dr. rer. nat. rebaz h. ali - · pdf filedr. rer. nat. rebaz h. ali . ... • pharmaceutical...

University of Sulaimani School of Pharmacy Dept. of Pharmaceutics 1st semester

Dr. rer. nat. Rebaz H. Ali

1/10/2017 Pharmaceutical Compounding 2

Outlines

• Introduction

• Clarification

• Water

• Aromatic water

• Syrups


Introduction

• Pharmaceutical necessities or adjuvants, are substance which added to improve the

“elegance” of the product.

• Pharmaceutical formulation is said to be “elegant” if it meets three standards of

quality. It should be

• Stable

• Palatable

• Therapeutically effective.

• Syrups and Aromatic waters are designed to provide a base which will produce

palatable medicinal products.


Shelf-life

• Stability is the extent to which a product retains within specified limits and throughout

its period of storage and use (i.e., its shelf life) the same properties and characteristics

that it possessed at the time of its manufacture.

• Five types of stability concern pharmacists:

1. Chemical: Each active ingredient retains its chemical integrity and labeled potency

within the specified limits.

2. Physical: The original physical properties, including appearance, uniformity, and

etc.

3. Microbiological

4. Therapeutic

5. Toxicological


Shelf-life

• Shelf life: may be defined as the time required for the drug level in a product stored at

room temperature (normally 25 oC) to degrade to 90 % of its labeled potency.

• Chemical changes which may be observed include hydrolytic degradation and auto-

oxidation (temperature, light, and humidity)

• Physical changes include precipitation and alteration in color, odor and viscosity.


Outlines

• Introduction

• Clarification

• Clarification methods

• Settling

• Filtration

• Water

• Aromatic water

• Syrups


Clarification

• Clarification is an operation which involves the removal of suspended matter from a

fluid medium.

• In pharmaceutical processing there are two main reasons for such processes:

• to remove unwanted solid particles from either a liquid product or from air

• to collect the solid as the product itself (e.g. following crystallization).

• The specific procedures and equipment which may be used to achieve clarification are

dependent on:

• The particle size of the suspended matter.

• The physical state of the suspended matter.

• The quantity of suspended matter.

• The characteristics of the fluid medium.

• The speed of the operation.


Settling

• The simplest method of clarification is to allow the liquid to stand in a suitable

container until the suspended matter either has settled or has risen to the top of the

liquid.

• The insoluble matter may be separated from the clear liquid phase by skimming,

decantation, or siphoning.

Skimming Decantation Siphoning


Settling cont.

• Settling process fails if

• The suspended matter is colloidal

• The density of the suspended particles is approximately equal to that of liquid

phase.

• Acceleration of the settling process can be accomplished by centrifugation.


Filtration or straining

• Filtration is the process of removing solid particles from a fluid by passing the

suspension through porous, fibrous, or granular substances.

• A filter or strainer is a surface upon which solids are deposited.

• It consists essentially of a medium which contains numerous pores which may

vary in size and shape and may be characterized by a high degree of tortuosity.

• They cats by impeding the passage of suspended particles with diameters greater

than that of the pores, while allowing the liquid to pass.


Filtration or straining cont.

• Ultra-filters are filters which are retentive to colloidal matter.

• The rate of filtration, is the volume of liquid passed, through the filter per unit time.

• Rate of filtration =(𝑓𝑖𝑙𝑒𝑟 𝑎𝑟𝑒𝑎)∗(𝑑𝑟𝑜𝑝 𝑝𝑟𝑒𝑠𝑠𝑢𝑟𝑒)

𝑙𝑖𝑞𝑢𝑖𝑑 𝑣𝑖𝑠𝑐𝑜𝑠𝑖𝑡𝑦 ∗(𝑓𝑖𝑙𝑡𝑒𝑟 𝑟𝑒𝑠𝑖𝑠𝑡𝑎𝑛𝑐𝑒)



• Pressure drop is neglected if:

• Highly retentive filters are used.

• Highly viscous liquids such as syrup are being filtered

• Suction filtration increases the pressure drop by lowering the pressure beneath the

filter.



• Properties of filter media

• Capable of delivering a clear filtrate at suitable production rate.

• It must withstand mechanical stresses without rupturing.

• No chemical or physical interactions with the components of the filtrate should

occur.



• Types of filter media

• Sheet of woven material: like cotton, wool, synthetic material such as nylon and

filter paper.

• Unwoven fibrous materials: like cotton and asbestos fibers.

• Porous plate: natural porous materials, like stone, porcelain and other ceramics.

• Membrane filters: like Millipore filters.

• Granular or powdered materials: like sand, charcoal, etc.


Filter aids

• Filter aids: They a fine surface deposit that screens out all

solids, preventing them from contacting and plugging the

filter medium.

• Mechanism of action:

• They form a layer of second medium which protects the

basic medium (precoat).

• They improve the flow rate by decreasing cake

compressibility and increasing cake permeability (admix).

• E.g. silica, aluminosilicate, cellulose, talc and carbon.

• Properties of filter aids: they should be inert, irregular,

insoluble, incompressible

Filter aid

Filter medium


Outlines

• Introduction

• Clarification

• Water

• Purification methods

• Aromatic water

• Syrups


Water

1. Water, U.S.P.: it can be used:

• In the washing and the extraction of crude drugs.

• In the preparation of products for external use.

Water can be divided into two general types:

1. Bulk water, which are typically produced on site where they are used.

2. Packaged water, which are produced, packaged and sterilized to preserve microbial

quality throughout their packaged shelf life.

• A 100 mL portion of official water contains not more than 100 mg of residue after

evaporation.

• These dissolved solids consist of the chlorides, the sulfate and the bicarbonates of

sodium, potassium, calcium and magnesium.


Water cont.

2. Purified water U.S.P.: Is used in the preparation of all medication containing water

except ampoules, injections.

• A 100 mL portion of official water contains not more than 1 mg of residue after

evaporation.

A. Distillation

• Distillation is a process that involves the

evaporation of water and then the condensation

of the resulting steam.

• It allows the removal of almost all of the organic

and inorganic impurities and achieves very-high-

quality water.

• It is also considered the safe way to avoid

microbial and endotoxin contamination.


Water cont.

B. ion-exchange

• An Ion-exchange resin is the beads that are typically porous (providing a high surface

area) and are insoluble in water.

• It is based on the ability of the resins to selectively adsorb either cations or anions,

and to release other ions based on their relative activity; thus the process is called

Ion-exchange.

• They are cationic (sulfonic acid and carboxylic acid) and anionic (amino).


Water cont.

• Advantages

• Elimination of the use of heat.

• Simpler equipment.

• Lower costs.

• Ease of production and storage.

• Water softening is the replacing of Mg++ and Ca++ ions found in hard

water with Na+ ions.


Water cont.

3. Water for injection, U.S.P. this is a pyrogen-free water, purified by distillation, for the

preparation of products for parenteral use, it should prepared under aseptic condition.

• Pyrogens are fever-producing substances probably of bacterial origin; they probably

consist of polysaccharide-bearing antigens.

Heating at 250 oC for 30 minutes

Not more than 0.5o C


Water cont.

4. Sterile water for injection U.S.P., it is prepared from water for injection that is

sterilized and suitably packaged.

• It contains no antimicrobial agent or other added substance.

• It is not suitable for intravascular injection without its first having been made

approximately isotonic by the addition of a suitable solute.

• It is used for the reconstitution of other parenteral products, in most cases

antibiotics.

• Sterilization is the freeing of materials from all living organisms and

their spores.

• Methods of sterilization

1. Autoclave

2. Boiling the distilled water for at least 60 minutes in a tightly

closed flask


Water cont.

5. Bacteriostatic water for injection, U.S.P., it is prepared from water for injection that is

sterilized and suitably packaged.

• Containing one or more suitable antimicrobial agents.

• Typically is used for Multi-dose products that require repeated content withdrawal.

• It is contraindicated in newborns.


Outlines

• Introduction

• Clarification

• Water

• Aromatic water

• Methods for preparation of aromatic water

• Stability

• Syrups


Aromatic water

• These are aqueous solutions, usually saturated volatile substances characterized by very

low water-solubility.

• It’s providing a pleasantly flavored medium for the administration of water-soluble

drugs, and for liquid phase of emulsion and suspension.

• Examples

• Aromatic waters prepared from essential oils, like peppermint water, have been

used as carminative and antispasmodic.

• Rose water is a perfume

• Hamamelis water was used as a rub, astringent, perfume in aftershave lotions.

• Essential oil consists of hydrocarbon part called terpene (water-insoluble) and aromatic

carrier part (water-soluble)


Methods for preparation of aromatic water according to USP

1. Distillation: the odoriferous portion of the plant is added into a distillator with

sufficient purified water and then distilling most of the water.

• The excess oil is separated form the distillate.

• E.g. Rose Water, Orange Flower Water and Hamamelis Water

2. Solution

• The volatile substance is agitated with purified water for a period of time. The

mixture is then set aside for at least 12 hours, to ensure saturation, before it is

filtered through wetted filter paper.

• This method is simpler, quicker and more economical.

• E.g. chloroform water which is used as expectorant.

• When it is dispensed, the bottle should not be shaken, and only the

supernatant liquid should be used

• What will happen if you drink chloroform?


Methods for preparation of aromatic water according to USP cont.

3. Alternate solution

• Volatile substance + talc powder + purified water → mix for 10 min → filtration.

• Talc acts as distributing agent that accelerates the rate of solution by facilitating the

breaking up of the aromatic substance into fine particles.

• Some time surface active agent like polysorbate 80 (tween 80) can be used for

preparation of aromatic water.

• Disadvantage

• they foam excessively on agitation

• develop a disagreeable taste

• more easily subject to mold growth.


Stability

• Many waters support the growth of molds.

• The solutes are volatile materials, loss of aroma occurs on prolonged exposure to

elevated temperature. While lowering the temperature causes separation of the

aromatic component, thus producing cloudiness.

• The insoluble material may collect on the top of the liquid imparting the burning taste of

the first dose.

• Many of aroma-bearing solutes are oxidizable compounds and auto-oxidation can be

catalyzed by light.

• Chloroform water should be stored in light resistant bottle since light catalyze the

oxidation of chloroform to the poisonous gas (phosgene).

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