Dilution of Solid/Semi-Solid Formulations Study Notes

Tutorial: Dilution of Solid/Semi-Solid Formulations

1. Introduction

• Principles of dilution outlined in the tutorial for liquid formulations apply to solid and semi-solid formulations as well.

• In preparing solid (powder) and semi-solid (cream, ointment, gel) formulations with low concentrations of active ingredients, accuracy in weighing is crucial.

• Consideration should be given to the sensitivity of the balance and the Minimum Weighable Mass (MWM) when measuring ingredients.

• Terms used:

  • Attenuation: A dilution process achieved physically, typically by mixing in a mortar or by trituration on an ointment slab.

  • Trituration: A specific method for preparing a semi-solid formulation by mixing a concentrated drug into a base.

• Stock formulation: Refers to powder or semi-solid formulations containing higher concentrations of active ingredients used for subsequent dilutions.

2. Objectives

• Understanding the dilution of powder and semi-solid formulations.

• Recognizing constraints of available equipment in creating accurate formulations.

• End outcomes of the tutorial include:

  • a) Knowledge when to make a dilution.

  • b) Comprehension of ratio strength and dilution factors.

  • c) Ability to determine amounts of stock formulations corresponding to required active ingredient doses.

  • d) Mastery in creating dilutions of stock formulations to desired strengths.

  • e) Skills to calculate active ingredient amounts in diluted formulations.

  • f) Understanding how to apply the alligation formula for dilution.

3. Decision to Make a Dilution

• A decision to dilute is influenced by balance sensitivity and the amount that needs to be weighed with precision, especially crucial for drugs with narrow therapeutic indices.

• Aim: Measure quantities with the least error.

3.1 Example: Dilution of Atropine Sulphate

• 200 mg of Atropine Sulphate is weighed and diluted to 10 g total (utilizing 9.8 g of Lactose).

• Initial preparation: 1 g of this mix is weighed and further diluted to 8 g with Lactose (7 g of Lactose added).

• Final weighing involves obtaining 200 mg of the second mix, corresponding to 0.5 mg of Atropine Sulphate.

4. Practice Questions and Worked Examples

4.1 Worked Example 1: Overview of Steps to Dilution

• Minimum Weighable Mass (MWM) calculated: For a 5% error, MWM = 20 x balance sensitivity.

• Calculate total drug needed:

  • Amount of Atropine Sulphate required: 0.5 mg/capsule x 10 capsules = 5 mg

  • Lactose needed: 199.5 mg x 10 = 1995 mg

  • First dilution: Weigh 200 mg of Atropine Sulphate, dilute to 10 g with Lactose (this results in 200 mg drug/10,000 mg mix; we want to achieve 5 mg drug in x mg mix).

  • Solve for x: x = rac{5mg}{( rac{200mg}{10000mg})} = 250mg.

• Determine additional Lactose: 1995 mg - (250 mg - 5 mg) = 1750 mg additional Lactose.

• Second dilution: Take 250 mg of the powder mix and triturate with 1750 mg Lactose.

• Weigh: 200 mg portions of the final mix into gelatin capsules.

4.2 Worked Example 2: Error Assessment in Weighings

• Accumulate individual weighing errors:

  • a) For 200 mg Atropine Sulphate:

  • rac{10mg}{200mg} imes 100 = 5 ext{%}

  • b) For 9.8 g Lactose:

  • rac{10mg}{9800mg} imes 100 = 0.102 ext{%}

  • c) For 1000 mg of the powder mix:

  • rac{10mg}{1000mg} imes 100 = 1.0 ext{%}

  • d) For 7 g of Lactose:

  • rac{10mg}{7000mg} imes 100 = 0.143 ext{%}

  • e) For 200 mg of powder mix 2:

  • rac{10mg}{200mg} imes 100 = 5 ext{%}

• Total individual error = 11.245% exceeds the allowable 10% for the formulation.

• Recommendations: Use a balance with a lower sensitivity (e.g., 1 mg) to reduce total error below 10%.

4.3 Practice Question 1: Propranolol Formulation

• Goals involve preparing 3 pediatric powders with Propranolol Hydrochloride 10 mg and Lactose 110 mg.

• Prepare one extra powder to allow for manipulation losses:

  • For 4 preparations, resulting formula: 10 mg Propranolol, 440 mg Lactose.

  • Measure MWM, weigh Propranolol, and dilute.

• Further calculations involved for accurately obtaining required proportions.

5. Ratio Strength and Dilution

5.1 Ratio Strength

• Concentration expressed as a ratio.

  • Example: 1:1000 means 1 g of solute in 1000 g of solution.

  • Conversion to mg/g: x = 0.001 g (or 1 mg) per g of powder mix.

5.2 Ratio Dilution

• Expresses how a formulation is diluted.

  • E.g., a cream diluted 1 in 10 means 1 g taken and made up to 10 g with a diluent.

6. Alligation Technique

• A method to determine proportions of two different strength products required to generate a desired strength in the final product.

  • Formula: ax + by = cx + cy

• Example: Mixing 20% Salicylic Acid with WSP to achieve 5% concentration involves deriving the correct parts of each to mix.

6.1 Practical Applications Using Salicylic Acid Formulations

• Example of mixing parts to achieve clinical specifications, calculating weights from part ratios:

  • WSP equation leading to desired quantities.

7. Miscellaneous Examples

7.1 Combining Formulations

• Example involving mixing various strengths of Salicylic Acid paste to achieve a target concentration.

7.2 Calculating Active Ingredient Requirements

• Examples where the amount of active ingredient needed for specific formulations is derived from known strengths and desired outcomes.

7.3 Concluding Remarks

• Whenever formulating, always ensure proper documentation and awareness of precision in measuring active and non-active ingredients. Adjustments and corrections might be needed based on balance sensitivity and calculated errors in practice.

• Practice Questions continue to apply all principles taught in the tutorial to real-world scenarios of pharmaceutical formulation.