Stability of captopril in syrspend sf

Stability of Captopril in SyrSpend SF
Christine M. geiger, MS
ABSTRACT
Bridget Sorenson, BS, CAPM
Captopril is an angiotensin-converting enzyme inhibi-
Paul A. whaley, BS
tor available as a tablet. Patients who are unable to
take tablets have led compounding pharmacies to
seek alternative dosage forms including solutions
InTRODuCTIOn
and suspensions. The objective of this study was to
Captopril is an angiotensin-converting enzyme (ACE) inhibi- determine the stability of captopril in sorbitol-free,
tor used for the treatment of hypertension and congestive heart alcohol-free SyrSpend SF suspending agent. The
failure.1 Captopril is commonly marketed by Bristol-Myers studied samples were compounded into a 0.8-mg/ml
Squibb under the trade name Capoten and is available generically suspension and stored in low-actinic plastic bottles at
from several manufacturers. Captopril is available as tablets1 in temperatures between 2°C to 8°C. Six samples were
strengths of 12.5 mg, 25 mg, 50 mg, and 100 mg for oral adminis- assayed at each time point out to 32 days by a sta-
tration.2 Captopril is a white to off-white crystalline powder that bility-indicating high-performance liquid chromatog-
may have a slight sulfurous odor. An oral preparation containing a sweetener may increase the palatability of an oral dose form. Some raphy method. The samples remained within 90% to
patients are unable to use suspending agents containing sorbitol 110% of the initial concentration throughout day 14
or alcohol. SyrSpend SF (Fagron US [formerly Gallipot], St. Paul, of the study. based on the data collected, the beyond-
Minnesota) is an alcohol- and sorbitol- free suspending agent use date of these preparations is 14 days when pro-
which could serve as a suitable suspending agent for compounding tected from light and refrigerated.
captopril oral suspensions.
The objective of this study was to examine the stability of cap-topril in an oral suspension using SyrSpend SF. The suspension was stored in a low-actinic plastic bottle at a concentration of 0.8 ent solvent delivery system, a dual wavelength UV/VIS detec- mg/mL at refrigerated storage conditions. Stability was assessed tor, and a 100-vial programmable autosampler with a Peltier by percent recovery studies performed at varying time points tray, 200-mcL sample loop, and a 250-mcL syringe. The second HPLC system, used for forced degradation studies, was a Varian Prostar (Palo Alto, California) equipped with a tertiary gradient MATERIALS AnD METhODS
solvent delivery system, a photodiode array detector (PDA), and Chemical Reagents
an 84-vial programmable autosampler with a 100-mcL sample loop and a 250-mcL syringe. The Perkin Elmer HPLC was oper- Captopril powder (Lot AA14409-002569) was received from ated and data was collected using Perkin Elmer Totalchrom Fagron US [formerly Gallipot]. SyrSpend SF (Lot 1006242R14) chromatography software while the Varian HPLC used Galaxie also was received from Fagron US [formerly Gallipot]. High- chromatography software. The mobile phase for the HPLC method performance liquid chromatographic (HPLC)-grade methanol is 0.34% phosphoric, 2.63% tetrahydrofuran, 29.20% methanol, (Lot DF870; Honeywell, Muskegon, Michigan), 85% phosphoric and 68.14% water. The mobile phase was adjusted to a pH of acid (Lot 2011052000; CCI, Columbus, Wisconsin), and tetrahy- 2.6 with 85% phosphoric acid and was delivered at 1.2 mL/min. drofuran (Lot WW0200; Spectrum, Gardena, California) were Chromatographic separation was achieved using a 150 × 4.6 mm used in this study. HPLC-grade water was supplied by filter- Phenomenex (Serial No. 610040-9; Torrence, California) Gemini ing deionized water from a Millipore Elix through a Millipore C18 column with 5-mcm particle packing. The mobile phase was used as a solvent to dilute the standard and assay preparations to 50 mcg/mL. All preparations were filtered prior to injection. The Equipment and Chromatographic Conditions
assay was monitored following a 100-mcL injection.
Two different types of HPLCs were used. The first, used for validation and the stability study, was a Perkin Elmer 200-Series (Waltham, Massachusetts) equipped with a quaternary gradi- The authors are affiliated with Dynalabs, LLC, located in St. Louis, Missouri. 336 International Journal of Pharmaceutical Compounding
www.IJPC.com
Validation of Forced-Degradation Studies to
TA B L E 1 . Stability of Captopril in SyrSpend SF
Determine Stability-indicating Characteristics of
Refrigerated (2°C to 8°C) for 32 Days.
the high-performance Liquid Chromatographic
elapsed Time
% recovery
Captopril samples were stressed and assayed at 220 nm to determine the specificity of the HPLC method to any possible degradation product during storage of an oral suspension. Captopril was diluted to 50 mcg/mL in solutions of acid (0.1M HCl), base (0.1M NaOH), hydrogen peroxide (3.5%), in addition to exposure to ultraviolet light at 365 nm and heat at 70°C for F I g u R E . Plot of captopril concentration in SyrSpend SF
three hours. Any extraneous peaks found in the chromatogram suspension.
were labeled and the resolution (United States Pharmacopeia) was determined between the degradant and the captopril. Purity calculations were performed in Galaxie on the captopril peak using the controlled unstressed standard as a reference. Preparation of Captopril Suspension Samples
The captopril suspension was prepared by adding 100 mL of SyrSpend SF via volumetric pipette and 157.0 mg of captopril [Captopril] mg/mL 0.65
to a low actinic prescription bottle. Another 100-mL aliquot of SyrSpend SF was added to achieve a final concentration of 0.793 mg/mL captopril (concentration corrected for loss on drying and assay). The suspension was stored at refrigerated conditions Elapsed Time (days)
between 2°C to 8°C for the duration of the study.
Note: Dashed lines represent upper and lower limits of captopril specifications. Stability Study
The sample of captopril suspended in SyrSpend SF at a con-
centration of 0.7931 mg/mL was submitted for stability. The
DISCuSSIOn
sample was packaged in a low actinic plastic prescription bottle and stored at refrigerated conditions between 2°C to 8°C. Time The HPLC method was shown to be stability indicating by forc- points were initial (T=0), 12 days (T=12), 14 days (T=14), and 32 ibly degrading captopril and separating the degradant peaks from days (T=32). The evaluation parameter was percent recovery that of the main analyte. Captopril was stable to acid and light; assay. The stability of captopril in suspension was defined by the however, oxidizer and heat created some degradation. Base created percent recovery with respect to T=0 using the validated HPLC significant degradation. The degradants present were all separated method. The sample stock was prepared six times by adding 1 from the analyte with acceptable resolution. Additionally, valida- mL of suspension with a volumetric pipette to a 20-mL flask and tion parameters listed in Table 2 show that all system suitability diluting to volume with mobile phase. The average and standard deviation of all replicate injections at each time point were used to calculate the percent recovery.
TA B L E 2 . Summary of the Validation Parameters for the
high-performance Liquid Chromatographic Method used
in the Stability Study of Captopril.
The stability of captopril in SyrSpend SF is shown in Table validaTion parameTer
1. The result of 0.7808 mg/mL at T=0 was set as the initial con- centration for the study, and all subsequent time points were compared to this value. The Figure depicts the data in terms of concentration of the suspension that remained within the speci- Extraction precision (SyrSpend SF) n=6 % RSD = 1.44 fications (90%<[captopril]<110%) throughout the duration of International Journal of Pharmaceutical Compounding
Vol. 17 No. 4 | July/August 2013 337
The initial potency of captopril in SyrSpend SF suspension was 0.78081 mg/mL, which is shown in the Figure. This concentration was 98.45% of the compounding target of 0.793079 mg/mL. The T=0 result was set as the baseline for all other time points tested. The assay results varied between 0.67167 (T=32) and 0.78081 (T=0) for refrigerated conditions. All sample preparations at each time point were within specification with the exception of those at T=32, with a high relative standard deviation of 0.77% (T=32). Every replicate chromatogram for every time point was clear of degradant peaks and had the same chromatographic profile.
COnCLuSIOn
Captopril was stable in SyrSpend SF for 14 days when stored
under refrigerated conditions (2°C to 8°C) when compounded
from powder. The sample was still within specification at day 14;
therefore, the beyond-use date is concluded to be 14 days. By day
32, the sample was no longer within specifications. The findings of
this study show that SyrSpend SF is an acceptable oral syrup and
suspending vehicle for preparing individual captopril formula-
tions when stored refrigerated between 2°C to 8°C. This formula-
tion has the added advantage of helping to mask the bitter taste
while remaining alcohol, sorbitol, and sugar free. The formulation
would be a viable alternative to commercially available tablets
when that dosage form is found to be inappropriate.
REFEREnCES
1. MedlinePlus: A Service of the U.S. National Library
of Medicine, National Institutes of Health. Captopril. [MedlinePlus Website.] Updated as of October 15, 2012. Available at: meds/a682823.html. Accessed March 28, 2013.
2. RxList: The Internet Drug Index. Capoten (Captopril Tablets, USP). [RxList Website.] Updated as of October 9, 2012. Available at: Accessed March 28, 2013.
Address correspondence to Bridget Sorenson, BS, CAPM, 2327 Chouteau Avenue, Saint Louis, MO 63103. E-mail: [email protected] 338 International Journal of Pharmaceutical Compounding

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