Stability of an Alcohol-free, Dye-free Hydrocortisone (2 mg/mL) Compounded Oral Suspension.

The stability of hydrocortisone in a commercially available dye-free oral vehicle was monitored to establish a beyond-use date for hydrocortisone oral suspension 2 mg/mL. Hydrocortisone oral suspension (2 mg/mL) was prepared from 10-mg tablets in a dye-free oral vehicle (Oral Mix, Medisca) and stored at 4°C and 25°C for 90 days in amber, plastic prescription bottles and oral syringes. The suspendability and dose repeatability of the oral suspension were evaluated. The solubility of hydrocortisone in the dye-free vehicle was determined. Over 90 days, pH and concentration of hydrocortisone in the oral suspension were measured. The stability-indicating nature of a high-pressure liquid chromatographic assay was evaluated in detail. The solubility of hydrocortisone in the dye-free vehicle was 230 mcg/mL at 25°C. This means that about 90% of the drug remains in the solid state where it is less susceptible to degradation. The preparation suspended well to support dose repeatability. The chromatographic assay resolved hydrocortisone from cortisone, excipients in the vehicle, and all degradation products. The assay passed United States Pharmacopeia system suitability tests. Hydrocortisone oral suspension (2 mg/mL) compounded using a dye-free, alcohol-free oral vehicle, Oral Mix, was stable in amber plastic bottles and syringes stored at 4°C and 25°C for 90 days within a 95% confidence interval.

Stability of Prednisone in Oral Mix Suspending Vehicle.

The stability of prednisone (5 mg/mL) formulated as a suspension in Oral Mix vehicle was evaluated. Oral Mix is a novel oral, dye-free suspending vehicle developed by Medisca Pharmaceutique Inc. for preparation of extemporaneous dosage forms. This drug was chosen based on its high frequency of prescription among the pediatric population. Suspensions were prepared from both pure active and commercial tablets utilizing two different container closures: amber glass bottles and polypropylene syringes (PreciseDose Dispenser Medisca Pharmaceutique Inc.). Formulations were stored at 5°C or 25°C and organoleptic properties, pH, and concentration were evaluated at predetermined time points up to 90 days. Validated stability-indicating high-performance liquid chromatography methods were developed. Beyond-use date was evaluated by statistical analysis of the overall degradation trend. Prednisone was stable for at least 90 days at 25°C. No changes in organoleptic properties or pH were observed for either of the formulations, and the global stability was roughly equivalent and sometimes superior to the stability of the same drugs in other previously used vehicles. Thus, Oral Mix was found to be a suitable dye-free vehicle for extemporaneous formulations.

Standards of practice, professional judgment, and scientific evidence to establish and extend a beyond-use date.

The establishment of both a beyond-use date and the extension of a beyond-use date need to be scientifically based. What is accepted as scientific evidence is at times misleading. The pharmacist may have the right to utilize some degree of professional judgment in both establishing and extending a beyond-use date, after a review of appropriate scientific literature. Notwithstanding this scientific review, it is the concept of professional judgment that seemingly needs to be better defined. A new-found appreciation for professional judgment will bring us to the understanding that a validated stability-indicating assay is the correct manner in which to extend a beyond-use date. This article addresses and discusses the recommendations and rigor required to establish and extend a beyond-use date. The perspectives of the pharmacist and physician are explored, as well as the impact of an extended beyond-use date, or lack thereof, are discussed. The application of a set of fundamental principles will be revealed, which will lead to finite conclusions as to the necessary methodology to establish as well as extend a beyond-use date.