**SUPPLEMENTARY ARTICLE ON PHARMACEUTICAL FORMULATION**

This article provides basic knowledge about pharmaceutical formulation, including factors affecting the solubility, stability, preservation, and filtration of drug substances.

1. Solubility:

• Factors affecting solubility:

• Nature of the solute and solvent:

• Similarity in polarity: Substances with similar polarity will dissolve easily in each other. For example, water is a polar solvent, dissolving polar substances like sugar and salt well. Ethanol is a less polar solvent, dissolving less polar substances like oil and fat well.

• Presence of hydrogen bonds: Substances capable of forming hydrogen bonds with the solvent will dissolve more readily.

• Size and shape of the molecule: Smaller molecules with simple shapes will dissolve more easily.

• Temperature:

• Solids: The solubility of solids generally increases with increasing temperature.

• Gases: The solubility of gases generally decreases with increasing temperature.

• Pressure:

• Gases: The solubility of gases generally increases with increasing pressure.

• pH:

• Weak electrolytes: The solubility of weak electrolytes depends on the pH of the solution.

• Amphoteric substances: Amphoteric substances (proteins, amino acids) precipitate at their isoelectric point.

• Presence of other substances:

• Electrolytes: Can increase or decrease the solubility of the solute.

• Complexing agents: Form complexes with the solute, increasing solubility. For example, PVP forms complexes with sulfonamide antibiotics.

• Related terms:

• Freely soluble: Soluble in a small amount of solvent (not more than 10 ml).

• Sparingly soluble: Soluble in a large amount of solvent (from 100 ml to 1000 ml).

• Very sparingly soluble: Soluble in a very large amount of solvent (over 10000 ml).

• Practically insoluble: Not soluble in the solvent.

• Note:

• The solubility of the solute is an important factor in pharmaceutical formulation.

• It is necessary to choose an appropriate solvent to ensure the solubility of the drug substance.

• Factors affecting solubility should be considered to prevent precipitation during formulation.

2. Stability:

• Factors affecting stability:

• Chemical degradation:

• Hydrolysis: Reaction with water.

• Oxidation: Reaction with oxygen.

• Racemization: Change in chiral structure.

• Physical degradation:

• Precipitation: Separation from the solution.

• Structural change: Change in the shape of the molecule.

• Environmental factors:

• Temperature: High temperatures increase the rate of degradation.

• Light: Light can cause oxidation or degradation.

• Humidity: High humidity can cause hydrolysis.

• pH: The pH of the solution can affect the stability of the drug substance.

• Methods to enhance stability:

• pH adjustment: Use buffers to maintain a stable pH.

• Solvent change: Choose a solvent capable of dissolving and protecting the drug substance.

• Chemical structure modification: Modify the chemical structure of the drug substance to increase stability.

• Use of preservatives: Add preservatives to prevent the growth of microorganisms.

• Storage at low temperatures: Store at low temperatures to reduce the rate of degradation reactions.

• Storage in dark conditions: Store in dark conditions to avoid exposure to light.

• Note:

• It is important to thoroughly study the stability characteristics of the drug substance before formulation.

• It is necessary to consider factors affecting stability to choose an appropriate preservation method.

• Use appropriate methods to enhance the stability of the drug substance.

3. Filtration:

• Purpose:

• Remove solid impurities.

• Remove microorganisms.

• Enhance the clarity of the solution.

• Filtration methods:

• Paper filtration:

• Thick and loose paper filter: Used to filter viscous solutions, syrups, oils (pore size about 10 microns).

• Medium paper filter: Used to filter drug solutions (pore size about 3-7 microns).

• Membrane filtration:

• Semi-synthetic membrane filter: Cellulose esters, cellulose acetophtalate, soluble in acetone, alcohol, water.

• Sterile membrane filter: Has a pore size of 0.22 microns, removing microorganisms.

• Fabric filtration: Used for solutions with high viscosity.

• Cotton filtration: Used for external solutions.

• Factors affecting filtration efficiency:

• Pore size of the filter material: It is necessary to choose a filter material suitable for the size of the impurities to be removed.

• Filtration pressure: High filtration pressure will increase the filtration rate but can damage the filter material.

• Viscosity of the solution: Solutions with high viscosity will be more difficult to filter.

• Properties of the impurities: Different impurities will affect filtration efficiency.

• Note:

• It is necessary to choose an appropriate filtration method for the type of solution and the purpose of filtration.

• It is necessary to check the quality of the solution after filtration to ensure the efficiency of the filtration process.

4. Other factors:

• Solvent:

• Polar solvent: Dissolves polar substances and ionized solutes well.

• Non-polar solvent: Dissolves non-polar substances well.

• Solvent mixtures: Use solvent mixtures to enhance the solubility of the drug substance.

• Preservatives:

• To prevent microbial contamination by oral route: Nipagin, nipasol, benzoic acid, ethanol.

• To prevent microbial contamination by injection route: Phenol, phenol derivatives, organic mercury derivatives.

• Antioxidants:

• For oil media: BHT, BHA.

• For aqueous media: Sodium sulfite, sodium bisulfite, ascorbic acid.

• Complexing agents:

• Form complexes with the drug substance to enhance solubility or stability. For example, PVP forms complexes with sulfonamide antibiotics.

• Electrolytes:

• Can increase or decrease the solubility of the solute.

• Can cause precipitation when added to a solution containing a solute.

• Colloids:

• Can cause turbidity in the solution.

• Can flocculate due to electrolytes, pH, aging phenomenon.

General notes:

• Knowledge about pharmaceutical formulation is complex and requires thorough research.

• It is necessary to consult with pharmaceutical formulation experts to ensure the quality and safety of the product.

• It is necessary to comply with the regulations on pharmaceutical formulation issued by the health regulatory agency.

This article only provides basic knowledge about pharmaceutical formulation. For further study, you should refer to specialized literature on pharmaceutical formulation.