E-DRUG: Study of stability of medicines under tropical conditions
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Dear Colleagues,
We are planning a long term study of the stability (active ingredient content, dissolution and identification of any degradation products) of medicines in the laboratory and in a hot and humid tropical field environment. The FDA/ICH guidelines (FDA Q1A(R2) Stability Testing of New Drug Substances and Products. www.fda.gov/CbER/gdlns/ichstab.pdf) give useful information for planning such studies in the laboratory and recommend that three different batches should be tested. However, we have been unable to find any recommendations as to the sample size required and how many dosage units per batch, such as tablets, should be removed at each time point for assays. Sample size calculations will depend on inter-tablet variability in degradation - information which is unavailable for the medicines we hope to test. If you are aware of any guidelines on sample sizes for such experiments we would be very grateful for the information.
With very best wishes,
Paul Newton
Microbiology Laboratory
Mahosot Hospital
Vientiane, Lao PDR
e-mail: newtonpaul100@yahoo.co.uk
E-DRUG: Study of stability of medicines under tropical conditions (2)
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Dear Paul,
I think you should see the european guidelines on stability of finished
product and active substance, when the active substance is known. You
should also consider whether the active substance is included in a pharmacopoea.
I can give you the exact references of the guidelines if you are
interested.
Best wishes,
Elisabeth Lopez
ELM Pharmaceutical Consulting
C/ Balmes 110, 4º D
08008, Barcelona, Spain
Tel: + 34 932157195 / 609037890
Fax: + 34 932156030
www.elpharm.com
E-DRUG: Study of stability of medicines under tropical conditions (3)
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Dear Dr Paul Newton,
Studies on the stability of medicines under different storage conditions require careful planning from the beginning. You would not want to end your experiments halfway or be unable to perform additional experiments because insufficient samples were stored from time zero. Here are some of the factors our laboratory would consider in selecting the original number of samples to be put in stability:
- # of stability cdtns (e.g 25, 30 and 40 degrees celcius)
- # of time pts (e.g 0, 2 wks, 1 mth, 3 mth, 6 mth, 1 yr...)
- # of variables (e.g active ingredient, dissolution, preservative, degradation ...)
- # of batches
- # of samples per batch (usually 3)
- # injections on HPLC (if preferred method of analysis) per sample usually 3)
- ...
This number will also depend on how your sample preparation will be done. From each batch a number of tablets e.g 10 can be crushed together, from which 3 separate samples are prepared (each equivalent to mean wt of total tabs). This method gives you a more homogenous sample, however some active ingredient can be lost in the process e.g sticking to mortar bottom. Alternatively, from each batch the uniformity of mass test can be performed on the tablets. If it meets the requirements then individual tablets can be prepared as samples. Tablets will easily disintegrate in most solvents with slight shaking.
As you suggested, the ICH does not specify how the degration studies should be conducted and as the inherent degradation products of your samples are unknown, I will suggest you store extra samples for each time point for reasons mentioned in the ICH and in this text.
Hope this helps.
Magnus A. Atemnkeng PhD
Montreal, Canada
E-mail: magnusajong@yahoo.com
E-DRUG: Study of stability of medicines under tropical conditions (4)
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Dear Paul,
In addition to What Dr. Atemnkeng recommended, I suggest you also consider the following:
- What are your stability indicating tests ?
- If the drug you want to test has a monograph, this should give you a good idea about how many units you will need.
- Please refer also to pharmacopeias (e.g. General chapter <1150> Pharmaceutical stability of USP-31, 2008 p.613)
- Another good source of information is the manufacturer of the product or the regulatory authority of the country where that product is registered and where you want to carry the study. Information about stability of drugs are required to obtain Market Authorization.Good Luck with your study,
Best regards,
Karim Smine, Ph.D.
Head of Drug Regulation
Health Authority - Abu Dhabi
United Arab Emirates
E-mail: lahrizi65@hotmail.com