Stabililty of omeprazole in syrspend sf alka (reconstituted)

Stability of Omeprazole in SyrSpend SF Alka
(Reconstituted)
Paul A. Whaley, BS
ABSTRACT
Mark A. Voudrie II, MS, PMP
omeprazole is used in the treatment of dyspepsia, peptic ulcer dis-
Bridget Sorenson, CAPM
ease, gastroesophageal reflux disease, laryngopharyngeal reflux, and
zollinger–ellison syndrome. omeprazole is marketed by Astrazeneca
under a number of names, most notably Prilosec and losec, as well as
INTRODUCTION
being available from a number of generic manufacturers. omeprazole is
available in both tablet and capsule form, with varying strengths of each.
The need for other administration options for those patients who can-
used in the treatment of dyspepsia, peptic not take tablets or capsules has led compounding pharmacies to seek
other alternatives. one possible alternative is the use of a suspending
ryngeal reflux (LPR), and Zollinger–Ellison agent to create an oral solution or suspension. In the past, this has been
syndrome.1 It is used to treat a wide range accomplished using a sodium bicarbonate solution as the vehicle. How-
of the patient population, including both ever, sodium bicarbonate/omeprazole combination imparts a bitter and
infant and geriatric patients. These two unpleasant taste. SyrSpend SF Alka (reconstituted) is a vehicle for mak-
groups in particular may experience dif-ficulty in swallowing whole capsules or ing a suspension which has a pleasant taste, thus increasing palpability
tablets. In the past, sodium bicarbonate and compliance. The objective of this study was to determine the stabil-
ity of omeprazole in SyrSpend SF Alka (for reconstitution). The studied
an oral solution. Sodium bicarbonate does sample was compounded into a 2-mg/ml suspension and stored in a
little to mask the bitter taste of omeprazole. low-actinic plastic prescription bottle at temperatures between 2oC and
8oC. Six samples were assayed at each time point out to 92 days by a
a sweetener masks the bitter taste and increases the palpability of omeprazole. stability-indicating high-performance liquid chromatography method.
The method was validated for its specificity through forced degradation
considering the treatment of infants, as the studies. The shelf life of this product is at least 92 days, based on data
collected when refrigerated and protected from light.
compliance. Some compounding vehicles contain alcohol and sorbitol. SyrSpend SF Alka (for reconstitution) (Fagron [formerly water was supplied by filtering deionized Gallipot], St. Paul, Minnesota) is a sorbi- MATERIALS AND METHODS water from a Millipore Elix through a Milli-
tol- and alcohol-free alkaline suspending Chemical Reagents
pore Simplicity (Billerica, Massachusetts). agent which could serve as an appropriate from Gallipot (Lot 0906145D12; St. Paul, Equipment and Chromatographic
Minnesota). High-performance liquid chro- The objective of this study was to exam- matographic (HPLC)-grade acetonitrile (Lot Conditions
ine the stability of omeprazole when pre- Two different types of HPLCs were used. pared in an oral suspension using SyrSpend Michigan), 85% phosphoric acid ACS-grade The first, used for validation and the stabil- SF Alka (for reconstitution). The suspen- ity study, was a Perkin Elmer 200-Series sion was stored in a low-actinic plastic prescription bottle at a concentration of (Lot 107148; Fisher Scientific, Pittsburgh, a quaternary gradient solvent delivery sys- 2 mg/mL under United States Pharmaco- peia (USP) refrigerated (2oC to 8oC) storage tahydrate (Lot B0131737; Acros Organics, conditions. Stability was assessed by per- Geel, Belgium), and octanesulfonic acid (Lot with a Peltier tray, 200-mcL sample loop, cent recovery studies performed at varying souri) were used in the study. HPLC-grade tem, used for forced degradation studies, was a Varian Prostar (Palo Alto, California) equipped with a tertiary gradient solvent The authors are affiliated with Dynalabs, LLC, St. Louis, Missouri. delivery system, a photodiode array detec- 164 International Journal of Pharmaceutical Compounding
tor (PDA), and an 84-vial programmable autosampler with a 100-mcL sample loop, fIgUre. plot of omeprazole concentration in syrspend sf alka (reconstituted).
and 250-mcL syringe. The Perkin Elmer HPLC was operated and data was collected using Perkin Elmer Totalchrom chroma-tography software, while the Varian HPLC used Galaxie chromatography software. The mobile phase for the HPLC method was buffer (50 mM phosphate), acetoni-trile, and Octanesulfonic acid (700 mL:300 mL:4.0999 g). The mobile phase’s pH was adjusted to 7.00 with 85% phosphoric acid and was delivered at 1.0 mL/min. Chro-matographic separation was achieved using a 150 × 4.6 mm Phenomenex (Tor-rence, California) Gemini C18 column with 5-mcm particle packing. The mobile phase was used as solvent in diluting the standard and assay preparations to 80 mcg/mL. The assay was monitored at 301 nm following a 10-mcL injection.
Note: Dashed lines represent upper and lower limits of Omeprazole specification. Validation of Forced-degradation
Studies to Determine Stability-
indicating Characteristics of
was added to the prescription bottle con- table 1. stability of omeprazole
the High-performance Liquid
taining the omeprazole powder. The bottle in reconstituted syrspend sf alka
Chromatographic Method
refrigerated (2oc to 8oc) for 90 days.
formly dispersed. The flask was stored at USP-controlled refrigerated temperature elapsed time
% recovery
assayed to determine the specificity of the (2oC to 8oC) for the stability study.
product produced during storage of an oral Stability Study
suspension. Omeprazole was diluted to 80 mcg/mL in a solution of acid (0.1M HCl), in addition to exposure to ultraviolet light each stressor varied due to the relative for stability. The sample was packaged in stability of omeprazole to each individual a low-actinic plastic prescription bottles labeled and the resolution (USP) was digitally controlled laboratory refrigera- determined between the degradant and the sidered full separation. Purity calculations initial (T=0), 9 days (T=9), 14 days (T=14), T=0 was set as the initial concentration zole peak using the controlled unstressed percent recovery assay. The stability of shows the data in terms of concentration Preparation of Omeprazole
and that the concentration of the suspen- the percent recovery with respect to T=0 Suspension Samples
(90%<[omeprazole]<110%) throughout the adding 1 mL of suspension with a volumet- to a plastic prescription bottle. SyrSpend stability indicating by forcibly degrading The average and standard deviation of all mL water per 6.43 g of SyrSpend SF Alka. replicate injections at each time point was used to calculate the percent recovery.
Omeprazole was stable to light, with slight International Journal of Pharmaceutical Compounding
Vol. 16 No. 2 | March/April 2012 165
table 2. summary of the validation parameters for the high-performance liquid
chromatographic method Used in the stability study of omeprazole in syrspend sf alka
heat. The degradants present in the acid (reconstituted).
validation parameter
able resolution. Additionally, validation parameters listed in Table 2 show that all system suitability results met acceptance Gallipot SyrSpend SF Alka
(Reconstituted) Omeprazole
Suspension
The initial potency of the omeprazole
TA B L E 2 . Summary of the Validation Parameters for the High-Performance
liquid Chromatographic Method Used in the Stability Study of Omeprazole in
SyrSpend SF Alka (Reconstituted).
script. This concentration was 102.4% of VAliDAtiOn PARAMEtER
the compounding target of 2 mg/mL. The T=0 result was set as the baseline for all other time points tested. The assay results showed an overall downward trend to a low point of 1.8635 mg/mL at T=92. Every rep- licate chromatogram for every time point was clear of degradant peaks and had the same chromatographic profile.
CONCLUSION
SF Alka (reconstituted) for 92 days when stored under refrigerated (2oC to 8oC) conditions. The sample was still within specification at day 92. However, the overall trend is that of decreasing con-centration during the course of the study. The beyond-use-date should be set to 60 days. The findings of this study show that SyrSpend SF Alka (reconstituted) is an acceptable suspending vehicle for prepar-ing individual compounded omeprazole formulations. This formulation has the added advantage of helping to mask the bitter taste while remaining alcohol and sorbitol free. The formulations would be viable alternatives to commercially avail-able capsules when that dosage form is found to be inappropriate.
REFERENCE
1. U.S. National Library of Medicine.
Address correspondence to Paul Whaley, BS, Omeprazole. [National Center for Bio- Method Development Chemist, Dynalabs, LLC, 2327 Chouteau Avenue, St. Louis, MO nih.gov/pubmedhealth/PMH0000936. Accessed January 16, 2012.
166 International Journal of Pharmaceutical Compounding

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