Drug formulations intended for the global market should be tested for stability under tropical climatic conditions.
OBJECTIVE
The quality of drugs imported into developing countries having a tropical climate may be adversely affected if their formulations have not been optimized for stability under these conditions. The present study investigated the influence of tropical climate conditions (class IV: 40 degrees C, 75% relative humidity) on the drug content, in vitro dissolution and oral bioavailability of different formulations of two essential drugs marketed in Tanzania: diclofenac sodium and ciprofloxacin tablets.


METHODS
Before and after 3 and 6 months storage under class IV conditions the drug content and in vitro dissolution were evaluated using United States Pharmacopoeia (USP) 24 methods. Following a randomized four-period cross-over study, the pharmacokinetic parameters of drug formulations stored for 3 months under class IV conditions were compared with those stored at ambient conditions.


RESULTS
Drug content and drug release from all tested ciprofloxacin formulations were within USP-24 requirements and remained stable during storage at simulated tropical conditions. Oral bioavailability was also not influenced by tropical conditions. The dissolution rate of two diclofenac formulations (Diclo 50 manufactured by Camden and Dicloflame 50 manufactured by Intas) reduced significantly during storage under class IV conditions. After oral administration Camden tablets stored for 3 months under class IV conditions showed a reduction in C(max) (90% CI of C(max) ratio: 0.59 - 0.76). This reduction was smaller than expected based on the in vitro tests.


CONCLUSIONS
Some drug formulations imported into Tanzania are not optimized for stability in a tropical climate. Manufacturers and regulatory authorities should pay more attention to the WHO recommendations for testing the stability of drugs under tropical climate conditions. Efforts should be made to improve the in vitro tests to better predict the bioavailability.
Risha
P G
PG
Department of Pharmaceutics, Faculty of Pharmacy, Muhimbili University College of Health Sciences, Dar es Salaam, Tanzania.
Vervaet
C
C
Vergote
G
G
Bortel
L Van
LV
Remon
J P
JP
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D002939:Ciprofloxacin / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004008:Diclofenac / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D004355:Drug Stability; D004356:Drug Storage; D006358:Hot Temperature; D006801:Humans; D006813:Humidity; D008297:Male; D012995:Solubility; D013607:Tablets; D013696:Temperature; D013810:Therapeutic Equivalency; D013997:Time Factors; D014329:Tropical Climate
D013607:Tablets; D004008:Diclofenac; D002939:Ciprofloxacin