Pharmaceutical Preparations Practice 1: Solutions, Syrups, Potions, Elixirs, Eye Drops, Tinctures, Spirits, Extracts, Emulsions and Suspensions

1. Pharmaceutical Solutions

• Definition: A pharmaceutical solution is a liquid preparation that is made by dissolving one or more medicinal substances in a solvent or mixture of solvents.

• Routes of administration:

• Oral (swallowing, injection)

• Topical (applying, washing, eye drops, ear drops, nose drops)

• Components of a Pharmaceutical Solution:

• Solutes:

• Medicinal substances:

• Choose the desired dosage form (salt, crystal, powder…)

• Choose the correct solvent (polar, semi-polar, non-polar)

• Auxiliary substances:

• Stabilizers: Antioxidants (sodium metabisulfite, vitamin C…), anti-hydrolytics (citric acid, tartaric acid…)

• Solubility enhancers: Increase the solubility of the medicinal substance (PEG, glycerin, ethanol…)

• Preservatives: Prevent the growth of microorganisms (nipagin, nipasol, methyl paraben…)

• Buffering agents, pH adjusters: Maintain stable pH (citric acid, tartaric acid, boric acid…)

• Isotonic agents: Adjust the osmotic pressure of the solution (NaCl, KCl, glucose, mannitol…)

• Solvent:

• No pharmacological effect, non-toxic, non-incompatible with medicinal substances and packaging.

• Strong polar solvents: Water, ethanol, glycerin

• Weakly polar or semi-polar solvents: Acetone, chloroform…

• Non-polar solvents: Ether, paraffin oil, vegetable oils…

• Note:

• It is necessary to choose a solvent that is compatible with the medicinal substance to ensure the solubility and stability of the drug.

• Check the clarity of the solution, if there is sediment, filter it out.

• Store the solution properly to avoid contamination, oxidation, and decomposition.

• Special dissolution methods:

• Formation of easily soluble derivatives:

• Principle: Use a substance that forms an easily soluble derivative with the medicinal substance. The derivative formed retains the biological activity of the original medicinal substance.

• Example: Dissolving I2 in a KI solution to form KI3 which is easily soluble in water.

• Using water-soluble intermediates:

• Principle: Use substances with hydrophilic groups such as -COOH, -OH, -NH2, -SO3H…, the rest are lipophilic hydrocarbons.

• Example: Use propylene glycol as an intermediate to dissolve paracetamol.

• Using a mixture of solvents:

• Principle: A mixture of solvents changes the solubility of the medicinal substance by changing the polarity, making the semi-polar solvent a mixture of strong polar solvents…

• Example: Use a mixture of ethanol and water to dissolve medicinal substances with different solubilities.

• Using surfactants:

• Principle: The concentration of surfactant > critical micelle concentration to form micelle structures that attract insoluble substances dispersed in the solvent → Pseudo-solution.

• Example: Use polysorbate 80 to dissolve substances that are insoluble in water.

• Dissolution sequence:

• According to solubility: Less soluble substances are dissolved first, more soluble substances are dissolved later.

• Mixture of solvents: Prepare the mixture of solvents first

• Solubility enhancers are dissolved before the medicinal substance

• If using an intermediate solvent, dissolve the medicinal substance in the intermediate solvent before combining it into the solution

• Antioxidants, buffers, preservatives are dissolved before dissolving the medicinal substance

• Tinctures, liquid extracts (prepared potions) are combined with the solvent with high viscosity first

• Soft extracts, thick extracts are dissolved in syrups, hot glycerin

• Fragrant, volatile substances are dissolved last, dissolved in a sealed container

• Examples:

• Lugol’s Solution:

• Use: Treating goiter and detoxifying alkaloids

• Dosage: Take orally by drops and dilute in a glass of water. Dosage according to the doctor’s instructions.

• Why is KI used in Lugol’s Solution?

• KI is a solubility enhancer that helps I2 (insoluble in water) to form KI3 (soluble)

• Why should potassium iodide be dissolved in 1-2 ml of water?

• Because I2 + KI => KI3 (soluble in water). KI is only dissolved in 1-2ml of water to create a concentrated KI solution and easily dissolve I2. Adding too much water will hinder the ability of I2 to react with KI

• Dalibour’s Solution:

• Use: Used to wash and apply in cases of eczema and fungi.

• Role of the substances in the Dalibour formula:

• Copper sulfate (CuSO4), Zinc sulfate (ZnSO4): Antibacterial medicinal substances

• Camphor spirit: Antiseptic, reduces itching

• 0.1% picric acid solution: Antiseptic, promotes rapid wound healing

• Why should copper sulfate and zinc sulfate be dissolved in the maximum possible amount of water before adding camphor spirit?

• Because camphor spirit is volatile and difficult to dissolve, CuSO4 and ZnSO4 are dissolved in 95ml of water first to avoid the volatilization of camphor spirit and to achieve the maximum liquid level to dissolve camphor spirit.

• Why use camphor spirit instead of camphor?

• Because camphor is insoluble in water, only soluble in alcohol, so camphor spirit is used so that camphor dissolves in the solution.

• Why should camphor spirit be added slowly?

• Camphor spirit is difficult to dissolve in water, so if added quickly, it will precipitate, so it should be added drop by drop and stirred vigorously.

2. Pharmaceutical Syrups

• Definition: A pharmaceutical syrup is a sweet, viscous liquid preparation containing a high percentage of sugar (56-64%).

• Route of administration: Taken orally.

• Components:

• Medicinal substance

• Simple syrup/saccharose

• Solubility enhancers, taste masking agents and stabilizers: glycerin, propylene glycol, ethanol

• Viscosity enhancers: NaCMC, PEG 1500…

• Buffering agents, pH adjusters: citric acid, tartaric acid, HCl, NaOH…

• Antioxidants: Na2EDTA, sodium metabisulfite…

• Anti-fungal preservatives: nipagin, nipasol

• Colorants, flavorings

• Advantages:

• Hypertonic solution -> inhibits bacteria, fungi

• Masks unpleasant tastes of drugs

• Suitable for children

• High taste masking

• Nutritional benefits

• Disadvantages:

• Easily contaminated with bacteria, fungi if not prepared and stored properly

• Bulky, inaccurate dosing

• Active ingredients are easily degraded

• Easy crystallization of sugar

• Not suitable for patients on a sugar-free diet

• Syrup preparation techniques:

• Dissolving medicinal substances, medicinal solutions in simple syrup:

• Prepare simple syrup

• Prepare the medicinal solution

• Dissolve/combine the medicinal solution into simple syrup

• Complete the preparation

• Dissolving sugar into a medicinal solution:

• Prepare the medicinal solution

• Dissolve sugar into the medicinal solution

• Check and adjust the sugar concentration

• Filter, clarify, complete the preparation

• Advantages and disadvantages of preparing simple syrup hot and cold:

• Hot:

• Advantages: Dissolves and filters quickly, reduces risk of contamination

• Disadvantages: Caramelization, colored; sugar is easily hydrolyzed

• Cold:

• Advantages: Avoids caramelization, colorless product, sugar is not hydrolyzed

• Disadvantages: Preparation takes a long time, easy contamination during preparation

• Explain the method of filtering and clarifying pharmaceutical syrups?

• Filtering and clarifying:

• Filter paper with large pores/cloth bag

• Auxiliary filtration measures

• Use filter paper 1g # 1000g syrup → does not introduce foreign impurities into the syrup.

• Use egg whites 1 egg white #10 liters of syrup (stir well). Disadvantage: introduces some small-molecule proteins that are soluble into the syrup, which may cause incompatibility with DC.

• Hot filtration

• Decolorization with activated charcoal 3-5% (not used for pharmaceutical syrups)

• Examples:

• Iodotanic Syrup:

• Indications: Used to treat general debility, tuberculosis lymphadenitis.

• Storage: Do not store in a cold place, avoid sunlight.

• Why should sugar be added in two steps into the solution?

• Because if 30g is used all at once, the solution will be too thick and viscous, the high viscosity will prevent iodine and tannin from reacting with each other.

• Only 5g of sugar is added to the conical flask at the beginning to create just enough viscosity to prevent iodine from subliming.

• What should be noted to make the reaction happen quickly?

• Shake to increase the contact area between tannin and iodine.

• Avoid making the solution too thick and viscous as this prevents iodine and tannin from reacting with each other.

• How to know if iodine has reacted completely?

• Use starch-coated paper:

• If the paper turns brown -> iodine is exhausted

• If the paper turns purple -> iodine remains

3. Potions

• Definition: A potion is a sweet, liquid preparation containing one or more medicinal substances, sugar concentration: 10-15%.

• Route of administration: Usually prepared according to the prescription and taken with a tablespoon.

• Components:

• Various medicinal substances: tinctures, extracts, chemicals

• Solvent: distilled water, aromatic water, infusion, decoction of medicinal herbs, low-degree alcohol

• Sweeteners: simple syrup, pharmaceutical syrup or a mixture of syrups

• Precautions during potion preparation:

• Potions are usually prepared directly in the bottle that has been marked with the volume.

• Potions containing tinctures, liquid extracts -> mix the tinctures, liquid extracts with the amount of syrup in the prescription before adding other medicinal substances and excipients. If the amount of tincture is less than 2g, it can be taken by drops, using a calibrated dropper. If the amount of tincture is more than 2g, it must be weighed.

• Soft extracts and thick extracts are usually dissolved in syrups or hot glycerin.

• Medicinal substances that are soluble in the solvent and excipient are usually dissolved first and filtered into the bottle.

• For potions containing medicinal herbs, the water must be boiled to decoct or infuse the medicinal herbs. The ratio of medicinal herbs usually used to prepare decoctions or infusions is 2% (medicinal herbs are leaves and flowers) and 4% (medicinal herbs are wood, stem, roots).

• Note:

• Due to the low amount of sugar -> potions are a favorable environment for the growth of bacteria, fungi.

• Only prepare when used or for use in 1 – 2 days (60- 125 ml), fill the bottle.

• Store in a tightly sealed bottle, in a cool place.

4. Elixirs

• Definition: Elixir is a sweet, liquid preparation containing 1 or more medicinal substances, with a high proportion of ethanol, polyalcohols, propylene glycol.

• Route of administration: Dosage is measured in teaspoons.

• Advantages:

• Easy to use, pleasant taste.

• Active substances are easily absorbed.

• Disadvantages:

• Contains alcohol, not suitable for children, pregnant women and breastfeeding mothers.

• Easy to evaporate, needs to be stored in a sealed container.

• Components:

• Medicinal substance

• Solvent: ethanol, glycerin, propylene glycol

• Sweeteners: sugar, simple syrup, saccharin

• Flavoring agents: essential oils, flavorings

• Examples:

• Paracetamol Elixir:

• Use: Pain relief, fever reduction.

• Dosage: Take as directed by your doctor.

• Dosage:

• Children under 2 years old: Not for use

• Children 2-6 years old: 125mg/dose, maximum 4 doses/day

• Children 6-12 years old: 250mg/dose, maximum 4 doses/day

• Children over 12 years old and adults: 500mg/dose, maximum 4 doses/day

5. Eye Drops

• Definition: Eye drops are a sterile liquid preparation, a solution or suspension, containing one or more medicinal substances and auxiliary substances (isotonic, pH adjuster, antiseptic…)

• Route of administration: Instilled into the conjunctival sac for diagnosis or treatment of eye diseases.

• Components:

• Medicinal substance

• Excipients:

• Antiseptics: benzalkonium chloride, PMN, PMA, Thimerosal, parabens…

• pH adjusters: boric-borate, citric-citrate, phosphate…

• Isotonic agents: NaCl, KCl, mannitol, glucose…

• Antioxidants: sodium sulfite, sodium bisulfite, sodium metabisulfite, Disodium edetate

• Viscosity enhancers: polymers to prolong drug retention on the cornea.

• Surfactants

• Packaging:

• Dropper bottle, sterile eye drop bottle, individually packaged.

• Note:

• It is necessary to ensure absolute sterility for eye drops.

• Store eye drops properly to avoid contamination and decomposition.

• Do not share eye drops with others.

• Do not use eye drops if you have any unusual signs in your eyes.

• Consult a doctor before using eye drops.

• Examples:

• Eye drops for the treatment of conjunctivitis:

• Components:

• Medicinal substance: Ofloxacin 0.3%

• Excipients: benzalkonium chloride 0.01%, sodium chloride, sodium borate, purified water qs 10 ml.

• Use: Treating bacterial conjunctivitis.

• Dosage: Instill 1-2 drops into the inflamed eye, 4 times a day.

6. Tinctures

• Definition: A tincture is a liquid preparation made by extracting active substances from medicinal herbs or dissolving extracts, chemicals in ethanol.

• Classification:

• By composition: Single tincture, compound tincture

• By preparation method: Infusion, percolation, dissolution.

• Components:

• Medicinal herbs: Meet the standards for the content of active substances, moisture, impurity ratio. Size is finely divided to the appropriate fineness.

• Solvent: Ethanol (USP III) solubility changes with concentration

• Ethanol 30o – 60o active substances are easily soluble in water

• Ethanol 70o alkaloids, glycosides

• Ethanol 80-90o essential oils, aromatic resins

• Ethanol 90-95o medicinal herbs with active substances that are easily hydrolyzed.

• Note:

• Store tinctures in sealed bottles, away from light, and high temperatures.

• Do not use expired tinctures.

7. Spirits

• Definition: Spirit is a liquid preparation made by dissolving extracts of medicinal herbs, already processed, with wine or ethanol (appropriate concentration), adding flavoring and sweetening agents.

• Route of administration: Used for oral administration.

• Components:

• Medicinal herbs

• Solvent: Wine or ethanol

• Auxiliary substances: Flavoring, sweetening agents

• Spirit preparation techniques:

• Preparation of raw materials and solvents

• Extraction methods for preparing extracts

• Combining extracts

• Adding flavoring, sweetening agents and colorants

• Completing the preparation and packaging.

8. Extracts

• Definition: Extracts are liquid, thick or dry preparations made by concentrating or drying herbal extracts.

• Route of administration: Rarely used directly, used to prepare: syrups, potions, tablets, ointments, suppositories, eggs, tablets.

• Components:

• Medicinal herbs

• Solvent: water, ethanol, diluted ethanol, ethanol-glycerin-water, ethanol-water

• Extract preparation techniques:

• Preparation of extracts

• Removing impurities from extracts

• Concentration or drying

• Completing the preparation

• Examples:

• Orange peel extract:

• Use: Cough suppressant, expectorant.

• Dosage: Used to prepare syrups, tablets.

• Why use orange peel tincture instead of using orange peel directly?

• Because orange peel contains essential oils with a fragrant aroma (which are added to the extract to mask unpleasant smells), but essential oils in orange peel evaporate at room temperature, are not soluble in DMPC and easily soluble in DMKPC. Therefore, orange peel tincture is prepared to stabilize the concentration of orange peel and easily dissolve in other medicinal substances.

9. Pharmaceutical Emulsions

• Definition: A pharmaceutical emulsion is a liquid or soft preparation made by using suitable emulsifiers to mix two immiscible liquids, conventionally known as oil and water.

• Route of administration: Used for oral, injection, topical administration.

• Components:

• Water phase: Polar liquid

• Oil phase: Non-polar or very slightly polar liquid

• Emulsifier

• Emulsifier:

• A special intermediate that helps the emulsion to form and have a certain stability

• When the dispersed phase concentration ≤ 2%, emulsifiers may not be needed

• When the dispersed phase concentration > 2%, emulsifiers must be used (stable emulsion)

• Classification of emulsifiers:

• Surfactant emulsifiers: Increase the dispersion capacity of the dispersed phase in the dispersion medium.

• Hydrophilic colloid emulsifiers: Create a protective film around small droplets, preventing them from merging.

• Solid, very small particle emulsifiers: Create a barrier between small droplets, preventing them from merging.

• Role of emulsifiers:

• Determine the type of emulsion and help to stabilize them by preventing the aggregation of small droplets into large droplets, leading to separation.

• Emulsifiers that are soluble in water will create an O/W emulsion; emulsifiers that are soluble in oil, fats, waxes will create a W/O emulsion.

• Examples:

• Bromoform Emulsion:

• Use: Anti-cough.

• Dosage: Take as directed by your doctor.

• Why should the mixture be heated before emulsification?

• To reduce the viscosity of the oil and increase the emulsifying ability.

• Why should gum arabic be used?

• Gum arabic is an emulsifier, reduces surface tension, helping the dispersed phase to disperse evenly in the dispersion medium.

10. Pharmaceutical Suspensions

• Definition: A suspension is a liquid preparation for oral, injection or topical use, containing at least one insoluble solid substance that is dispersed evenly in the form of fine or ultra-fine particles in a carrier such as water or oil.

• Quality requirements:

• Suspensions are bottled in bottles with a volume greater than the volume of the suspension needed to be stored. “Shake well before use”. When left undisturbed, the dispersed solid substance may separate into a separate layer but must return to a uniform state of dispersion in the carrier when the bottle is shaken gently for 1-2 minutes and maintain that state of uniform dispersion for a few minutes.

• Components:

• Medicinal substance (hydrophilic or lipophilic)

• Dispersion medium: Liquid and excipients dissolved in it.

• Wetting agent (if necessary)

• Surfactants

• Hydrophilic colloids of large molecules

• Hydrophilic solid particles in small sizes

• Suspension preparation techniques:

• Dispersion method:

• Step 1: Dry grinding

• Step 2: Wet grinding

• Step 3: Dispersing the finely ground paste of the solid substance into the carrier

• Precipitation method

• Precipitation due to changes in solvent

• Precipitation due to the formation of a precipitate by PUHH

• Examples:

• Terpin Hydrate Suspension:

• Use: Anti-cough, expectorant.

• Dosage: Take as directed by your doctor.

• Why prepare terpin hydrate suspension?

• Terpin hydrate is poorly soluble in water, so it needs to be prepared in suspension form to enhance absorption.

• Dosage?

• The dosage of terpin hydrate is 0.25 – 0.5 g/dose, 3-4 doses/day.

• Can other wetting agents be used?

• Other wetting agents can be used such as: polysorbate 80, sodium lauryl sulfate…

General notes:

• Rewriting and adding comprehensive, detailed information to each article.

• It is necessary to pay attention to the requirements for sterility, storage, and safety during drug preparation.

• Add notes to each article, for example:

• Emulsifiers need to be chosen according to the type of emulsion, the nature of the dispersed phase and the dispersion medium.

• It is necessary to check the dispersion of the suspension by letting the suspension stand for a few minutes, then shake gently and observe whether the suspension returns to a uniform state of dispersion.

Sections to be added:

• Add more examples of solutions, syrups, potions, elixirs, eye drops, tinctures, spirits, extracts, emulsions, and suspensions.

• Add more information about other preparation methods, for example: Infusion method, decoction method, melting method…

• Add more information about other excipients, for example: Viscosity enhancers, colorants, flavoring agents…

Note:

• The information provided in the article is for reference only and does not replace advice from a doctor or pharmacist.

• Before using any medicine, you should consult with your doctor or pharmacist.