Physicochemical stability of compounded midazolam capsules over a one-year storage period

Abstract Objectives In patients suffering from chronic liver disease, the hepatic metabolism of drugs is perturbed and the metabolic capacity is difficult to assess. Midazolam could be used as a phenotypical probe to predict the metabolic capacity of CYP3A to adjust dosages of drug substrates of this cytochrome. In this context, a prospective clinical trial is going to be conducted in our institution and a hospital preparation of midazolam capsules suitable for the clinical trial was developed. The objective of the present work was to assess the physicochemical stability of the formulation over 12 months to set shelf life. Methods Three batches of 1 mg capsules were prepared using midazolam hydrochloride and microcrystalline cellulose as a diluent. The capsules were stored at ambient temperature and protected from light. To measure the evolution of the capsules content, a stability-indicating high-performance liquid chromatography (HPLC) method was developed with ultraviolet (UV) detection at 254 nm. Data were confirmed using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical method. Results After one year, midazolam hydrochloride content remained higher than 95% of the initial concentration in capsules. Conclusions The results show that 1 mg midazolam capsules are stable for 12 months at room temperature and under dark conditions.

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Corn Bioethanol Side Streams: A Potential Sustainable Source of Fat-Soluble Bioactive Molecules for High-Value Applications

Foods ◽

10.3390/foods9121788 ◽

2020 ◽

Vol 9 (12) ◽

pp. 1788

Author(s):

Gabriella Di Lena ◽

Jose Sanchez del Pulgar ◽

Ginevra Lombardi Boccia ◽

Irene Casini ◽

Stefano Ferrari Nicoli

Keyword(s):

Liquid Chromatography ◽

High Performance ◽

Corn Oil ◽

Lipid Fraction ◽

Bioactive Molecules ◽

Array Detector ◽

Thin Stillage ◽

Dry Grind ◽

Liquid Chromatography Tandem Mass ◽

One Year

This paper reports data from a characterization study conducted on the unsaponifiable lipid fraction of dry-grind corn bioethanol side streams. Phytosterols, squalene, tocopherols, tocotrienols, and carotenoids were quantified by High Performance Liquid Chromatography with Diode-Array Detector (HPLC-DAD) and Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) in different lots of post-fermentation corn oil and thin stillage collected from a bioethanol plant over a time-span of one year. Fat-soluble bioactives were present at high levels in corn oil, with a prevalence of plant sterols over tocols and squalene. Beta-sitosterol and sitostanol accounted altogether for more than 60% of total sterols. The carotenoid profile was that typical of corn, with lutein and zeaxanthin as the prevalent molecules. The unsaponifiable lipid fraction profile of thin stillage was qualitatively similar to that of post-fermentation corn oil but, in quantitative terms, the amounts of valuable biomolecules were much lower because of the very high dilution of this side stream. Results indicate that post-fermentation corn oil is a promising and sustainable source of health-promoting bioactive molecules. The concomitant presence of a variegate complex of bioactive molecules with high antioxidant potentialities and their potential multifaceted market applications as functional ingredients for food, nutraceutical, and cosmeceutical formulations, make the perspective of their recovery a promising strategy to create new bio-based value chains and maximize the sustainability of corn dry-grind bioethanol biorefineries.

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Physicochemical stability of carfilzomib (Kyprolis®) containing solutions in glass vials, ready-to-administer plastic syringes and infusion bags over a 28-day storage period

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155217735881 ◽

2017 ◽

Vol 25 (2) ◽

pp. 339-350

Author(s):

Sun Hee Kim ◽

Irene Krämer

Keyword(s):

High Performance Liquid Chromatography ◽

Liquid Chromatography ◽

High Performance ◽

Room Temperature ◽

Visual Inspection ◽

Storage Period ◽

Reversed Phase ◽

Profound Knowledge ◽

Physicochemical Stability ◽

Study Results

Centralized aseptic preparation of ready-to-administer carfilzomib containing parenteral solutions in plastic syringes and polyolefine (PO) infusion bags needs profound knowledge about the physicochemical stability in order to determine the beyond-use-date of the preparations. Therefore, the purpose of this study was to determine the physicochemical stability of carfilzomib solution marketed as Kyprolis® powder for solution for infusion. Reconstituted solutions and ready-to-administer preparations of Kyprolis® stored under refrigeration (2–8℃) or at room temperature (25℃) were analyzed at predetermined intervals over a maximum storage period of 28 days. Chemical stability of carfilzomib was planned to be determined with a stability-indicating reversed-phase high-performance liquid chromatography assay. Physicochemical stability was planned to be determined by visual inspection of clarity and color as well as pH measurement. The study results show that reconstituted carfilzomib containing parenteral solutions are stable in glass vials as well as diluted solutions in plastic syringes and PO infusion bags over a period of at least 28 days when stored light protected under refrigeration. When stored at room temperature, reconstituted and diluted carfilzomib solutions are physicochemically stable over 14 days and 10 days, respectively. The physicochemical stability of carfilzomib infusion solutions allows cost-saving pharmacy-based centralized preparation of ready-to-administer preparations.

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Stability Determination of an Extemporaneously Compounded Ambrisentan Suspension by High Performance Liquid Chromatography Analysis

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-26.3.265 ◽

2021 ◽

Vol 26 (3) ◽

pp. 265-270

Author(s):

Jesse Cramer ◽

Mackenzie Bevry ◽

Stephanie Handler ◽

Kathryn Tillman ◽

Ehab A. Abourashed

Keyword(s):

High Performance Liquid Chromatography ◽

Liquid Chromatography ◽

High Performance ◽

Hplc Analysis ◽

Room Temperature ◽

Storage Period ◽

Storage Conditions ◽

Reversed Phase ◽

Hplc Method ◽

Fluorescent Light

OBJECTIVE Ambrisentan, an endothelin receptor antagonist FDA-approved for the treatment of pulmonary arterial hypertension in adult patients, lacks an acceptable pediatric dosage form. The objective of this investigation was to determine the stability of an extemporaneously compounded ambrisentan suspension. METHODS Ambrisentan suspension was compounded to a concentration of 1 mg/mL using commercially available suspending agents. The suspension was then evenly split into 2 plastic amber prescription bottles. One bottle was stored at room temperature and under continuous fluorescent light while the other bottle was stored under refrigeration and protection from light. A fast and selective reversed-phase high-performance liquid chromatography (HPLC) method was developed and validated for the analysis of ambrisentan. HPLC analysis was performed on samples withdrawn from the stock bottles at predetermined time intervals, up to 90 days. RESULTS The developed HPLC method enabled the elution and detection of ambrisentan peak at 4.4 minutes. HPLC analysis revealed that all samples from both storage conditions retained >90% potency throughout the study timeframe. There were no signs of any ambrisentan breakdown products on HPLC analysis. Color and odor of the final product was also consistent throughout the 90-day storage period. CONCLUSION Ambrisentan suspension, compounded to 1 mg/mL, is stable at room temperature or under refrigeration for up to 90 days.

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