids. g y yHydrogenation saturates the unsaturated fatty acids and heat treatment splits some of the triglycerides into fatty acids and partial esters (mono- and di-glycerides).partial esters (mono and di glycerides).


PESSARIESPESSARIESAdvantages of these synthetic fats over theobroma oil:

1. Their solidifying points are unaffected by overheating.2 They have good resistance to oxidation because their 2. They have good resistance to oxidation because their unsaturated fatty acids have been reduced.3. Their emulsifying and water absorbing capacities are good. [They usually contain a proportion of partial glycerides some of which, e.g. glyceryl monostearate, are w/o emulsifying agents and, therefore, their emulsifying and water absorbing agents and, therefore, their emulsifying and water absorbing capacity are good.4. No mould lubricant is required because they contract significantly on cooling.5. They produce colorless, odourless and elegant suppositoriessuppositories.


PESSARIESPESSARIESDisadvantages:

1 Th h ld b l d i f i b h 1. They should not be cooled in refrigerator because they become brittle if cooled quickly. Certain additives e.g. 0.05 % polysorbate80, help to correct this fault.p y p

2. They are more fluid than theobroma oil when melted and h d Th k h at this stage sedimentation rate is greater. Thickeners such as

magnesium stearate , bentonite and colloidal silicon dioxide, may be added to reduce this.y


PESSARIESPESSARIESWATER SOLUBLE AND WATER MISCIBLE BASESGlycero-Gelatin baseThi i i f l l d d i iff j ll This is a mixture of glycerol and water made into a stiff jelly by adding gelatin.It is used for the preparation of jellies, suppositories and It is used for the preparation of jellies, suppositories and pessaries. The stiffness of the mass depends upon the proportion of gelatin used which is adjusted according to its useuse.The base being hydrophilic in nature, slowly dissolves in the aqueous secretions and provide a slow continuous release of q pmedicament. Glycerogelatin base is well suited for suppositories containing belladonna extract, boric acid, chloral hydrate bromides iodides iodoform opium etcchloral hydrate, bromides, iodides, iodoform, opium, etc.


PESSARIESPESSARIESWATER SOLUBLE AND WATER MISCIBLE BASESGlycero-Gelatin base· Depending upon the compatibility of the drugs used a Depending upon the compatibility of the drugs used a suitable type of gelatin is selected for the purpose. Two types of gelatins are used as suppository base

(i) Type-A or Pharmagel-A which is made by acid hydrolysis (has isoelectric point between 7 to 9 and on the acid side of the range behaves as a cationic agent, being most effective at pH 7 to 8. ) is used for acidic drugs.

(ii) Type-B or Pharmagel-B which is prepared by alkaline hydrolysis (having an isoelectric point between 4.7 to 5 and on the alkaline side of the range behaves as an anionic agent on the alkaline side of the range behaves as an anionic agent, being most effective at pH 7 to 8 ) is used for alkaline drugs


PESSARIESPESSARIESSoap-Glycerin SuppositoriesIn this case gelatin and curd soap or sodium stearate which makes the glycerin sufficiently hard for suppositories and a makes the glycerin sufficiently hard for suppositories and a large quantity of glycerin upto 95% of the mass can be incorporated.

Further the soap helps in the evacuation of glycerin.

The soap glycerin suppositories have the disadvantage that they are very hygroscopic, therefore they must be protected they are very hygroscopic, therefore they must be protected from atmosphere and wrapped in waxed paper or tin foil.

Polyethylene glycol bases / Macrogol bases (Carbowaxes)


PESSARIESPESSARIESEMULSIFYING BASESThese are synthetic bases and a number of proprietary bases of very good quality are available, few of which are described below:very good quality are available, few of which are described below:WitepsolThey consist of triglycerides of saturated vegetable acids (chain length C12 to C18) with varying proportions of partial esters.Massa EsteriumThis is another range of bases consisting of a mixture of di- tri-This is another range of bases, consisting of a mixture of di , triand mono- glycerides of saturated fatty acids with chain lengths of C11 to C17.M lMassuppolIt consists of glyceryl esters mainly of lauric acid, to which a small amount of glyceryl monostearate has been added to improve its water absorbing capacity.


PESSARIESPESSARIESPREPARATION OF SUPPOSITORIESSuppositories are prepared by two processes: moulding (hot process or fusion process) and cold compression.p p ) pMouldVarious types and sizes of suppository moulds are available. In the dispensary suppository moulds with six or twelve cavities with desired shape and size may be used. For large scale production moulds up to 500 cavities may be used.Moulds are made up of stainless steel, nickel-copper alloy, brass, aluminium or plastic.For cleaning lubrication and removal of suppositories the For cleaning, lubrication and removal of suppositories the mould can be opened longitudinally by removing the screw in the centre of the plates.Th i l iti f th ld 1 2 4 The nominal capacities of the common moulds are 1g, 2g, 4g and 8g.


PESSARIESPESSARIESC lib i f h ldCalibration of the mouldThe nominal capacity of a mould is not always correct. It will vary for different bases. Each mould should be calibrated before use by preparing a set of suppositories or pessaries using the base alone preparing a set of suppositories or pessaries using the base alone, weighing the products and taking the mean weight as the true capacity. This is repeated for each base and the value is recorded for future use.Displacement valueThe volume of a suppository from a particular mould is uniform but its weight will vary because the densities of medicaments

ll diff f h d i f h b i h hi h h ld usually differ from the density of the base with which the mould was calibrated.To prepare products accurately, allowance must be made for the change in density of the mass due to added medicaments For this change in density of the mass due to added medicaments. For this purpose the displacement value of a medicament is taken into consideration.Definition: The number of parts of medicament (drug) that p ( g)displaces one part by weight of the base is known as the displacement value of that drug.


THE ENDTHE END


Semisolid Dosage Forms by BIBEK SINGH MAHAT

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Transcript of Semisolid Dosage Forms by BIBEK SINGH MAHAT