The Pharmaceutics and Compounding Laboratory
Ointments: Preparation and
Evaluation of Drug Release

Laboratory Procedure

Evaluation of Ointment Bases

Describe the appearance and consistency (texture) of each ointment base. Rate spreadability as easy or difficult. Rate washability as washable or non-washable.

  1. Set aside at least 55 g to use next week in Step 4 below. Pack in a 2 oz. ointment jar.
  2. Take about 5 g of each ointment and note the appearance. Record your observations in Table I.
  3. Take a small amount of each preparation and slowly rub between your thumb and forefinger in order to gauge the consistency of the ointment. Record these observations in Table I.
  4. Finally, rub the remainder of the excess gently on the back of the hand. Note the ease with which each preparation spreads over the skin. After you judge spreading to be complete, the ointment base should be washed off with warm water. DO NOT USE SOAP. Record the ease of spreadability and washability in Table 1.

Table 1: Physical Properties of the Various Ointment Bases
  Appearance Consistency/texture Spreadability Washability
 
Base 1
 
       
 
Base 2
 
       
 
Base 3
 
       
 
Base 4
 
       
 
Base 5
 
       

Evaluation of Drug Release From Ointment Bases

While there is no doubt that the appearance of a topical product is important, the prime property of any medicated topical preparation is its ability to release drug in a reproducible manner. It is of little use to have a pharmaceutically elegant product that does not release drug. The release (diffusion) of a drug from a semi-solid system is dependent on the type of base into which the drug is incorporated as well as the solubility of the drug. Generally speaking, primarily oleaginous bases release substances slowly and unpredictably, since water cannot penetrate them sufficiently to dissolve the drug and allow for diffusion. Water miscible or primarily aqueous bases tend to release drugs more rapidly, especially drugs which are lipophilic and have a poor affinity for the hydrophilic base.

Once the drug has diffused from the base, the degree to which it is absorbed into the skin is influenced by several factors, including the area to which the ointment is applied, the condition of the skin (whether intact, denuded, or diseased), and the method of application.

  1. Each of the five bases should be used to prepare the following w/w ointment:
      Salicyclic acid 6%
      Base, qs 50 g

    For best results, the salicylic acid should be finely ground in a mortar, removed to an ointment slab, and levigated with 10 drops of glycerin (Base IV and V) or mineral oil (Bases I, II, and III) before being incorporated into the ointment base using geometric dilution.

  2. Each product is then filled into a one ounce ointment jar and the opening covered carefully with a piece of dialysis tubing of sufficient size to cover the jar. Secure the dialysis tubing around the neck of the jar and halfway down the body so as to ensure that water will not enter the jar. It is also important that no ointment escape from the jar. Any salicylic acid appearing on the distal surface of the dialysis tubing must therefore have permeated through the polymer membrane. Make sure that there are no air bubbles underneath the surface of the dialysis tubing. Be very careful not to damage or tear the dialysis tubing or to touch the outside surface of the dialysis tubing which is covering the ointment.



  3. In a 250 ml beaker, add 150 ml of distilled water at room temperature. Invert the sealed jar and immerse in the solution; record the time as time zero. Secure the ointment jar with a clamp so that the membrane is approximately ½ inch below the water level.



  4. Stir the solution gently but continuously with the stirring plate. Every five minutes for 45 minutes, remove approximately 5 ml, place into a cuvette and obtain the absorbance reading at 310 nm. Place the solution back into the beaker. Convert the absorbance reading into a concentration of salicylic acid using the standard curve. "Zero" the machine before each reading using water as a blank.

  5. Prepare a Beer's Law plot using the salicylic acid standards provided. Take 3 ml of each standard and read the absorbance at 310 nm. To zero the instrument, make a blank using 3 ml of water in lieu of any salicylic acid standard.

  6. Plot the amount of salicylic acid released as a function of time½ for the five preparations studied.

  7. Determine the release rates for the five products.

EXPERIMENTAL DATA AND RESULTS

Beer's Law Plot

1. Prepare a Beer's Law plot of the following salicylic acid standards: (attach graph)

SA Standard Absorbance @ 310 nm Regression Analysis
150 µg/ml _______________ intercept = _______
120 µg/ml _______________  
100 µg/ml _______________ slope = __________
80 µg/ml _______________  
50 µg/ml _______________ R2 = ____________
30 µg/ml _______________  
10 µg/ml _______________  

2. Record the release data for each of the five ointments in Table 2 and determine the rate of release of salicylic acid from each ointment base.

Evaluation of Drug Release

Base I

Time (minutes) Absorbance Concentration (µg/ml) Amount drug released (µg)
0 - - -
5      
10      
15      
20      
25      
30      
35      
40      
45      

 

Base II

Time (minutes) Absorbance Concentration (µg/ml) Amount drug released (µg)
0 - - -
5      
10      
15      
20      
25      
30      
35      
40      
45      

 

Base III

Time (minutes) Absorbance Concentration (µg/ml) Amount drug released (µg)
0 - - -
5      
10      
15      
20      
25      
30      
35      
40      
45      

Base IV

Time (minutes) Absorbance Concentration (µg/ml) Amount drug released (µg)
0 - - -
5      
10      
15      
20      
25      
30      
35      
40      
45      

 

Base V

Time (minutes) Absorbance Concentration (µg/ml) Amount drug released (µg)
0 - - -
5      
10      
15      
20      
25      
30      
35      
40      
45      

 

Plot the amount of salicylic acid released as a function of time½ for the five preparations studied. (attach graph). The slope of the line will be the release rate.

List the release rates for the five products.

Ointment Base Release Rate
Base I  
Base II  
Base III  
Base IV  
Base V  

 

Discussion

  1. Based on the physical properties of the various ointment bases studied, which ointment base would be most aesthetically acceptable to the patient. Explain.

  2. Which ointment base showed the most rapid release of salicylic acid? Explain why this might be.

  3. Which ointment base showed the slowest release of salicylic acid. Explain why this might be.

 


ADDITIONAL PRESCRIPTIONS FOR COMPOUNDING

                   Owen Mealot,MD       Rx# 61401

                   123 Upendown Rd.

                   Nowhere, NC 27000

Phone:  555-1234                   DEA# AH0079411



Name:   Ima Iching                Date:   Today  

Address:  123 Della Street        Phone: 555-5678

Rx

      

                               percent w/w

      Stearic Acid                   18.00   

      Potassium Hydroxide             0.52

       (supplied as a 12.5% aq. soln.)  

      Sodium hydroxide                0.18

       (supplied as a 1.2% aq. soln.)

      Cetyl alcohol                   0.50

      Glycerin                       18.05

      Methyl paraben                  0.15

      Purified water                 62.00

      Perfume     q.s.

      M.Ft. Foundation Cream



      Disp. 120 gm.



  Owen Mealot, MD                                   

  Product selection permitted    Dispense as written

  1. Melt the stearic acid and cetyl alcohol. Heat to 70°C.

  2. Dissolve the potassium hydroxide, sodium hydroxide, glycerin and methyl paraben in the purified water. Heat to 70°C.

  3. Add the aqueous phase to the melted oil phase slowly while stirring. Keep the oil phase on the hot plate while adding the aqueous phase.

  4. Remove product from hot plate. Allow to cool while stirring constantly, but slowly. Add perfume when cool.

Notes:

  1. 1. Glycerin Sp. gr. = 1.25
                  Owen Mealot,MD       Rx# 61402

                  123 Upendown Rd.

                  Nowhere, NC 27000

       Phone:  555-1234                   DEA# AH0079411



Name:   Ima Iching                Date:   Today  

Address:  123 Della Street        Phone: 555-5678

Rx

      

                               percent w/w

      Beeswax                        10.0   

      Mineral oil, light             50.0

      Purified water                 26.9

      Borax                           3.0

      Paraffin wax                    5.0

      Spermaceti                      5.0

      Methyl paraben                  0.1

      Perfume     q.s.

      M.Ft. Cold Cream      



      Disp. 120 gm.



  Owen Mealot, MD                                   

  Product selection permitted    Dispense as written

    1. Melt the beeswax, paraffin and spermaceti on a hot plate. Add the mineral oil and heat to 70°C.

    2. Dissolve the borax and methyl paraben in the water. Heat to 70°C.

    3. Add the aqueous phase to the melted oil phase slowly while stirring. Keep the oil phase on the hot plate while adding the aqueous phase.

    4. Remove product from hot plate. Allow to cool while stirring constantly, but slowly. Add perfume when cool.

    Notes:

    1. Light mineral oil Sp. gr. = 0.85

    2. Borax is sodium borate, decahydrate
                       Owen Mealot,MD       Rx# 61403
    
                       123 Upendown Rd.
    
                       Nowhere, NC 27000
    
        Phone:  555-1234                   DEA# AH0079411
    
    
    
    Name:   Ima Iching                Date:   Today  
    
    Address:  123 Della Street        Phone: 555-5678
    
    Rx
    
          
    
                                   percent w/w
    
          Cetyl alcohol                    1.5   
    
          Lanolin                          3.00
    
          Stearic acid                     3.00
    
          Glycerin                         7.0
    
          Triethanolamine                  2.25
    
           (supplied as a 10% aq. soln.)
    
          Methyl paraben                   0.10
    
          Purified water                  83.15
    
          Fragrance     q.s.
    
          M.Ft. Hand lotion
    
    
    
          Disp. 120 gm.
    
    
    
      Owen Mealot, MD                                   
    
      Product selection permitted    Dispense as written
    
    
    1. Melt the cetyl alcohol, lanolin, and stearic acid. Heat to 70°C.

    2. Dissolve the glycerin, triethanolamine and methyl paraben in the water and heat to 70°C.

    3. Add the aqueous phase to the melted oil phase slowly while stirring. Keep the oil phase on the hot plate while adding the aqueous phase.

    4. Remove product from hot plate. Allow to cool while stirring constantly, but slowly. When cool, add the fragrance.

    Notes:

    1. Glycerin Sp. gr. = 1.25

    Show the amount of each ingredient needed to compound 120 grams of the prescription.

    Stearic acid _____ g  
    Potassium hydroxide _____ g  
    (supplied as a 12.5% aq. soln.)   _____ ml
    Sodium hydroxide _____ g  
    (supplied as a 1.2% aq. soln.)   _____ ml
    Cetyl alcohol _____ g  
    Glycerin _____ g _____ ml
    Methyl paraben _____ g  
    Purified water _____ g _____ ml

     

    Beeswax _____ g  
    Mineral oil, light _____ g _____ ml
    Purified water _____ g _____ ml
    Borax _____ g  
    Paraffin wax _____ g  
    Spermaceti _____ g  
    Methyl paraben _____ g  

     

    Cetyl alcohol _____ g  
    Lanolin _____ g  
    Stearic acid _____ g  
    Glycerin _____ g _____ ml
    Triethanolamine _____ g  
    (supplied as a 10% aq. soln.)   _____ ml
    Methyl paraben _____ g  
    Purified water _____ g _____ ml