Stability of Oral Oxytocics in Tropical Climates - Results of Simulation Studies on Oral Ergometrine, Oral Methylergometrine, Buccal Oxytocin and Buccal Desamino-Oxytocin - EDM Research Series No. 012
(1994; 52 pages) Voir le document au format PDF
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Ouvrir ce répertoire et afficher son contenuIntroduction
Ouvrir ce répertoire et afficher son contenuMaterials and methods
Ouvrir ce répertoire et afficher son contenuResults
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Afficher le documentMaterials and methods
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Ouvrir ce répertoire et afficher son contenuAnnexes
 

Materials and methods

Simulated tropical conditions

The methods in the protocol "Protocol of the research of the stability of drugs in aqueous solutions" by the Dutch Society of Hospital Pharmacists (19) were adapted and used to serve the objectives of the study. Tropical conditions were simulated, paying attention to the effect of humidity, temperature and light on the concentration of the active ingredient (Table II).

Definitions of these simulated tropical conditions were derived from data from the literature (16,17,28). Hartmann (17) has formulated generally accepted test conditions (calculated storage conditions) to "define" a climatic zone. From these data and data from Bos (8) we defined our calculated storage conditions (Table V), which formed the base for the simulated tropical conditions that were actually used (Table II).

Table V: Calculated storage conditions for worldwide stability testing

Temperature °C

Relative humidity (RH %)

Intended for:

4°C

ambient

refrigerator

20°C

60-65%

temperate climate

30°C

<65% >65%

hot and dry climate hot and humid climate

40°C

<40%

recognition of critical quality characteristics, special storage instructions

50°C

<20%

recognition of critical quality characteristics (short-term experiments)

Materials

Drug stability is dependent on many product-related factors (29,30), i.e. the active ingredient, the excipients, the dosage form, the manufacturing process and the nature of the packaging. We chose those manufacturers whose products are actually most widely available in developing countries. ME has been included in our investigation because of the claims that it shows less hypertensive side-effects and less influence on postpartum prolactin levels (31,32). It is as cheap as E. The choice of the manufacturer was based on availability. Although E and ME are being produced on "market demand", in practice they are produced only once a year. More than one freshly produced batch from different manufacturers was therefore unavailable. Comparison between different brands has therefore not been possible in this study, as Hogerzeil et al (13) had recommended.

Buccal OT tablets have been withdrawn from the market, as greater control was achieved by intravenous or intramuscular administrations of oxytocin, and because buccal absorption had been unpredictable (33). Despite unfavourable pharmacokinetic data (33-37), we still considered it useful to examine whether buccal oxytocin would be an acceptable, non-parenteral prophylactic oxytocic. The pharmacokinetic studies mentioned had been small and not fully convincing in discouraging its use as an alternative non-parenteral oxytocic for active management of the third stage of labour. As buccal oxytocin tablets have been withdrawn from the market, we were fortunate to be able to import samples of OT and DOT. Because the products are no longer manufactured, we could obtain just one brand of both.

Degradation of active ingredient

To assess their stability under tropical climates, we examined tablets for content of active ingredient (29,30). The efficacy of a product may decrease over time, due to degradation of the active ingredient. Loss of potency usually results from a chemical change (38,39). In this study attention was mainly paid to chemical stability.

Sampling points in time

Long-term stability studies in "temperate climate" conditions normally last for five years (17). The tablets in this study were subjected to more extreme conditions. A shorter period of investigation was accepted, as deterioration of tablet quality would probably appear sooner. Therefore, the stability test was performed for a period of only one year. It was assumed that no additional information would be obtained from longer testing, and in any case such tablets are normally used within a year in tropical countries.

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