Development of a topical suspension containing three active ingredients.
The objective of this study was to develop a topical suspension that contains sarafloxacin hydrochloride (1 mg/mL), triamcinolone acetonide (1 mg/mL), and clotrimazole (10 mg/mL), and is stable at room temperature (15-28 degrees C) for clinical usage. Due to the difference in the physicochemical properties and chemical stability profiles of these three active ingredients, it is a challenge to develop a stable suspension formulation containing these three drugs. In this study, the stability of these drugs in different buffer solutions was determined under different accelerated isothermal conditions. The Arrhenius equation was subsequently utilized to predict the room-temperature stability of these three drugs in these buffer solutions. By knowing the room-temperature solubility of the drugs in the buffer solution, the stability of the drugs in suspension was predicted. As a result, a 0.02 M phosphate buffer (pH 7.0) containing 0.02% (w/v)polysorbate 20, 1% (w/v) NaCl, and 0.1% (w/v) EDTA was determined to be an acceptable medium. In addition, 0.35% (w/v) high-viscosity carboxymethylcellulose (HV-CMC) was first selected as the suspending agent to enhance the redispersibility of the suspension. Stability data further supported that all three drugs were stable in the suspension containing HV-CMC with less than 5% potency loss for at least 6 months at 40 degrees C and 12 months at 25 degrees C. However, the viscosity drop of this HV-CMC formulation at 25 degrees C and 40 degrees C became a product stability concern. To improve the viscosity stability of the suspension, the medium-viscosity carboxymethylcellulose (MV-CMC) was selected to replace the HV-CMC as the suspending agent. The optimal combination of MV-CMC and sodium chloride in achieving the most desirable dispersion properties for the formulation was determined through the use of a 32 factorial design. The optimal formulation containing 1% MV-CMC and 1% sodium chloride has shown improved viscosity stability during storage and has been used for clinical studies.
Chang
H C
HC
Hospital Products Division, Abbott Laboratories, Abbott Park, IL 60064-3500, USA.
Li
L C
LC
Toongsuwan
S
S
Stephens
D
D
Liu
R M
RM
Plichta-Mahmoud
H
H
D000287:Administration, Topical; D000890:Anti-Infective Agents / Q000737:chemistry*; D002021:Buffers; D002939:Ciprofloxacin / Q000031:analogs & derivatives* / Q000737:chemistry*; D003022:Clotrimazole / Q000737:chemistry*; D004338:Drug Combinations; D004339:Drug Compounding; D004355:Drug Stability; D005079:Excipients; D024841:Fluoroquinolones; D012996:Solutions; D013535:Suspensions; D013696:Temperature; D013997:Time Factors; D014222:Triamcinolone Acetonide / Q000737:chemistry*
D000890:Anti-Infective Agents; D002021:Buffers; D004338:Drug Combinations; D005079:Excipients; D024841:Fluoroquinolones; D012996:Solutions; D013535:Suspensions; D002939:Ciprofloxacin; D014222:Triamcinolone Acetonide; D003022:Clotrimazole; C047224:sarafloxacin