A Comprehensive Guide to Pharmaceutical Solutions: Knowledge and Precautions

I. Introduction

Pharmaceutical solutions are a common dosage form widely used in the treatment of diseases. They are homogeneous dispersions consisting of a solute (drug substance) uniformly dispersed in a solvent. Understanding the basic principles of pharmaceutical solutions helps manufacturers master the techniques of preparation, ensuring the quality and effectiveness of the drug.

II. Main components of the dispersion system

• Dispersed phase: This is the component that is evenly dispersed in the solvent. It is usually the drug substance required for treatment.

• Dispersion medium: This component surrounds and evenly disperses the dispersed phase. It is usually the solvent that dissolves the drug substance.

III. Types of Pharmaceutical Solutions by Solvent:

• Aqueous Solutions: The solvent is water, suitable for drugs that dissolve well in water.

• Alcoholic Solutions: The solvent is alcohol (ethanol), suitable for drugs that are poorly soluble in water but dissolve in alcohol.

• Oily Solutions: The solvent is oil, suitable for drugs that dissolve in oil.

IV. Advantages of Pharmaceutical Solutions:

• Rapid action: Since the drug substance is uniformly dispersed, it is easily absorbed into the body, leading to a rapid therapeutic effect.

• High bioavailability: The drug substance in the solution is easily absorbed and enters the bloodstream, increasing the bioavailability of the drug.

V. Disadvantages of Pharmaceutical Solutions:

• Susceptibility to deterioration: Pharmaceutical solutions are prone to degradation due to chemical reactions, microorganisms, or environmental factors.

• Careful storage requirements: Pharmaceutical solutions need to be stored under appropriate conditions to prevent deterioration and ensure the quality and effectiveness of the drug.

VI. Types of Chemical Bonds Affecting Solubility:

• Dipolar bond: This is the electrostatic attraction between polar molecules. Substances that dissolve in water are mainly due to dipolar bonds.

• Induced dipolar bond: This is the electrostatic attraction between polar molecules and non-polar molecules, increasing the solubility of non-polar substances in water.

• Hydrogen bond: This is the attraction between a hydrogen atom bound to a highly electronegative atom (O, N, F). Hydrogen bonding is crucial in dissolving compounds containing hydroxyl (OH) or amine (NH2) groups in water.

VII. Co-solvents with Water:

• Ethanol: Also known as ethyl alcohol, has the ability to dissolve many substances and is commonly used to prepare solvent mixtures.

• Glycerin: A polyhydric alcohol with hygroscopic properties, often used as a solvent for drugs that are poorly soluble in water.

VIII. Procedure for Preparing Pharmaceutical Solutions:

1. Weighing and measuring: Accurately weigh and measure the drug substance and solvent according to the formula.

2. Preparation: Dissolve the drug substance in the solvent and stir until the drug substance is completely dissolved.

3. Filtration: Filter the pharmaceutical solution through filter paper, cotton wool, or a membrane filter to remove any impurities, ensuring the clarity and purity of the solution.

4. Packaging: Package the pharmaceutical solution in bottles, vials, or bags as prescribed, ensuring quality and safety.

IX. Factors Affecting the Solubility of Solids in Liquids:

1. Molecular structure of the solute: The molecular structure directly affects the polarity and ability to form bonds with the solvent.

2. pH: The pH of the solvent affects the solubility of acidic or basic compounds.

3. Temperature: Temperature affects the activation energy of the dissolution reaction, increasing the solubility of most solids.

4. Presence of other substances: Other substances can increase or decrease the solubility of the solute, depending on their interactions.

5. Crystal form: Different crystal forms of the same substance have different solubilities.

X. Special Dissolution Methods:

1. Formation of a soluble carrier: Use a highly soluble carrier to dissolve with the poorly soluble drug substance, forming a soluble carrier, which is then dissolved in the solvent.

2. Using an intermediate dissolution agent: Use an intermediate agent that can form a complex with the drug substance, forming a soluble complex, which is then dissolved in the solvent.

3. Dissolution by a surface-active agent: Use a surface-active agent to form micelles that enclose and dissolve the drug substance, which is then dissolved in the solvent.

4. Using a mixed solvent: Use a mixture of two or more solvents with different properties to dissolve the drug substance.

XI. Materials Used in Filter Manufacturing:

1. Cellulose fibers: Used to filter clear solutions without any sediment, ensuring the purity of the solution.

2. Porous glass: Used to filter solutions containing sediment and able to withstand high temperatures.

3. Sponges: Used to filter solutions containing sediment, with a fast and efficient filtering ability.

4. Organic polymers, semi-synthetic cellulose derivatives: Used to filter solutions containing sediment, capable of filtering with small pore sizes, removing bacteria and molds.

XII. Filtration Methods Based on Pressure Differential:

1. Normal pressure filtration: Uses atmospheric pressure, suitable for solutions without much sediment.

2. High pressure filtration: Uses higher pressure than atmospheric pressure, suitable for solutions containing a lot of sediment, allowing faster filtration.

3. Reduced pressure filtration: Uses lower pressure than atmospheric pressure, suitable for solutions that are susceptible to degradation when exposed to high temperatures.

XIII. Advantages of Syrup Medications:

1. Suitable for children: Syrup medications are sweet, easy to swallow, and suitable for children.

2. Inhibits the growth of microorganisms: Syrup medications have a high sugar concentration, creating a hypertonic environment that limits the growth of microorganisms.

3. Pleasant taste: Syrup medications are often added with flavorings, creating a pleasant taste, making it easier for patients to take.

4. High bioavailability: The drug substance in syrup medications is easily absorbed into the body, increasing the bioavailability of the drug.

XIV. Stages in the Preparation of Syrup Medications:

1. Dissolving the drug substance: Dissolve the drug substance in the solvent according to the formula.

2. Dissolving sugar: Dissolve sugar in the drug solution and stir until the sugar is completely dissolved.

3. Adjusting the sugar concentration: Adjust the sugar concentration in the syrup medication according to regulations.

4. Filtering the syrup: Filter the syrup through filter paper, cotton wool, or a membrane filter to remove any impurities, ensuring the clarity and purity of the syrup.

XV. Equipment for Determining Sugar Concentration in Syrup:

1. Hydrometer: Used to measure the specific gravity of the syrup, based on the specific gravity to determine the sugar concentration in the syrup.

2. Baumé hydrometer: Used to measure the Baumé degree of the syrup, based on the Baumé degree to determine the sugar concentration in the syrup.

3. Can: Used to measure the volume of the syrup, based on the volume and weight of the syrup to determine the sugar concentration in the syrup.

XVI. Solubility of Solids:

• Very soluble: Less than 1 ml of solvent dissolves 1 gram of solute.

• Soluble: From 1 ml to 10 ml of solvent dissolves 1 gram of solute.

• Freely soluble: From 10 ml to 30 ml of solvent dissolves 1 gram of solute.

• Slightly soluble: From 30 ml to 100 ml of solvent dissolves 1 gram of solute.

XVII. Classification of Solvents by Polarity:

• Polar: Polar solvents are capable of dissolving polar substances. Example: water.

• Semi-polar: Semi-polar solvents are capable of dissolving both polar and non-polar substances. Example: ethanol.

• Non-polar: Non-polar solvents are capable of dissolving non-polar substances. Example: oil.

XVIII. Advantages of Ethanol as a Solvent:

• Broad solubility: Ethanol has the ability to dissolve many substances and is often used to prepare solvent mixtures.

• Antiseptic properties: Ethanol has the ability to kill bacteria, helping to preserve the pharmaceutical solution.

• Good conductor: Ethanol is a good conductor, helping to transmit electricity.

XIX. Dissolution Rate:

• Dissolution rate: The rate at which the solute dissolves in the solvent.

• D: Diffusion coefficient, indicating the rate of diffusion of solute molecules in the solvent.

• A: Surface area of contact between the solute and the solvent.

XX. Equation for Calculating the Rate of Liquid Flow through a Filter Membrane:

The rate of liquid flow through a filter membrane depends on:

• Pressure difference across the filter membrane: The greater the pressure difference, the higher the filtration rate.

• Pore size of the filter membrane: The smaller the pore size, the lower the filtration rate.

• Viscosity of the liquid: The higher the viscosity, the lower the filtration rate.

• Surface area of the filter membrane: The larger the surface area, the higher the filtration rate.

XXI. Millipore Filters:

• Millipore filters: Made from cellulose esters, with high purity, often used to filter injectable solutions, intravenous solutions.

• Nitrate: A type of cellulose ester used to manufacture Millipore filters with small pore sizes.

• Acetate: A type of cellulose ester used to manufacture Millipore filters with large pore sizes.

XXII. Chemical Changes in Pharmaceutical Solutions:

• Oxidation-reduction: Oxidation-reduction reactions occur when the drug substance is oxidized or reduced, altering the structure and properties of the drug substance.

• Hydrolysis: Hydrolysis occurs when the drug substance is broken down by water, altering the structure and properties of the drug substance.

• Racemization: Racemization occurs when the drug substance is converted from an optically active form to a non-optically active form, reducing the therapeutic effectiveness of the drug.

• Complex formation: Complex formation occurs when the drug substance binds to metal ions, forming a complex, altering the properties of the drug substance.

XXIII. Physical Changes in Pharmaceutical Solutions:

• Precipitation: The drug substance precipitates out of the solution, forming sediment, reducing the quality of the drug.

• Solidification: The pharmaceutical solution solidifies, reducing the usability of the drug.

• Color change: The color of the pharmaceutical solution changes, reducing the quality and aesthetics of the drug.

XXIV. Glycerin:

• Glycerin: A polyhydric alcohol with a specific gravity of 1.225 to 1.235, containing approximately 3% water, non-irritating, commonly used in external drug forms.

XXV. Syrup Medications according to the Vietnamese Pharmacopoeia:

• Syrup medication: A thick, liquid preparation with a sweet taste, containing sugar from 54% to 64%.

XXVI. Notes on Filtration:

• Increasing filtration efficiency: To increase filtration efficiency, it is necessary to increase the pressure difference across the filter membrane.

• Sterile filters: Sterile filters are usually Sartorius 0.22-micron filters, used to filter injectable solutions, intravenous solutions.

XXVII. Demineralized water:

• Demineralized water: The quality of demineralized water is lower than distilled water in terms of microbial indicators.

XXVIII. Popularity of Solvents:

• Popularity of solvents: Water, ethanol, glycerin are the most commonly used solvents in the preparation of pharmaceutical solutions, in decreasing order of popularity.

XXIX. Notes on Dissolving the Drug Substance:

• Rapid dissolution of the drug substance: To dissolve the drug substance quickly when preparing pharmaceutical solutions, it is best to grind the drug substance finely.

XXX. Notes on Lugol’s Solution:

• Adding KI to Lugol’s solution: Adding KI to Lugol’s solution increases the solubility of iodine.

XXXI. Preparing Digalen Solution:

• Solvent for Digalen solution: A mixture of water, glycerin, and ethanol is used to prepare Digalen solution.

XXXII. Antioxidant for Oil Solutions:

• Antioxidant for oil solutions: Vitamin E is used as an antioxidant for oil solutions.

XXXIII. Critical Stage in the Preparation of Simple Syrup:

• Critical stage in the preparation of simple syrup: The stage of dissolving sugar is the most important stage in the preparation of simple syrup.

XXXIV. Preparing Bromoform Solution:

• Solvent for bromoform solution: A mixture of ethanol and glycerin is used to prepare bromoform solution.

XXXV. Demineralized water cannot replace distilled water:

• Demineralized water cannot replace distilled water: Demineralized water cannot replace distilled water in the preparation of injectable solutions.

XXXVI. Solvent not used to prepare oral solutions:

• Solvent not used to prepare oral solutions: Methanol cannot be used to prepare oral solutions.

XXXVII. Preparing Aromatic Water:

• Preparing aromatic water with a high oil content: Use the surface-active agent Tween 20 as an intermediate dissolution agent to prepare aromatic water with a high oil content.

XXXVIII. Specific gravity and Baumé degree of simple syrup:

• Simple syrup with 64% sugar content: Corresponds to a specific gravity of 1.32 at 20 degrees Celsius.

• Syrup with a specific gravity of 1.32: Corresponds to a Baumé degree of 35 degrees.

XXXIX. Substances with reduced solubility as temperature increases:

• Substances with reduced solubility as temperature increases: Sodium sulfate is a substance that has reduced solubility as temperature increases.

XL. Oil that dissolves most in absolute ethanol:

• Oil that dissolves most in absolute ethanol: Castor oil is the oil that dissolves most in absolute ethanol.

XLI. Solutions are dispersion systems:

• Solutions are dispersion systems: Solutions are dispersion systems with two components: the solute and the solvent.

XLII. Homogeneous dispersion system:

• Solutions are homogeneous dispersion systems: In solutions, the dispersed phase and dispersion medium form a homogeneous mixture.

XLIII. Solubility:

• Solubility: The minimum number of ml of solvent required to dissolve 1 gram of solute at 20 degrees Celsius.

XLIV. Compounds with solubility in water:

• Compounds with solubility in water from high to low: Resocrinol > phenol > chloroform > benzene.

• Compounds with solubility in water from high to low: Quinine dichloride > quinine chloride > quinine.

XLV. Methods to increase the solubility of poorly soluble substances:

• Methods to increase the solubility of poorly soluble substances: Use a surface-active agent as an intermediate dissolution agent.

XLVI. Using surface-active agents as intermediate dissolution agents:

• Using surface-active agents as intermediate dissolution agents: Use a surface-active agent at a concentration greater than the critical micelle concentration.

XLVII. Equipment for filtering simple syrup:

• Equipment for filtering simple syrup: Fabric filter bags are suitable for filtering simple syrup.

XLVIII. Amount of sugar required for simple syrup:

• Amount of sugar required for 100 ml of water in simple syrup (dissolved cold): 180g.

• Amount of sugar required for 100 ml of water in simple syrup (dissolved hot): 165g.

XLIX. Role of sodium benzoate in 7% caffeine injection:

• Role of sodium benzoate in 7% caffeine injection: Acts as an agent to increase the solubility of caffeine by the intermediate dissolution mechanism.

L. Role of urethane in quinine injection:

• Role of urethane in quinine injection: Urethane is a preservative that helps to preserve the quinine injection solution.

LI. Role of Tween in star anise oil:

• Role of Tween in star anise oil: Increases the solubility of star anise oil by the mechanism of a surface-active agent acting as an intermediate dissolution agent.

LII. Decomposition of epinephrine:

• Decomposition of epinephrine: Epinephrine decomposes rapidly at neutral or alkaline pH due to oxidation.

LIII. Decomposition of vitamin C:

• Decomposition of vitamin C: Vitamin C decomposes rapidly at any pH due to oxidation.

LIV. Limiting oxidation in drug solutions:

• Limiting oxidation in drug solutions:

• Add antioxidants.

• Adjust the pH to the stable pH of the drug substance.

• Store in a cool, dark place.

• Use substances that can form complexes to deactivate metal ions.

LV. Limiting hydrolysis in drug solutions:

• Limiting hydrolysis in drug solutions: Adjust the pH appropriately.

LVI. Antioxidant for vitamin C solutions:

• Antioxidant for vitamin C solutions: Sodium bisulfite.

LVII. Preparing the formula for Digalen solution:

• Preparing the formula for Digalen solution: Dissolve Digalen in alcohol, then add glycerin and water.

LVIII. Factors affecting solubility:

• Factors affecting solubility:

• Dielectric constant.

• pH of the solution.

• pKa of the solute.

• Solubility parameters.

LIX. Hydroxyl group:

• Hydroxyl group: Solubility in water increases as the number of hydroxyl groups increases.

LX. Substance with the greatest solubility in water:

• Substance with the greatest solubility in water: Tert-butanol.

LXI. Differences in polymorphism:

• Differences in polymorphism: Different polymorphic crystal forms of the same drug substance lead to differences in melting point and solubility.

LXII. Shrinkage of ethanol and water mixtures:

• Shrinkage of ethanol and water mixtures: Shrinkage occurs by about 3% when ethanol is mixed with distilled water, mainly due to hydrogen bonding.

LXIII. Most hygroscopic liquid:

• Most hygroscopic liquid: Glycerin.

LXIV. Factors affecting filtration rate:

• Most important factor affecting filtration rate: Pore diameter.

LXV. Methyl paraben preservative:

• Methyl paraben preservative: An ester of p-hydroxybenzoic acid.

LXVI. Structure of a surface-active agent:

• Structure of a surface-active agent: Contains both water-soluble and oil-soluble groups in the same molecule.

Note:

• The above article is a basic knowledge about pharmaceutical solutions. Readers need to refer to more specialized materials to master the knowledge and techniques of drug preparation.

• The preparation of drugs requires high accuracy and care, so strictly adhere to the procedures and instructions.

• Drug manufacturers must have professional knowledge, skills, and experience to ensure the quality and safety of the drug.