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U.S. Department of Health and Human Services

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Stability and Dose Uniformity Evaluations of Doxycycline Solid Dosage Tablets Ground and Mixed in Food or Drinks

James F. Brower, Terry W. Moore, John C. Reepmeyer, Moheb M. Nasr and Lucinda F. Buhse,

U.S. Food and Drug Administration, Division of Pharmaceutical Analysis, 1114 Market St., Room 1002, St. Louis, MO 63101.

Government stockpiles of drugs needed for bioterrorism include solid dosage forms. In order to give these drugs to children in an emergency, the solid dosage forms need to be ground and mixed with appropriate food/drinks. To be effective in children, the drug/food or drug/drink mixture would need to have good stability and dose uniformity and have reasonable taste. For this study, stability and dose uniformity were examined for doxycycline tablets mixed with various foods/drinks. Tablets were ground and visibly divided into halves and quarters and mixed with low fat chocolate milk to determine dosage variability. Dose variability results are presented in Table 1.

Table 1: Dosage uniformity determination: analysis of crushed tablets mixed with low fat chocolate milk.

Dosage
(Mg)

Tablet Portion

# Replicates

Mg Doxycycline:
Average and SD

Mg Doxycycline:
Range

% Desired Dosage*:
Average

% Desired Dosage*:
Low

% Desired Dosage*:
High

100 Mg

1

3

96.1+/-0.6

95.6-96.7

99

99

100

75 Mg

¾

3

67.8+/-3.1

64.4-70.5

93

89

97

50 Mg

½

6

47.0+/-2.4

42.9-49.5

97

88

102

25 Mg

¼

12

23.8+/-3.5

18.3-32.1

98

75

132

 * % Desired Dosage based on an average tablet assay of 97% equating to 100% dosage.

Average dosages were found to be good for administration of ¼, ½, ¾ or one tablet (93%-99% of desired amount). The range of dosages was most variable for the ¼ tablet (75%-132% of desired amount). Analysis of five aliquots of a doxycycline tablet dissolved in low fat chocolate milk gave assays with a RSD% of 0.93% (n=5) which demonstrates a high degree of homogeneity of the doxycycline within the milk. Therefore, variability in the desired dosage is caused by the accuracy of visibly dividing the powder into two or four fractions.

Twenty-four hour stability [room temperature (22 - 26 ºC) and refrigerator (2 - 8 ºC)] of doxycycline added to each of the following preparations were evaluated: water, apple juice with table sugar, low fat milk, low fat chocolate milk, regular chocolate milk, chocolate pudding, grape jelly, and strawberry jelly. The result of recovery and stability testing of doxycycline mixtures are shown in Table 2.

Table 2: Recovery and stability of doxycycline (one crushed tablet) mixed with various foods/drinks

Foods/Drinks Original
% Recovery
% Recovery After 24 Hours:
Room Temperature
% Recovery After 24 Hours:
Refrigerator
Chocolate pudding

102

96

95

Chocolate milk

94

99

99

Low fat chocolate milk

96

99

99

Simple syrup with sour apple flavor

98

105

100

Apple juice

101

100

101

Low fat milk

102

104

104

Yogurt with cherry flavor

97

95

98

Strawberry jelly

95

99

101

Grape jelly

101

100

96

Water

101

102

103

Good original recoveries (all >94% recovery) and 24-hour stability (all >95% recovery) (refrigerated and room temperature) were seen for the doxycycline tablets crushed and mixed with all ten foods and drinks. In addition, doxycycline in low fat chocolate milk was found to be stable when refrigerated for 1 week (>98% recovery).

Crushed doxycycline tablets were stable (>95% recovery) for at least six days when wrapped in aluminum foil and stored at room temperature.