A survey of Top 200 Drugs—Inconsistent Practice of Drug Strength Expression for Drugs Containing Salt Forms

Many ionizable drugs are developed and marketed as salt forms. However, there are no clear US regulatory guidelines on drug strength labeling for salts. The strengths of some drugs are expressed as salts and some as free acids/bases. This study surveyed the top 200 US drugs to assess the common practice in industry. The top 200 drugs prescribed in the United States were included in this survey. The drugs containing active pharmaceutical ingredient (API) salts were selected for analysis. Generic or combination products with redundant API salts were excluded. The package insert of each selected drug was reviewed, and the information on drug strength expression was extracted and categorized. Out of the top 200 drugs, 59 unique API salts were identified. The drug strengths were expressed as salts for 32 drugs (54%) and as free acids/bases for 27 drugs (46%). The survey results revealed the inconsistent practice among the industries regarding the drug strength expression for salts. Non-harmonized labeling practice can lead to confusions, potential calculation/dosing errors, and complications in labeling new products. The authors recommend the US Food and Drug Administration to standardize the labeling format for salts and preferably express the drug strengths based on the free acid/base forms. © 2011 Wiley Periodicals, Inc. and the American Pharmacists Association

Stability of levetiracetam oral solution repackaged in oral plastic syringes

Purpose The long-term stability of levetiracetam solution in oral syringes was investigated in order to define a suitable beyond-use date and demonstrate the feasibility of storing prepared syringes for extended periods as an alternative to commercial levetiracetam unit dose cups. Methods Levetiracetam oral solution (100 mg/mL) was drawn into 1- and 10-mL amber polypropylene oral syringes. Triplicate samples of the syringe preparations were stored at refrigeration (2–8 °C) or room temperature (20–25 °C) and evaluated at monthly intervals for up to six months. At each time point, the samples were visually inspected and levetiracetam stability was assessed via pH measurement and high-performance liquid chromatography (HPLC). A short-term forced degradation study was conducted to confirm that the HPLC assay method was stability indicating. Results Over the six-month storage period, there was no significant change in either the visual appearance or pH of any of the levetiracetam samples. The results of serial HPLC assessment indicated that at least 97% of the initial levetiracetam concentration was retained in all samples of 1- and 10-mL oral syringes at both refrigeration and room temperature. Although this study was conducted using a generic product, the stability data obtained may be applied in repackaging decisions regarding other generic formulations of levetiracetam with similar excipient compositions. Conclusion Commercial levetiracetam 100-mg/mL oral solution was stable for up to six months in amber polypropylene oral syringes stored at both refrigeration and room temperature conditions

Formulation and Stability of an Extemporaneously Compounded Oral Solution of Chlorpromazine HCl

Chlorpromazine is a phenothiazine antipsychotic which is often used in hospice and palliative care to treat hiccups, delirium, and nausea. With the discontinuation of the commercial oral solution concentrate, there is a need to prepare this product by extemporaneous compounding. This study was initiated to identify an easy-to-prepare formulation for the compounding pharmacist. A stability study was also conducted to select the proper storage conditions and establish the beyond-use date. Chlorpromazine HCl powder and the Ora-Sweet® syrup vehicle were used to prepare the 100 mg/mL solution. Once the feasibility was established, a batch of the solution was prepared and packaged in amber plastic prescription bottles for a stability study. These samples were stored at refrigeration (2–8°C) or room temperature (20–25°C) for up to 3 months. At each monthly time point, the samples were evaluated by visual inspection, pH measurement, and high performance liquid chromatography (HPLC). A separate forced stability study was conducted to confirm that the HPLC method was stability indicating. A clear and colorless solution of 100 mg/mL chlorpromazine HCl was obtained by dissolving the drug powder in Ora-Sweet® with moderate agitation. The stability study results indicated that this solution product remained unchanged in visual appearance or pH at both refrigeration and room temperature for up to 3 months. The HPLC results also confirmed that all stability samples retained 93.6–101.4% of initial drug concentration. Chlorpromazine HCl solution 100 mg/mL can be compounded extemporaneously by dissolving chlorpromazine HCl drug powder in Ora-Sweet®. The resulting product is stable for at least three months in amber plastic prescription bottles stored at either refrigeration or room temperature

Stability of levetiracetam oral solution repackaged in oral plastic syringes

Purpose The long-term stability of levetiracetam solution in oral syringes was investigated in order to define a suitable beyond-use date and demonstrate the feasibility of storing prepared syringes for extended periods as an alternative to commercial levetiracetam unit dose cups. Methods Levetiracetam oral solution (100 mg/mL) was drawn into 1- and 10-mL amber polypropylene oral syringes. Triplicate samples of the syringe preparations were stored at refrigeration (2–8 °C) or room temperature (20–25 °C) and evaluated at monthly intervals for up to six months. At each time point, the samples were visually inspected and levetiracetam stability was assessed via pH measurement and high-performance liquid chromatography (HPLC). A short-term forced degradation study was conducted to confirm that the HPLC assay method was stability indicating. Results Over the six-month storage period, there was no significant change in either the visual appearance or pH of any of the levetiracetam samples. The results of serial HPLC assessment indicated that at least 97% of the initial levetiracetam concentration was retained in all samples of 1- and 10-mL oral syringes at both refrigeration and room temperature. Although this study was conducted using a generic product, the stability data obtained may be applied in repackaging decisions regarding other generic formulations of levetiracetam with similar excipient compositions. Conclusion Commercial levetiracetam 100-mg/mL oral solution was stable for up to six months in amber polypropylene oral syringes stored at both refrigeration and room temperature conditions

Stability of levetiracetam oral solution repackaged in oral plastic syringes

Objectives: With the increased use of levetiracetam oral solution in hospitals, there is a need to re-package this solution product in plastic oral syringes to facilitate dispensing and dosing. Without any stability data, these re-packaged syringes can only be assigned a maximum beyond-use date of 14 days when stored at controlled cold temperature based on USP. This study was designed to evaluate the long-term stability of levetiracetam solution in oral syringes for up to 6 months. Method: Commercially available levetiracetam oral solution (100 mg/mL) was drawn into 1-mL and 10-mL amber polypropylene oral syringes. The samples were stored at refrigeration (2-8°C) or room temperature (21-25°C), and they were pulled for evaluation at monthly intervals for up to six months. At each time point, the samples were evaluated by visual inspection, pH measurement, and high performance liquid chromatography (HPLC). A separate forced stability study was conducted to confirm that the HPLC method was stability indicating. Results: Over the period of 6 months storage, there was no significant change in visual appearance or pH for any of the levetiracetam stability samples. The HPLC results indicated that levetiracetam retained 97-108% of the initial concentration in 1-mL and 10-mL oral syringes at both refrigeration and room temperature. Implications: Commercial levetiracetam 100 mg/mL oral solution was stable for up to 6 months in amber polypropylene oral syringes stored at both refrigeration and room temperature conditions