(1994; 52 pages)
Background of the project
Postpartum haemorrhage (PPH) is still one of the most common causes of maternal death, especially in third world countries (1,2,3). In these countries emergency referral in cases of severe bleeding is difficult to arrange, so its prevention and management at all levels of obstetric care is vital. For prevention and management of PPH, the use of oxytocics in the postpartum period is advocated (4). Oxytocin is the preferred drug in the prevention and management of blood loss after childbirth (3,5). In tropical climates drugs need to be stable, and when they are used by untrained people the route of administration should be simple. Therefore, the use of oral oxytocic drugs [oral ergometrine (E), methylergometrine (ME), buccal oxytocin (OT) and buccal desamino-oxytocin (DOT)], with a favourable effect on both blood loss and maternal morbidity and mortality, was regarded as a possible solution to these problems in tropical countries.
The stability of preparations under tropical conditions is not normally investigated during manufacturers' stability studies; and if it is, the results are not readily available. In third world countries, it is often practically and/or economically impossible to protect pharmaceutical preparations from the harmful effects of high temperatures and high relative humidity during transportation, storage and use. Protection against the heat is only possible by storing products in cooled storage rooms or refrigerators. More often than not, this is impossible (6,7). Use of humidity-resistant packaging, which could protect the drug until the moment of consumption, is too expensive for general use in developing countries (up to one third of the price of the unpacked drug) (8). Thus, as soon as a sealed container is opened, humidity can penetrate and accelerate physical, chemical, as well as microbiological deterioration and affect the stability of the drug.
Recent reports and stability studies of injectable oxytocics have shown a remarkable degree of instability on exposure to increased temperatures and exposure to light (9-12); injectable E and ME, in particular, are unstable under (simulated) tropical conditions. Moreover, large differences in potency and stability between the various brands and formulations seem to be more important than the differences between ergometrine and methylergometrine. Under tropical conditions, injectable oxytocin is more stable than injectable (methyl)ergometrine (13).
Almost nothing is known about the stability of ergometrine, methylergometrine or oxytocin tablets under tropical conditions. Recommendations for storage of ergometrine and methylergometrine tablets all advise the use of well-sealed containers for ergometrine tablets and tight, light resistant containers for methylergometrine tablets. General storage temperature recommendations indicate storage at a temperature not exceeding 8°C (6,9,14) and not exceeding 25°C for oxytocin (15). We assumed that the stability of tablets would be better than the stability of ampoules. The absence of stability data on tablets in both temperate and tropical climates meant that a stability study of oxytocic tablets under (simulated) tropical conditions was needed.
The aim of the investigation was to examine the stability of ergometrine, methyl-ergometrine, oxytocin and desamino-oxytocin tablets, in order to determine whether it would be feasible to replace the parenteral route of oxytocics by these drugs. The stability of the compounds was assessed by an experimental shelf-life methodology.