The History Of The Drug Delivery System

Published Date: 02 Nov 2017

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PHC 471 – Drug Delivery system

Emulsion assignment

NAME : MUHAMMAD FARHAN BIN MOHD SITH

STUDENT NO : 2011669204

CLASS: PH2104B

LECTURER : MR. AHMAD MUSTAFA

Formulation of emulsion.

Emulsion is a liquid dosage form which consist of two immiscible liquid phase, one of which

is dispersed as fine globules through the other.

To formulate an emulsion, a primary emulsion must be made. This is a very important step in preparing an emulsion. The ratio of ingredients for the primary emulsion using fixed oil is 4 : 2 : 1 (oil : water : gum). The oil parts depends on it types where it is 4 parts for fixed oil, 3 parts for mineral oil (3 : 2 : 1) and 2 parts for volatile oil (2 : 2 : 1 ) .The primary emulsion can be made through 3 methods :-

The dry gum method

In this method, the oil is added first into the mortar and pestle and triturate with the gum which are added gradually while triturating to until they are thoroughly mix. After that the 2 parts of water are added all at once and immediately triturate until it forms an emulsion which produce a "click" sounds when triturated.

The wet gum method

In this method, the water is added first into the mortar and pestle and triturate with the gum which are added gradually while triturating until they are thoroughly mix. The oil is also added gradually and slowly in portions and triturated to emulsify the oil to create the emulsion.

The Forbes bottle method

This method is used for volatile oil or oily substance with low viscosity. The gum is first added in a dry bottle which followed by the oil. The bottle is then capped and was shaken vigorously to mix them. Then the water is added in equal amount with the oil and then thoroughly shaken after each addition of water until the emulsion is formed.

Choice of emulsion type

There are several types of emulsion and it can be chosen based on the needs of the formulation and uses of the final products. The types of emulsion are:

Oil in water (O/W) emulsion.

-used when the emulsion are need to be removed easily by water such as the detergent and face.

-when oily drug are need to be delivered in oral dosage form to mask the unpleasant taste of the drug and make it more palatable

Water in oil (W/O) emulsion.

- Used when the emulsion is needed to apply to the skin as moisturizer to prevent water loss

- To increase the absorption of the drug when they are applied to the skin.

The choice of oil phase

The type of the oil will have an effect on the viscosity, rheology of the emulsion, films that are formed, and the absorption of drug into the skin. The type of oil is chosen base on the need of the formulation such as compatibility with other ingredients in the drug to provide the best stability and also the requirements of the final formulation.

The aqueous phase

The aqueous phase of the emulsion provides a good environment for the growth of bacteria. Extra precaution needs to the make when preparations contain water such as the usage of preservatives in the formulation.

Volume concentration of the dispersed phase.

The volume concentration of the dispersed phase needs to be monitored to ensure the stability of the emulsion. Too much volume of the dispersed phase may cause and inversion of the type of emulsion while too little volume might cause the emulsion to easily undergo creaming and affecting the stability of the preparation.

Particle size of dispersed phase.

The dispersed phase needs to have high surface area for better absorption and stability thus the particle size needs to be small. The reduction of the size of globules can be done through homogenization process.

Viscosity of continuous phase.

The viscosity of the continuous phase plays a major role of the product stability.

Higher viscosity of the continuous phase will slow the movement of the particles in the internal phase thus prevent them from being flocculated or coalescence thus increase the stability of the preparation

Viscosity of dispersed phase.

The viscosity of the dispersed phase has an important effect on the membrane emulsification ability. It is always more viscous than the pure continuous phase. Higher viscosity of the dispersed phase will reduce the velocity of the globules thus reducing the rate of creaming of the emulsion.

Choice of emulsifying agent.

There are various types of emulsifying agent that can be used to prepare an emulsion. The choice of emulsifying agent usually depends on what type of emulsion needs to be prepared, emulsifying ability, its route of administration, Hydrophillic-Lipophillic Balance (HLB) and also its toxicity or irritancy.

Non-ionic emulsifying is less irritant and less toxic when compared to the anionic and cationic emulsifying agents. These ionic emulsifying agents should not be used for oral preparations as they cause irritancy to the GI tract and also provides laxatives effect. Cationic surfactant are toxic to the human body even at low concentration thus should be avoided from be given orally.

Different mix of oil and water in the emulsion requires different value of HLB for the emulsifying agent. This will also affect the ability of the final products. O/W emulsion required HLB value ranging from middle to high while W/O emulsion requires HLB value ranging from low to middle. For example, Solubilizing agents requires HLB value ranging from 15-18 while anti-foaming agents requires HLB value from 1-3. Thus the HLB value of the emulsion is modified to the value where it can provide the action that is intended to be given.

Nature and concentration of emulsifying agent

Emulsifying agents can come from various sources and each type of emulsifying agents has their own properties. Some of the emulsifying agents are:

Natural emulsifying agent

Natural emulsifying agent is suitable for oral use as it is not toxic to the body. Natural products provide a good environment for bacterial growth thus contamination of the emulsifying agent may cause pyrogenic reaction upon injection. To prevent this, preservation in the emulsion is needed.

They are also incompatible with many ingredients such as phenol, heavy metal, sodium borate, tannic acid, and high concentration of alcohol and also those that have acidic properties such as sodium carboxymethylcellusose. Certain vitamins and phenolic compounds are readily oxidized by enzymes present in the natural emulsifying agent such as oxidases and peroxidases which are found in acacia. Thus the enzymes need to be destroyed first by heat before added into the emulsion.

Protein

Gelatin is a good emulsifying agent which can be obtained by partial hydrolysis of collagen. It also a good medium for bacterial growth thus requires the use of preservatives. To make a good emulsion using gelatin, high purity grade of the gelatin is required.

It acts as zwitterion and they are stable in acid and alkaline medium but have low stability at the pH where there are equal number of exposed cationic and anionic on the molecule (isoelectric point). It is negatively charged in alkaline medium while positively charged at acidic medium. To make emulsion from gelatin requires a homogenizer as normal method using mortar and pestle cannot form the emulsion.

Surfactant

Surfactant is subdivided into a few group such as anionic, cationic, and non-ionic.

Anionic surfactants are soap of long chain fatty acid and they are not used in oral preparation as they are toxic to the body. Monovalent soap provides O/W emulsion. They are more tolerable to calcium ions which contains in hard water and does not hydrolyse easily.

Cationic surfactants are amine or quarternary ammonium compound. They possess their own antibacterial activity and are stable in a wide pH range but they are incompatible with an anionic emulgent. Examples of cationic surfactants are cetylpyridinium chloride.

Finely divided solid

Finely divided solid that are wetted by both oil and water can act as emulsifying agent. They act by concentrating at the interface and produce film around dispersed droplets to prevent coalescence. They usually have mineral properties that can contain tetanus spores thus requires sterilization before usage. Examples of finely divided solid are bentonite and kaolin.

Ideal emulsifying agent

An ideal emulsifying agent should not be toxic especially if it intended to be given in oral dosage form. It should not possess any sensitizing or allergic reactions for applications to the skin. The emulsifying agent should be capable of forming a coherent film surround the globules and reduce the interfacial tension between the dispersed and continuous phase. It should also increase the viscosity the viscosity of the external phase and chemically stable to improve the stability of the emulsion. It should not decomposed by yeast, molds, bacteria and fungi. It should be cheap and has no unpleasant odour or taste and lastly and ideal emulsifying agent should be suitable over a wide range of ingredients.

Formulation by the HLB method

Preparation of emulsion using the HLB method can be used for various type and functions of the emulsion. The HLB value ranging from 1-18 where 1 indicates that it is very oil soluble and 18 indicates that it is very water soluble. Different type of emulsion need to be produced requires different value of HLB. Some of the HLB value examples are :

-mixing unlike oils (1-3)

-w/o emulsion (4-6)

-wetting powders into oil (7-9)

-self emulsifying oils (7-10)

-o/w emulsion (8-18)

-detergent (13-15)

-solubilizing agent (13-18)

A blend of emulsifying agent is usually required to produce the value of HLB required thus producing a stable emulsion.

Other formulation additives.

Additives can be added to the emulsion to improves the properties of the emulsion, stability, and acceptance of the preparation by the people. Preservatives are added when the ingredients in the emulsion are prone to bacterial contamination. Antioxidant are added to prevent product degradation during storage. Colouring and flavouring agent are added to improve the elegancy and palatability of the emulsion so that it can be easily accepted by the people and improves compliance in using the emulsion.

Evaluation of emulsion and stability testing of emulsion.

In order to evaluate the quality of the emulsion, few characteristic that affect the stability can be determined by testing the emulsion in various condition.

Degree of creaming.

there is a difficulty in measurement with accuracy (microscopic)

o/w emulsion : oil droplets is formed as the dispersed phase in an aqueous phase and the droplet rise to the interface. The time is measured when droplets rest at interface until it coalesces with the aqueous continuous phase.

w/o emulsion: aqueous droplet is formed as the dispersed phase in an oil phase and the droplet falls to the interface. The time is measured when the droplets rest at interface until it coalesces with the oil continuous phase.

Determination of globule size and its distribution in emulsion with time (particle size analyser)

Viscosity changes

Determine the specific interfacial area which consist of the surface area, mass of the surface area and volume of globules of an aging emulsion

Measurement of the lifetime of a number of drops at the oil and water interface.

Storage at adverse temperature by storing the emulsion in condition with various extreme temperature.

Centrifugation

By centrifuge the emulsion at 200-300 rpm which will accelerate the rate of creaming.