COSMETIC PREPARATIONS: Various Facial cream

 INTRODUCTION TO FACIAL COSMETICS

Part 1: Introduction, Types of facial cream

Link for video demonstration of this topic 👇👇

https://youtu.be/J8B0J3c-_wQ

https://youtu.be/9hk4xOxLAHs

Cosmetic is a Greek word which means to 'adorn' (addition of something decorative to a person or a thing). It may be defined as a substance which comes in contact with various parts of the human body like skin, hair, nail, lips, teeth, and mucous membranes etc, Cosmetic substances help in improving or changing the outward show of the body and also masks the odour of the body. It protects the skin and keeps it in good condition. In general, cosmetics are external preparations which are applied on the external parts the body. 

Facial Makeup Products are products that are used to color and highlight facial features. They can either directly add or alter color or can be applied over a foundation that serves to make the color even and smooth.

Various Facial Cosmetics are:

• Cream
• Eye makeup preparations
• Shaving preparations

CREAM

Creams are semi-solid emulsions which contain mixtures of oil and water. Their consistency varies between liquids and solids.

Creams are classified according to their functions. They are: 

• Cleansing creams
• Cold Creams. 
• Foundation and vanishing Creams. 
• Night and Massage Creams. 
• Hand and Body Creams.
• Moisturising cream
• All-purpose Creams 

CLEANSING CREAM:

They are used for the purpose of removing makeup, surface grime (layer of dirt on skin) and secretions of skin from the face respectively. 

Properties: 

• They are easy to apply. 
• They spread easily on the skin. 
• They are pleasant in appearance. 
• They cause less irritation to the skin. 

• They should melt or liquefy when applied on to the skin.
• They should produce flushing action on skin and its pore openings. 
• They should form an emollient film on the skin after application. 
• They should not make skin dry which happens in case, when the skin is washed with water and soap. 
• They should remove chemicals of facial makeup effectively. 
• They should remove solidified oil, sebum, sebum plaques and surface oil layer from the skin. 
• They also help in softening, lubricating and protecting skin apart from cleansing purposes.

Cleansing creams are of two types. They are: 

1. Bees wax-borax type / Emulsified type: It is an oil-in water type of emulsion, in which high percentage of mineral oil is present. This mineral oil helps in imparting cleansing property. It is white, lustrous and good consistency. 
2. Liquefying type: This type of creams consist of a mixture of oil and water which are translucent in nature. They are translucent in nature .they are anhydrous creams with thixotropic character i.e., they liquefy when applied on skin.

E.g. Of Formulation:

Bees wax-borax type / Emulsified type: 

Mineral oil, isopropyl myristate, acetoglyceride, petroleum jelly and bees wax heated to a temperature of about 75°C in a separate glass container (ingredients having least melting point are melted first and then high melting point ingredients are melted). This is mixture A.

In other glass container borax and water are heated to same temperature i.e., 75°C.preservatives are dissolved in water before heating. This is mixture B. 

Mixture B is added to the mixture A slowly, along with continuous stirring. Stirring carried out until a thick stable emulsion is formed. 

Perfume is added to the preparation when it attains a temperature of 35°C and stirring is carried out. 

Then the preparation is passed through a triple roller mill for milling purpose. 

Preparation is transferred and stored in a suitable container. 

Liquefying type: 

Mineral oil, petrolatum and ozokerite wax are heated together to a temperature of about 65°C (First ozokerite wax is melted followed by petrolatum and mineral oil). 

The above mixture is cooled along with continuous stirring. 

Preservative and perfume are added to the mixture after it attains a temperature of 40° C. 

Then the preparation is transferred and stored in a  container.

COLD CREAM:

Cold cream is an emulsion of water and certain fats, usually including beeswax and various scent agents, designed to smooth skin and remove makeup. They produce cooling sensation by the evaporation of water, after application of cream to the skin. They should possess emollient action and the layer left on the skin after application should be  non-occlusive. 

E.g. Of Formulation:

Beeswax is melted in a container by using water bath to a temperature of about 70° C. 

Then mineral oil is added to the melted beeswax. This is mixture A. 

In another container, water is heated to a temperature of about 70° C and borax is dissolved in it. This is mixture B.

Mixture B (aqueous phase) is added slowly to mixture A (oily phase) along with stirring. Stirring is carried out until a creamy emulsion is formed. 

Finally, perfume is added to the preparation when it attains a temperature of about 40°C. 

VANISHING CREAM:

These creams are also referred to as 'Day Creams' as they are applied during day times. These creams provide emollient as well as protective action to the skin against environmental conditions by- forming a semi-occlusive residual-film. This film is neither greasy nor oily. They are oil in water type of emulsion. When applied on the surface of skin, they spread as thin oil less film which is not visible to the naked eye. Hence, they are called as vanishing creams. They are used to hold powder on the skin as well as to improve adhesion.

Ideal Properties are:

• It should have high melting point.

• It should be pure white in colour. 

• It should possess very little odour. 

• It should have less number of iodine.

Ingredients required:

• Main ingredient- E.g. stearic acid 
• Humectants- E.g. glycerin, sorbitol, propylene glycol 
• Alkali- E.g. 

(a) Potassium hydroxide- It imparts fine texture and consistency without providing harshness 

(b) Sodium hydroxide- It is used in combination with potassium hydroxide because it forms hard cream, when used alone. 

(c) Carbonates- They are widely used, because they carbon dioxide due to this, creams become spongy.

(d) Ammonia- It is effective, but difficult to handle because of odour and volatility. it is also make cream yellow in color with age. 

(e) Borax- It is used in combination with potassium hydroxide to produce a white emulsion. 

• Emulsifying agent- E.g. triethanolamine soap, Amino glycol soap or Glyceryl monostearate 
• Purified water (i.e., distilled and deionized)- It provides stability to the cream. If hard water is used, it leads to the formation of soaps of lime and magnesium, which causes inversion of emulsion and hence stability is reduced.
• Preservatives- E.g. methyl paraben and propyl paraben- They prevent deterioration cause by bacteria or fungi. 
• Perfume- E.g. geranium, sandal wood, lavender oil, terpineol etc- They should be added when the cream attains a temperature of about 40°c. It provides odour to the cream and also has aesthetic value.

E.g. of formula

Stearic acid is melted in a container by using water bath. 

Potassium hydroxide is dissolved in water and then glycerin is added. This mixture is heated to a temperature of about 75' C. This is aqueous phase. 

Slowly aqueous phase is added to melted stearic acid along with continuous stirring. 

Perfume is added to the preparation when it attains a temperature of 40° C.

FOUNDATION CREAM:

They provide emollient base or foundation to the skin. They are applied before applying face powder or other preparations of make-up. 

Ideal Properties are:

• Adhesion of powder to the skin is improved by these creams, as they possess good holding capacity. 

• They should be easily spread on the skin. 

• They should be non-greasy in nature. 

• They should be capable of leaving a non-occlusive film on the skin after application.

These are of two types: 

(i) Pigmented Foundation Creams: They are colored creams. 

(ii) Unpigmented Foundation creams: These creams do not contain pigments in the formulation.

Ingredients used:

• Humectant and lanolin- They cause retention of powder on the skin.
• Mineral oil- It improves powder adhesion to the skin.
• Isopropyl myristate, butyl stearate and ester- They also improves adhesion power due to their low surface tension property.
• Pigments like titanium dioxide, talc, calamine- They impart color.

E.g. of formula

Lanolin, cetyl alcohol, stearic acid and potassium hydroxide are heated to a temperature of about 75°C in one container. This is oily phase. 

In another container, water and propylene glycol are heated to same temperature i.e., 75°C. Preservatives should be dissolved in water before heating is carried out. This is aqueous phase. 

Then slowly aqueous phase is added to oily phase along with continuous stirring until the preparation becomes cold. 4. Perfume is added to the preparation when the above mixture reaches a temperature of 35°C. 

Finally the preparation is passed through a triple roller mill for milling purpose. 

NIGHT & MASSAGE CREAM

(a) Night Creams: The preparations which are applied during night time and removed in the morning are called night creams. 

(b) Massage Creams: The preparations which are gently applied and rubbed on the skin 

through massage technique are called massage creams. 

Ideal Properties are:

These creams are formulated with fatty substances which help in easy spreading on the skin. 

These creams help in providing occlusive layer to the skin, which reduce the rate of water loss from the transepidermal layer. The occlusive layer is also responsible for providing moisturizing effect on the skin. 

Ingredients used:

1. Water soluble ingredients: Example: Propylene glycol, Glycerol, sorbitol ETC.

They reduce evaporation of water in case of oil-in-water type of emulsion. The activity of retaining water in external Phase is known as emollient activity, which in turn provides water to stratum corneum. 

2. Fat soluble ingredients: Example: mineral oil, petroleum jelly, Paraffin, ceresin, dimethyl polysiloxanes, Methyl phenyl polysiloxanes etc. 

They help in reducing evaporation of water from the surface of the skin by forming a thin film. 

E.g. of formula

Mineral oil, petroleum jelly, white beeswax, paraffin wax and lanolin are heated to a temperature of about 75°C in a one container. This is mixture A. 

Borax, water and antioxidant are heated in another separate container to same temperature i.e. 75°C. Preservative is dissolved in water before heating the mixture. This is mixture B. 

Slowly mixture B is added to mixture A along with continuous stirring. 

Perfume is added after the preparation has attained a temperature of about 35°C. 

HAND & BODY CREAM

Due to exposure of skin to water, soaps and detergents many times a day, removal of lipids and other secretions from the skin occurs. Cold and dry winds are responsible for chapping of the skin. Chapping occurs due to loss of moisture from the skin, which is also associated with cracking. 

Hence, hand and body creams are formulated with suitable emollient, which not only make water available but also regulates the water take-up by the cells of stratum corneum.

Ideal Properties are:

• They are easy to apply. 

• They help in softening or imparting emollient effect to hands. 

• They should not leave behind sticky film after their application. 

• They should not interfere with perspiration of the skin as it may re bioavailability. 

• Perfume and colour should be added in the cream preparation for pleasant smell and appearance. 

Various ingredients used:

1. Humectants: Example: propylene glycol, glycerin and Sorbitol.- To prevent evaporation of water from the skin. 

2. (a) natural gums: Example: karaya, acacia, tragacanth, Agar-agar. 

Or (b) synthetic substances: Example : carboxy celluloses, polyvinyl alcohol- They form occlusive film on the skin, which inturn prevent evaporation of water. 

3. Emollients: Example: mineral oil, waxes and lanolin or its derivatives, sterol, phospholipids, fatty acid, fatty acid ester, fatty alcohols etc.- They are used to impart emollient property. 

4. Healing ingredients: Example : allantoin, urea, uric acid- They help to increase the porosity of the skin.

5. Alkyl ester of poly unsaturated (C18): fatty acids, Linoleic acid and linolenic acid- They help in preventing scaling of the surface of the skin. 

6. Preservatives: like methyl paraben, propyl paraben and butyl para hydroxyl benzoate.- They prevent the growth of microorganism.

7. Perfumes: like phenyl ethyl alcohols, pine, geranium, Bourbon, lavender, light floral type etc.- They are used to impart aesthetic value to creams. 

E.g. of formula

Isopropyl myristate, mineral oil, emulsifying wax and lanolin are heated in a container. This is a mixture A. 

Glycerin, triethanolamine and water are heated in a separate container .preservative is dissolved in water before heating the mixture. this is a mixture B. 

Mixture B is added to mixture A along with continuous stirring until cream is formed. 

Perfume is added to the preparation when it reaches a temperature of 35°C. 

Finally, the preparation is passed through a triple roller mill for milling, which provides good texture. 

ALL PURPOSE CREAM

These creams are used by sport persons and also by people who do outdoor activities. Hence, they are called as sport creams.

Ideal Properties are:

• They are oily in nature but non-greasy type. 

• They provide protective film to the skin. 

• They make the rough surfaces of the skin smooth. 

• When it is applied in more quantity, it act as

(a) Nourishing agent, (b) Protective cream in order to protect the skin from sunburn., (c) Night cream. & (d) Cleansing cream.

• When it is applied in less quantity, it act as (a) Hand creams & (b) Foundation creams.

Various ingredients used:

1. Wool alcohol: It contains 28% of cholesterol which is Obtained by saponification of wool of the Sheep.- It helps in absorption of water. 

2. Antioxidants: like butylated hydroxyanisole.- It prevents oxidation. 

3. Macrocrystalline wax: It helps in easy spreading of the cream on the skin.

4. Mineral oil, paraffin: They form a protective layer on the skin. 

5. Magnesium sulphate, The ions of magnesium: It helps to increase the stability of the cream. 

6. Preservatives: like methyl paraben and propyl paraben: They inhibit the growth of microorganism. 

E.g. of formula

Wool alcohol, hard paraffin, soft paraffin, liquid paraffin and antioxidant are melted. 

Stirring is carried out until the preparation is cooled. 

Perfume is added to the preparation, when it reaches a temperature of 35°C. Hydrous 

ointment can be prepared by using the same base ingredients but with the incorporation of equal amount of water. 

THIXOTROPY, IRREVERSIBLE THIXOTROPY, ANTITHIXOTROPY

RHEOLOGY: Thixotropic behaviour of Pseudoplastic Plastic and Dialant fluid system, Irreversible thixotropy & Antithixotropy

Link for the video explaination of this topic 👇

https://youtu.be/1baGVIuWp_A

THIXOTROPY

Non-Newtonian systems such as plastic, pseudoplastic and dilatant systems at a given temperature show time dependent changes in the viscosity at varying shearing stresses. This behaviour is known as thixotropy and may be explained in the following manner:

1. Thixotropy in Plastic and Pseudoplastic Systems

In plastic and pseudoplastic systems, the viscosity gradually decreases on increases the shearing stress, at any given temperature. On removing the shearing stress, the viscosity is regained but not immediately but after some time lag. The term thixotropy is given to this phenomenon. It means "to change by touch" and may be described as a reversible isothermal transformation from gel to sol.

If a rheogram is obtained for such a system by plotting the rate of shear at various shearing stresses, a hysteresis loop is obtained. As the shearing stress is increased an up-curve is obtained. On reducing the shearing stress gradually, a down-curve is obtained. However, unlike Newtonian systems, the up-curve and the down-curve are not super-imposable. The down curve is shifted to the left side meaning that the viscosities of the down-curve are lower than that of the up-curve. This implies that the gel structure of the system is not reformed immediately but only after a lag time.

Fig: a) Thixotropy of Newtonian

b) Thixotropy of Pseudoplastic and plastic

Thixotropic systems contain asymmetric particles which set up a loose three dimensional structure. This structure confers a certain rigidity on the system and it resembles a gel. As shear is applied to the system, the structure breaks down and the material changes from a gel to a sol structure with decreasing viscosity. Upon removal of the stress, the structure begins to reform slowly and the initial structure is reformed with increasing viscosity after a lag time.

Examples of plastic systems showing thixotropy include bentonite gel and petrolatum and pseudoplastic systems showing thixotropy include dispersions of synthetic suspending agents. 

Bentonite gel is made up of a random network of hydrated elongated particles. On application of shearing stress, the elongated particles align with their long axes parallel to the direction of flow and the interparticle links are broken. The network therefore disintegrates and the apparent viscosity decreases. On removal of the shearing stress, the arrangement of dispersed particles gradually becomes less orderly under the influence of brownian motion and the gel network is reformed after a time lag.

2. Thixotropy in Dilatant Systems

In dilatant systems, an increase in the shearing stress causes an apparent increase in viscosity at a given temperature. On removal of the shearing stress, the viscosity decreases but after a lag time. This phenomenon is known as thixotropy in dilatant systems and may be described as a reversible isothermal transformation from sol to gel.

Example of dilatant systems include quicksands which exhibit thixotropic behaviour.

Fig:  Thixotropy of Dialant

Irreversible Thixotropy

The effect is similar to thixotropy. Application of shear stress causes breakdown of structure within the system but the structure does not reform on removal of the shear stress, or the time lag is so long that from a practical point of view the effect is irreversible. Examples of such systems include gels produced from high molecular weight polysaccharides which are stabilized by large number of secondary bonds. On application of high shear, the three dimensional structure of the polysaccharides is reduced to a two dimensional one and the original gel-like structure is never recovered.

Negative Thixotropy

At rest magnesia magma shows sol-like properties. On shaking, the system behaves like a gel and imparts greater suspendability. However, at equilibrium, it is readily pourable.

Antithixotropy or negative thixotropy represents an increase in consistency on the down curve. 

Fig: Antithixotropy

For example, magnesia magma exhibits an enhanced resistance to flow with increased time of shear compared to resting state. In the rheogram, the down-curve shifts to the right of the up-curve. When magnesia magma is sheared alternatively with increasing and then decreasing rates of shear, the magma thickens. As these cycles continue, the extent of increase in the thickening reduces gradually and finally reaches equilibrium state. There will be no change in the consistency curves on further cycles of shear rate. This type of behaviour is recorded.

Molecular interactions possible is : In the resting state, the system consists of a large number of individual particles and small floccules. When the product is sheared, the polymer molecular collisions are increased at a greater frequency. As a result, interparticle bonding increases. At equilibrium, large floccules are available in small numbers. However, the system exhibits sol form at equilibrium. When the product is allowed to rest, the large floccules breakup and gradually return to the original state of small floccules and individual particles.

Negative thixotropy should not be confused with the term 'dilatancy'. Dilatant systems are deflocculated and the volume of solids is high (more than 50%), whereas negative thixotropy is seen in a flocculated system containing low solid content (1 to 10%).

 QSAR (A mathematical model for Drug Design)

Link for the Video Demonstration of this topic 👇

https://youtu.be/BR2SAFdktSs

The Quantitative Structure Activity Relationship (QSAR) quantifies the relationship between physiochemical properties and biological activities. It is said to be the mathematical expression between the biological activity and the measurable physiological parameters. QSAR modelling helps prioritize a large number of chemicals in terms of their desired biological activities as an in-silico methodology and, as a result, significantly reduces the number of candidate chemicals to be tested with in vivo experiments.

The QSAR aims to identify & quantify the physiochemical properties of the drug and to see whether these properties have any effect on the biological activity.

Various physio-chemical properties being studied are:

• Hydrophobicity of the molecule

• Hydrophobicity of substituents

• Electronic properties of substituents

• Steric properties of substituents

A range of compounds is synthesized in order to vary one physicochemical property and to test if it affects the bioactivity. A graph is then drawn to plot the biological activity on the y axis versus the physicochemical feature on the x axis.

If we draw a line through a set of data points will be scattered on either side of the line. The best line will be the one closest to the data points. To measure how close the data points are , vertical lines are drawn from each point.

Few examples of QSAR software are: coMFA, coMSIA, MSI Catalyst, Serius

ADVANTAGES

• Improving the binding of drugs

• Increasing the selectivity

• Reduce side effects

• Easy synthesisable

VARIOUS PARAMETERS OF QSAR

Various parameters used for QSAR studies are:

• Lipophilic parameters.

• Electronic parameters.

• Steric parameters.

LIPOPHILIC PARAMETERS OF DRUG

Hydrophobic character of a drug is crucial to how easily it crosses the cell membrane and may also important in receptor interactions. Hydrophobicity of a drug is measured experimentally by testing the drugs relative distribution in octanol-water mixture. This relative distribution is known as partition coefficient. 

Partition Coefficient, P = [Conc. Of Drug in octanol] / [Conc.of drug in water]

Activity of drugs is often related to P. 

Biological activity log(1/c) = K1 log P + K2 

The biological activity is expressed as log (1/C), where C is the minimum concentration of the drug required to cause a defined biological response.

And the physiochemical property is expressed as log P

Eg: binding of a drug to serum albumin determined by hydrophobicity

LIPOPHILIC PROPERTIES OF SUBSTITUENTS

Partition coefficient can be calculated by knowing the contribution that various substituents, is known as substituent hydrophobicity constant(π). A measure of a substituent’s hydrophobicity relative to hydrogen. Partition coefficient is measured experimentally for a standard compound such as benzene with or without a substituent (X).The hydrophobicity constant (π x) for substituent X. The equation is 

πx= logPx - logPH

A positive π value shows that the substituent is more hydrophobic than hydrogen A negative value indicates that the substituent is less hydrophobic. The π value is characteristic for substituent.

ELECTRONIC PARAMETERS

The electronic effect of various substituents will clearly have an effect on drug ionisation and polarity. And have an effect on how easily a drug can pass through the cell membrane or how strongly it can interact with a binding site. It is generally measured by dissociation constant. 

Hammet substituent constant(σ) this is a measure of electron withdrawing or electron-donating ability of a substituents on an aromatic ring. σ for aromatic substituents is measured by comparing the dissociation constants of substituted benzoic acids with benzoic acid.

K H = Dissociation constant =   [PhCOO-]/[PhCOOH]

STERIC PARAMETERS

The bulk, size and shape of a drug will influence how easily it can approach and interact with binding site. Like a small substituent can facilitate interaction of the molecule with a receptor freely while a bulky substituents may act like a shield and hinder the ideal interaction between a drug and its binding site. However, in case of some molecule, bulky substituent shows better result. The estimation of lipophilic and electronic parameters are easy but not steric properties.

Thus Taft modified Hammer equation to measure steric parameter, like in case of Taft's constant(Es), which measures the rate of hydrolysis of aliphatic ester under acidic conditions, because here steric properties controls the hydrolysis.

Es = log Kx – log Ko

Where Kx is rate of hydrolysis of substituents

And Ko is rate of hydrolysis of parents ester.

Since Es value of F or H substituents are more that Me (CH3) because they are smaller than methyl, thus hydrolysis is faster.

While Es value of Et (ethyl) or n-Pr (propyl) are less than Me (CH3) because they are larger than methyl, thus takes time in hydrolysis.

VARIOUS STEPS INVOLVED IN QSAR

1. Selection of Lead molecule having certain biological activity

2. Calculation of various physio-chemical parameters

3. Correlation of physio-chemical properties with biological activities by QSAR method

4. Getting equation

5. Designing drug based on equation

6. Predicting the activity of the compound

7. Finally synthesizing the compound

ADVANTAGES OF QSAR

• Quantifying the relationship between drug structure and biological activity provides an understanding of the effect of structure on activity.

• QSAR allows calculation in advance, what the biological activity of the novel drug analogue maybe. Thus cutting down the number of analogs that have to be made by the chemists. Thus it helps the medical chemists in prediction of the result.

• The results can be used to help understand interactions between functional groups in the molecules of greatest activity, with those of their target.

DISADVANTAGES OF QSAR

• QSAR studies are only approximative.

• QSAR may be unuseful when many physiochemical properties are involved since it is not possible to vary one property without affecting the other and the result can cross correlate.

• False correlations may experimental error, arise due to biological data which is subject to considerable.

• If the dataset is not large enough, the data collected may not reflect the complete property. Consequently, many QSAR results cannot be used to confidently predict the most likely compounds of best activity.

FRACTIONAL DISTILLATION: Principle, Apparatus, Working, Difference between Fractional and Simple distillation, Applications, Advantages and disadvantages

 FRACTIONAL DISTILLATION

Link for Video demonstration of this topic 👇👇

https://youtu.be/22ayEgWh_pk

PRINCIPLE

It differs from simple distillation as in simple distillation, vapour pass through condenser & gets condensed which is collected into receiver while in fractional distillation, vapour pass through  fractional column where partial condensation of vapours occur & a part of condensing vapour goes to the still. This process is also known as rectification because a part of vapour is condensed & returned as liquid. 

APPARATUS

On small scale, the apparatus consists of a still in which liquid is boiled, a fractional column which is inserted between still & condenser & a condenser which is used to condense vapours. 

WORKING

The mixture of liquids with different boiling point is heated with high pressure. The mixture starts to boil & form vapour. The vapours rise to the fractional column. The vapour condenses in a condenser column. The distillate is finally received in a receiving flask. 

The fractionating column acts as a hurdle to the raising gas. It will stop non pure condensation from passing through it. The gas creates in the packing material in the fractionating column and will be again warmed up by the hot gas that will evaporate again unless it becomes pure.

 

DIFFERENCE BETWEEN SIMPLE DISTILLATION & FRACTIONAL DISTILLATION

 

USES

• Used to separate mixtures containing volatile liquids having different but close boiling points.

• Used for separation of miscible liquids, such as alcohol and water, acetone and water, chloroform and benzene.

ADVANTAGES

• Highly effective & efficient.

• Easy to use.

DISADVANTAGES

• High capital cost

• Not flexible

• Not easy to sterilize.

• Not preferred for heat sensitive products.

RHEOLOGY: Types of Viscosity, Factors affecting viscosity

 RHEOLOGY Part 3

Link for the Video Demonstration of this topic 👇

https://youtu.be/qMlkKuFO_ak

TYPES OF VISCOSITY

1. Kinematic Viscosity

The kinematic viscosity of a liquid is its absolute viscosity divided by the density at a definite temperature.

Kinematic viscosity = ŋ/ρ

The CGS unit for kinematic viscosity is the stokes (S), named after George Gabriel Stokes. It is also sometimes expressed in terms of centistokes (CS). The S.I. unit of kinematic viscosity of m²/s.

1 stoke = 100 centistokes = 1 cm²/s = 0.0001 m²/s

2. Relative viscosity

Relative viscosity (ŋr), also known as viscosity ratio is the ratio of the viscosity of a solution (ŋ) to the viscosity of the solvent used (ŋs).

3. Specific viscosity

Specific viscosity (ŋsp) may be defined as the relative increase in the viscosity of the dispersion over that of the solvent(vehicle) alone.

4. Reduced viscosity (of a polymer)

Reduced viscosity (of a polymer) or viscosity number is defined as the ratio of the specific viscosity to the concentration of the polymer (c) :

FACTORS INFLUENCING THE VISCOSITY

• Intrinsic Factors

Chemical nature, i.e., molecular size, shape and intermolecular forces, influences the viscosity. The molecular weight-the heavier the molecule of the given liquid, the greater will be the viscosity. Liquids with large and irregularly shaped molecules are generally known to be viscous compared to small and symmetric molecules. Molecular collisions between larger molecules are not elastic, i.e., involve loss of kinetic energy. Smaller particles shows better collision. As a result, intermolecular interactions are stronger in large particles and the molecules tend to stick to each other thereby increasing the viscosity of the liquid. The higher the intermolecular forces, the higher is the viscosity. Molecules with spherical shape are expected to slide past one another, and thus have low viscosity.

• Extrinsic Factors

Pressure, temperature and added substances also influence the viscosity. An increase in pressure enhances the cohesive forces of interaction, leading to an increase in the viscosity. In general, small quantities of nonelectrolytes like sucrose, glycerine and alcohol when added to the water, the solution exhibits increased viscosity. Similarly, polymers and other macromolecules enhance the viscosity of solvents such as water. On the other hand, small amounts of strong electrolytes decrease the viscosity. Alkali metals and ammonium ions are a few examples. Temperature is an important factor that needs elaborate discussion.

Temperature: As the temperature increases, the system acquires thermal energy which facilitates the breaking of the cohesive forces. The viscosity of liquid decreases. In case of gases, an increase in temperature increases the viscosity owing to the increased molecular collisions and interactions and offer resistance to flow. The relationship between viscosity and temperature may be expressed in an equation similar to Arrhenius equation as:

where  A is a constant which depends on the molecular weight and molar volume, and Ev is an 'activation energy' required to initiate the flow between the molecules, R is universal gas constant, temperature T is taken in °K.

PHARMACOKINETICS MODEL FOR DRUG DESIGN: Introduction, Application and Various models

 PHARMACOKINETICS & ITS MODEL FOR DRUG DESIGN

Link for video demonstration of this topic 👇👇

https://youtu.be/kqL3WOpY-ec (in English)

https://youtu.be/GAeHJgzJ0jk (in Hindi)

INTRODUCTION

It is a disciplinary that concerns with the study & characterization of time course of change in concentration of drug and it’s metabolites in the body fluid.

Pharmacokinetics describes what the body does to a drug i.e. The movement of drug into, through and out of the body.

The main goal of pharmacokinetics is to quantity drug’s absorption, distribution, metabolism and excretion in living organism and to use these informations to predict the effect of alteration of the drug’s dose, dosage form, route of administration, and physiological effects of drug on ADME.

IMPORTANCE

Near about 40% drug fails in it’s clinical trial due to poor ADME properties. These later stage failure contribute significant effect to the cost of new drug development. The ability to detect problems in the early stage can dramatically reduce the wastage of amount of time and resources. 

Accurate prediction of ADME properties, prior to expensive procedures can eliminate unnecessary testing of compounds that will ultimately fail. ADME prediction can also be used to  focus on lead optimization efforts to enhance the desired properties of a given compound.

Finally ADME prediction as a part of drug development process can generate compounds that are more likely to exhibit satisfactory ADME performance during clinical trial.

The increased speed of computer as well as their storage capacity has led to development of numerous software programs that now allow rapid solution of  complicated pharmacokinetic process i.e. In-silico pharmacokinetics study.

E.g. Of In-silico pharmacokinetics softwares are:

Gastroplus 

Volsurf 

Metrabase 

S-plus

Trial simulator etc.

APPLICATION OF PK SOFTWARE IN DRUG MODELING

1. Discovery

2. Candidate selection

3. Characterization of safety & pharmacokinetics of new chemical entity

4. Trail in patients to assess the efficiency

5. Dose determination

VARIOUS MATHEMATICAL MODEL

1. Zero order model: Drug dissolution from dosage form that do not disaggregate and release the drug slowly can be representing by equation:-

Where Qo = Initial conc. Of drug in the dosage form 

Qt = amount of drug in dosage form after time t

Ko = zero order release constant

Application: Used to study & design release of coated form of drug, transdermal etc.

2. First order model: This model is used to describe absorption or elimination of some drugs which release in concentration basis is expressed in form of expression:-

Where Qt = amount of drug release at time t

Qo = initial conc. Of drug

K₁ = first order rate constant

Application: Used to study & design water soluble drug in porous matrix.

3. Higuchi model: It's the first mathematical model aimed to describe drug release from matrix system proposed by Higuchi in 1961. The expression for the model is:-

Where Q = amount of drug released at time t

C = initial conc. Of drug

Cs =drug solubility in matrix media

D = diffusibility of drug from matrix surface

Application: Used to study & design low soluble drugs incorporated in semisolid/ solid polymer matrix.

4. Weibull model: It describes different dissolution process by equation:-

Where M = amount of drug dissolved as a function of time t

Mo = total amount of drug being released

T = lag time

a = scale parameter describes time dependence

b=shape of the dissolution curve progression

Application: Used for comparing release profile of matrix type drug delivery to select best formulation.

5. Hixson-crowell model: This model states that the drug release volume by dissolution changes with change in surface area or size of particle or tablet. Thus the equation is:-

Where Wo = initial conc. Of drug in dosage form

Wt = remaining amount of drug in dosage form at time t

Ks = constant representing surface-volume relationship

Application: Used to study & design dosage form like tablets where the dissolution occurs in plane that are parallel to drug's surface where the dimension diminishes but the geometric form remains constant.

6. Korsemeyer-Peppas model: This relationship helps to study drug release from polymeric system. The equation for this model is:-

Where Mt/Mꝏ = fraction of drug release at time t

K = release rate constant

n = release exponent

Application: Used to study drug release from several modified dosage form, thus helpful in designing modified dosage form.

DISTILLATION: Flash distillation

 FLASH DISTILLATION

Link for video demonstration on YouTube 👇👇

https://youtu.be/Fu2GlCA8s_w

PRINCIPLE

It is a special operation in distillation where a liquid mixture is heated & fed with a constant flow into a distillation equipment. This is a one-step operation where a liquid is partially vaporized, the vapours are in equilibrium with the residual liquid. The resulting vapor and liquid phases enter a phase separator – an equilibrium chamber – & the resulting vapours & liquid are separated & are drained separately. During the operation, the total pressure and temperature of the system, as well as the compositions of the two phases in equilibrium remain constant over time. 

APPARATUS

The apparatus consist of pump which is used to force feed into a heating chamber. As a result feed gets heated. The other end of pipe is attached to vapour separator through pressure reducing valve. There is also provision for vapor outlet at the top & liquid outlet at the bottom. At the end of the process, the vapor will be in equilibrium with liquid.

WORKING

Due to pressure drop, the hot liquid flashes. The sudden vaporisation causes cooling. The individual vapor phase molecules of high boiling fraction gets condensed & low boiling fraction stay as vapour. After some vapour & liquid phase separate & achieve equilibrium. The vapour then escaped from vapour outlet & concentrated liquid from liquid outlet.

The mixture to be separated is fed from the feed tank (1) by a pump (2) through a heat exchanger (3) at pressure P3. Here, it is heated above the boiling point it would have at P5, the pressure inside the phase separator (5). The pressure of the mixture is then decreased by flowing it through a valve (4), so that it partially evaporates and yields a vapor and liquid phase with equilibrium compositions.

USES

It is used for components with large relative volatility.

It is most commonly used in petroleum refining industries.

ADVANTAGE

It is a continuous process.

DISADVANTAGE

Not suitable when nearly pure component is required.

RHEOLOGY: Newtonian fluid and Non-newtonian fluids

RHEOLOGY Part 2

Link for Video Demonstration of the topic on my YouTube channel 👇👇👇

https://youtu.be/f7kF6z07DdI

 NEWTONIAN AND NON- NEWTONIAN FLOW

Liquids which follow Newton’s law of viscous flow are known as Newtonian liquids and those which do not follow it are known as non-Newtonian fluids.

While viscosity of Newtonian fluids remains constant, that of non-Newtonian fluids changes with change in applied shear force. While sample liquids like water, true solutions and dilute suspensions are example of Newtonian fluids, most of the pharmaceutical formulations like colloidal dispersions, emulsions, ointments or gels are examples of non-Newtonian fluids. 

NEWTONIAN FLOW

Newton was the first to study the flow properties of liquid in quantitative terms. Liquids that obey Newton’s law of flow i.e. equation 1 

F = ŋG

are called Newtonian fluids. The rheological properties of liquids are usually expressed in the form of flow diagrams or rheograms which consist of graphs showing the variation of shear rate with shear stress.

The plot for Newtonian liquid like water, simple organic liquids, true solutions and dilute suspensions and emulsions is a straight line, the slope of which is equal to the reciprocal of viscosity, a value referred to as the fluidity,

ɸ=1/ŋ ____eq.3

NON NEWTONIAN FLOW

Rheology of heterogeneous dispersion such as concentrated emulsions, suspensions and semisolids are more complex form of liquids which don not obey Newton’s equation of flow. Based of the pattern of curves, non- Newtonian fluids are:

1. Plastic fluid

2. Pseudoplastic fluid

3. Dilatant fluid 

PLASTIC FLOW

The consistency of curve for plastic fluid is given below:

The curve doesn’t pass through the origin. The substance initially behaves like an elastic body and fails to flow when less amount of stress is applied. When sufficient stress is applied with further increase in shear stress, leads to non-linear increase in the shear rate which progressively gets linearized after which it behaves like a Newtonian fluid. The linear portion when extrapolated intersects the x-axis at a point called yield value or Bingham yield value, FB or f.

The slope of  the rheogram is termed as mobility, and it’s reciprocal is known as plastic viscosity, U.

U= F – f   ___eq.4

        G

Cause of plastic flow:

Plastic  flow is considered to be the result of presence of flocculated particles in a concentrated suspension, butter, certain ointment, paste, gel or emulsion. The mechanistic explanation for the observed behaviour is as Floccules are the aggregation of particles with inter-particle contacts. This structure is maintained when the system is at rest .

Yield value represents the stress required to break the inter-particle contacts so that particles behave individually. Therefore, yield value is indicative of the forces of flocculation. More the degree of flocculation, more is the force required to bring the flow, i.e. more shear stress required. Frictional forces between moving particles also contribute to the yield value. Once the yield value exceeds, further increase in shearing stress (F-f) will bring about a proportional increase in the rate of shear.

PSEUDOPLASTIC FLOW

The consistency curve for a pseudoplastic flow begins at the origin (nearly zero at lower shear stress conditions). 

As the shear stress increases progressively, shear rate also increases, but the trend is not linear . Therefore, the viscosity of a pseudoplastic system cannot be expressed by a single value. The entire curve is the most satisfactory representation of the pseudoplastic material.

        FN = ŋ'G  ____eq.5

where 

N is a number given to the exponent 

ŋ' is the viscosity coefficient

In case of pseudoplastic fluids, N is higher than 1 and rises as the flow becomes increasingly non-Newtonian. When N = 1, equation (5) becomes equation (1), i.e., Newtonian flow. The greater the value of N above unity, the greater is the pseudoplastic behaviour of the material. Taking logarithms of both sides, equation (5) can be written as:

N log F= log ŋ' + log G ___eq.6

On rearrangement, 

log G= N log F - log ŋ' ____eq.7

In general, pseudoplastic flow is exhibited by polymer dispersions such as:

• Tragacanth in water

• Sodium alginate in water

• Methylcellulose in water

• Sodium carboxymethylcellulose in water

Cause of pseudoplastic flow:

Under normal storage conditions, the long chain molecules of the polymers are randomly arranged in the dispersion at rest. On applying a shear stress, these molecules begin to arrange their long axes or align in the direction of force applied. In addition, the solvent molecules which were earlier associated with the polymer molecules will also gets released as the polymer molecules align which reduces effectively the resistance to flow. Thus, the material becomes less viscous. Now, the material allows greater shear rate on progressive increase in the shearing stress.

DILATANT FLOW

The system exhibits enhanced resistance to flow with increasing rate of shear. When shear stress is applied, these systems increase their volume and hence are known as dilatant. Dilatant materials are also often termed as shear thickening systems because of increased apparent viscosity at higher rates of shear. When the stress is removed, the system returns to its initial state of fluidity. Dilatant flow is exhibited by:

• Highly concentrated suspensions containing solids (>50 per cent) of small, deflocculated particles.

• Suspension of starch in water.

• Inorganic pigments in water.

e.g. Kaolin 12% in water or Zinc oxide 30% in water

Cause of dilatant flow: 

Dilatant flow is exhibited by suspensions containing a high concentration of very fine particles. The particles, although in close packed arrangement are in a state of deflocculation. Flocculated suspensions on the other hand tend to show plastic flow rather than dilatancy.

When the deflocculated particles of a suspension settle, they pack into a mass of minimum volume. Only a small quantity of vehicle is needed to fill the voids between the particles but it is sufficient to allow the suspension to flow like a liquid. When the undisturbed mass is vigorously agitated, the bulk is increased as the particles force past one another. This expansion results in a larger volume between the particles and an insufficiency of vehicle to fill the voids. Thus the unlubricated particles show an increased resistance to flow and a rigid paste results.

Dilatancy does not occur in a dilute suspension where the vehicle is in great excess.

Dilatancy may prove to be troublesome during processing of dispersions and granulation of tablet masses when high speed mixers and mills are employed. If the material being processed becomes dilatant, the resulting solidification can cause overload and damage to the motor.