Beyond-Use Date Study of 10% Miconazole and 10% Fluconazole

Separately Compounded in Humco RECURATM Topical Cream.

RECURATM BUD STUDY BUD996020.00 Page 1 of 4

10% MICONAZOLE AND 10% FLUCONAZOLE IN RECURATM

This document delineates all the analytical results to determine the beyond-use-date (BUD) of

two specific antifungal agents Miconazole (Free base) and Fluconazole individually compounded

with the concentration of 10% each in novel Humco’s topical vehicle (Humco, item # 996020) -

RECURA™. Stability of such formulations have been evaluated and determined the beyond-use

date. Two RECURATM formulations: Miconazole (10% w/w) and Fluconazole (10% w/w) were

separately compounded in Humco RECURATM anti-fungal topical cream in a bulk amount and

separated into several small jars and placed into the stability chamber at the normal conditions

(25 °C ± 2°C and 60 % ± 5% relative humidity).

The testing of both formulations (10% Miconazole and 10% Fluconazole in RECURATM) was

accomplished over the period of 0, 7, 14, 21, 28, 45,, 60, 90, and 180 days and showed that both

formulations are physically, chemically, and microbiologically stable for at least 180 days from

the date they compounded. Testing was accomplished as per the BUD testing protocol

(BUD996020) set forth for the comprehensive physical, chemical, and microbiological testing.

STUDY DESIGN

A detailed beyond-use date study design protocol was written where 180 days- BUD stability

study of two RECURATM antifungal topical cream formulations: Miconazole 10% (% w/w) -

free base and Fluconazole 10% (% w/w) was described in detailed. Identification of any jars was

in the specific order. For example: BUD996020_Formula 1_Jar#1 (Miconazole) and

BUD996020_Formula 2_Jar #1 (Fluconazole) etc.

PHYSICAL, CHEMICAL, AND MICROBIOLOGICAL TESTING

Preparation of Miconazole and Fluconazole Creams

Bulk amount (approximately 250 g) of each Miconazole 10% and Fluconazole 10% formulations

were prepared in RECURATM topical cream prior to dividing and putting those creams into 13

different polypropylene ointment jars (50 mL) with foiled lined caps for each formulations.

Samples from bulk batch was also divided into two unguator jars (30 mL) of each formulations.

Sample Testing and Testing Intervals

All BUD samples in the jars were placed in the calibrated stability chamber equilibrated to ICH

Controlled Room Temperature 25°C ± 2oC / 60% RH ±5%. Samples for BUD analysis were

Final Report - Beyond-Use Date Study of 10% Miconazole and 10%

Fluconazole Separately Compounded in Humco RECURATM Topical Cream.

RECURATM BUD STUDY BUD996020.00 Page 2 of 4

fully tested for all the listed requirements at following time points: 0, 7, 14, 21, 28, 28, 45, 60,

90, and 180 days. At each time-points, both formulations of RECURATM jars were taken out

from the stability chamber and let it equilibrate at the room temperature. Jars were weighed to

determine the weight loss (evaporation) during that time periods. Samples in the jars were

evaluated for physical form, feel and/or separation prior to mix the sample with glass rod.

Additionally, the potency of both formulations was also carried out for the sample in the

unguator jar to determine if the container permeation has any effect on the product over time (at

day 14 and day 28).

For microbiological stability, jars of both formulations were submitted to the HUMCO quality

control microbiological laboratory at day 0 and day 180. Four different microbiological tests

including: Total Aerobic Microbial Count (as per USP<61>), Total Combined Yeast and Mold

(as per USP<61>), Staphylococcus aureus and Pseudomonas aeruginosa (both as per USP<62>)

were conducted and reported the results.

All the sample jars for both formulations were tested as per the test sheet at given time points and

generated the data.

CONCLUSIONS

Two anti-fungal agents Miconazole 10% and Fluconazole 10%, compounded separately in

Humco RECURATM Formulation, were analyzed different time points: 0, 7, 14, 21, 28, 45, 60,

90, and 180 days. No significant changes in appearance, odor, feel were observed during the

beyond-use date study period. Both formulations’ pH, viscosity, and density also met the

protocol criteria set prior to the analysis. Miconazole and Fluconazole in RECURATM topical

cream formulations are hence considered physically stable over the beyond-use date period -180

days. Analytical quantification of Miconazole and Fluconazole actives in RECURATM Cream by

High Performance Liquid Chromatography showed that the products are within the acceptable

specification (label claim: 90% - 110%) and therefore these two formulations are chemically

stable over the 180 day period. Additionally, microbiological testing of Total Aerobic Microbial

Count, Total Yeast and Mold, S. aereus and P. aeruginosa course of the 180 days period under

normal conditions (25°C and 60% RH). Hence, two antifungal agents: Miconazole and

Fluconazole are physically, chemically, and microbiologically stable in the novel compounding

vehicle RECURATM for at least 180 days.

Beyond-Use Date Study of 10% Miconazole and 10% Fluconazole Separately Compounded in Humco

RECURATM Topical Cream.

RECURATM BUD STUDY BUD996020.00 Page 3 of 4

SUMMARY RESULTS – MICONAZOLE 10% IN RECURATM:

Beyond-use date results summary of Miconazole 10% in RECURATM formulation.

BUD Testing Results

Test Method DAY 0 Day 7 Day 14 Day 21 Day 28 Day 45 Day 60 Day 90 Day 180

Description/Physical

Form/Odor Organoleptic Pass Pass Pass Pass Pass Pass Pass Pass Pass

Feel Tactile Pass Pass Pass Pass Pass Pass Pass Pass Pass

Miconazole Assay

% Label Claim Humco 100.80% 99.54% 100.80% 101.40% 100.86% 104.03% 101.71% 97.20% 107.95%

pH (neat) USP <791> 8.31 8.73 8.85 9.28 9.10 9.25 9.03 8.85 8.85

Viscosity (F@2.5) USP <912> 212,600 195,000 155,000 159,000 133,000 143,000 175,000 195,000 175,100

Weight Loss Humco N/A 0.40 0.00 0.00 0.00 0.42 0.44 0.48 0.38

Density (in g/mL) USP <841> 1.08 1.07 1.06 1.07 1.08 1.08 1.08 1.07 1.10

Total Aerobic

Microbial Count USP<61> 0 - - - - - - - 0

Total Combined

Yeast & Mold USP<61> 0 - - - - - - - 0

Absence of

Staphylococcus

aureus

USP<62> Absent - - - - - - - Absent

Absence of

Pseudomonas

aeruginosa

USP <62> Absent - - - - - - - Absent

Beyond-Use Date Study of 10% Miconazole and 10% Fluconazole Separately Compounded in Humco RECURATM Topical Cream.

RECURATM BUD STUDY BUD996020.00 Page 4 of 4

SUMMARY RESULTS – FLUCONAZOLE 10% IN RECURATM:

NOTE: Comprehensive BUD Report is Available Upon Request.

Beyond-use date results summary of Fluconazole 10% in RECURATM formulation.

BUD Testing Results

Test Method DAY 0 Day 7 Day 14 Day 21 Day 28 Day 45 Day 60 Day 90 Day 180

Des./Physical

Form/Odor Organoleptic Pass Pass Pass Pass Pass Pass Pass Pass Pass

Feel Tactile Pass Pass Pass Pass Pass Pass Pass Pass Pass

Fluconazole Assay

% Label Claim

Humco

Method 99.30% 98.37% 100.63% 101.82% 103.39% 107.40% 100.17% 102.32% 106.18%

pH (neat) USP <791> 8.18 8.80 8.69 8.95 9.15 9.26 8.98 8.75 8.68

Viscosity (F@2.5),

cps USP <912> 218,000 187,000 195,000 174,000 161,000 192,000 210,000 185,000 159,000

Weight Loss (g) Humco

Method N/A 0.3 0 0 0.2 0.57 0.42 0.4 0.06

Density (g/mL) USP <841> 1.08 1.07 1.07 1.07 1.08 1.09 1.08 1.09 1.1

Total Aerobic

Microbial Count USP<61> 0 N/A N/A N/A N/A N/A N/A N/A 0

Total Combined

Yeast & Mold USP<61> 0 N/A N/A N/A N/A N/A N/A N/A 0

Absence of

Staphylococcus

aureus

USP<62> Absent N/A N/A N/A N/A N/A N/A N/A Absent

Absence of

Pseudomonas

aeruginosa

USP <62> Absent N/A N/A N/A N/A N/A N/A N/A Absent