Secundum Artem - Perrigo

1 VOLUME 16 NUMBER 1. Secundum Artem Current & Practical Compounding Information for the Pharmacist. An ongoing CE Program provided by a grant from Perrigo Pharmaceuticals Stability of Extemporaneously Prepared Oral Liquid Formulations - Part VII. GOALS AND OBJECTIVES. Goal: To provide information from the peer-reviewed literature on stability studies of oral liquids. Objectives: After reading and studying the article, the reader will be able to: 1. List specific issues to be addressed in reviewing stability studies, 2. Describe the aspects of a stability-indicating assay that should be present in a stability study, 3. Analyze the tabulated results and assign an appropriate beyond-use date, and 4.

2 Discuss the conditions commonly used in stability studies for extemporaneously compounded preparations. INTRODUCTION least one intermediate, and a final time point to aid in In evaluating stability studies for appropriateness, it is evaluation; additional reasonable intervals are recom- important to check for specific topics to be addressed in mended. Samples should be prepared at least in the studies. A cardinal rule is that one of similar educa- triplicate. The storage conditions for the samples must be tion and ability should be able to reproduce the results described. Most commonly, room and refrigerated tem- from the information provided in the published study.

3 Peratures are used. It is of value to provide the actual Some specific issues to address in stability studies of temperatures. extemporaneous compounded preparations are as fol- lows. The analytical method must be stability-indicating and appropriate for the study. The stability-indicating nature The complete composition and method of preparation of of the assay is usually done by force-degrading samples the formula must be presented. It is interesting that to about 50-75% loss of drug using a combination of heat, many studies in the medical literature about new formu- light, oxidizing agent, acid and/or base methods. The lations or new drugs don't provide the complete degradants should be well-separated from the intact drug formulation information.

4 Fortunately, most stability for the study to be valid. Chromatograms should be pro- studies in the pharmaceutical literature now provide this vided of both intact and degraded drug. information. The shortfall would be if nondescript ingre- dients such as cherry syrup are used without any The manufacturer and lot number of all ingredients qualifying information. Commercial products, such as should be provided. The ingredients used must be at Ora-Sweet , are defined compositions and make it much least of USP or NF quality, if applicable. The equipment easier. manufacturer and model should be specified; supplies should be well-described. The data on the calibration The study design should have an initial (time-zero), at curve linearity, limit of quantification of the analyte, Loyd V.

5 Allen, Jr., , Quest Educational Services Inc. is accredited by the Professor Emeritus, University of Oklahoma College of Pharmacy Accreditation Council for Pharmacy Education as a Editor in Chief, International Journal of Pharmaceutical Compounding provider of continuing pharmacy education.. Dr. Allen is not affiliated with Perrigo Pharmaceuticals ACPE No. 748-0000-10-001-H04-P ( CEU). The initial release for this lesson is 05/01/10. This lesson is no longer valid for CE credit after 05/01/13. Disclaimer The content and opinions of this article are those of the author and are for educational purposes only. Although the material is based on review of multiple sources of information, it is not all inclusive of information available.

6 Readers should review and consider other publications and materials on this topic and not rely solely upon the information in this article. 5/5/10 9:16 AM Page 2. method of repeatability, intraday and interday coeffi- The mean pH values for the samples stored at room tem- Clozapine (C18H19 ClN4, MW Clozaril ) occurs sodium, hypromellose, lactose, magnesium stearate, poly- cients of variation should be provided. Analytical perature and refrigerator were pH ( ) and ethylene glycol, polysorbate 80, pregelatinized starch, Lansoprazole (C16H14F3N3O2S, MW , Pre- Table 7: Stability of lansoprazole 3 mg/mL in a mix- replicates should not exceed a variation of 2% and any ( ), respectively.)

7 The oral suspension under condi- as a yellow, crystalline powder that is soluble in alcohol and insoluble in water. It is an antipsychotic drug that is synthetic red iron oxide, titanium dioxide and white wax. vacid ) is a proton pump inhibitor that occurs as a ture of 1:1 sodium bicarbonate solution with unusual results should be adequately explained. tions in this study are stable for at least 90 days when They are printed with black ink, which contains lecithin, Ora-Plus:Ora-Sweet (1:1) packaged in glass bottles generically available. white to brownish-white powder that is practically refrigerated. pharmaceutical glaze, propylene glycol and synthetic black and stored at room and refrigerated temperatures.

8 Physical observations for any change in clarity (if a solu- insoluble in water. It is available as delayed-release tion), color, and for suspensions, any change in settling, Clozapine 20 mg/mL suspension was prepared by sus- iron capsules that also contain hydroxypropyl cellulose, Table 2: Stability of aprepitant 20 mg/mL in Ora-Blend pending clozapine in either Ora-Sweet, Ora-Plus or a low substituted hydroxypropyl cellulose, colloidal % Initial Concentration Remaining caking, resuspending, and for emulsions, creaming, layer- in glass and PET bottles stored at 4 C and 23 C. ing, etc. Generally, the proposed beyond-use-date (BUD) 1:1 mixture of Ora-Sweet and Ora-Plus and packaged in The suspension was prepared by thoroughly crushing the silicon dioxide, magnesium carbonate, methacrylic Time (days) Ref Temp Room Temp shows less than about a 7% loss.

9 The appropriate BUD is low-density polyethylene (LDPE) amber containers and dolasetron mesyltate tablets in a glass mortar. Ora-Plus and acid copolymer, starch, talc, sugar spheres, sucrose, % Initial Concentration Remaining stored at room temperature. Sampling was done initial- polyethylene glycol, polysorbate 80 and titanium 0 ( )a ( )a no longer than the length of the study. Any conclusions strawberry syrup or Ora-Plus with Ora-Sweet SF (1:1) were do not over-extend the data and are reasonable. The ly and on days 3, 6, 14, 28 and 63. The stability of used as vehicles. The mixture was packaged in amber plas- dioxide. 7 Time 4 C: 4 C 23 C 23 C. source of the drug must be specified; is it the bulk drug (days) Glass PET Glass PET clozapine under conditions in this study was deter- tic bottles and stored at refrigerated and room temperatures.

10 14 substance, capsules, tablets, injections, etc. as mined to be 63 days at room Sampling was done initially and on days 7, 14, 30, 60 and Table 6: Stability granisetron hydrochloride 28 0 ( )a ( )a ( )a ( )a different excipients may affect the BUD. mg/mL in Ora-Sweet:Ora-Plus packaged in plastic 56 5 ( ) ( ) ( ) ( ) At least 98% of the initial concentration of dolasetron mesy- prescription bottles and stored at refrigerator and For this issue, the individual drugs and concentrations Table 4: Stability of clozapine 20 mg/mL in Ora-Sweet, 91 14 ( ) ( ) ( ) ( ) Ora-Plus or a 1:1 mixture of Ora-Sweet and Ora-Plus late remained throughout the 90 day study in all room temperatures.