A new process developed by RP Scherer promises to overcome the stability problems that can occur when certain pharmaceutical actives are formulated alongside fatty acids in softgel capsules.
A number of drugs - including the cholesterol-lowering medication fenofibrate and malaria treatment halofantrine - are formulated in the presence of fatty acids such as oleic acid to improve their absorption. For example, long-chain fatty acids are taken up in the lymphatic system, and so are added to formulations in which the lymph is the desired target site for the active ingredient.
However, one of the problems associated with the formulations containing fatty acids is that chemical instability can arise due to their acidic nature and the presence of reactive carboxyl groups, notes the patent.
In the past, this problem has been solved by refrigerating the capsules to reduce the rate of reaction between the drug and fatty acids, but this can mean that complex storage regimens are required throughout the supply chain. Also, if the drug is not sufficiently soluble in the formulation, cold storage methods result in crystallisation and this means that the capsules must be left at room temperature for a period before consumption to re-dissolve the drug.
RP Scherer's solution, which has just been patented in the US (No 6,652,880) is to dissolve the drug in a liquid vehicle based on a glyceride of a long-chain fatty acid, in which the fatty acids are esterified with glycerol to form a neutral compound which is less reactive, along with a surfactant to disperse the oil in the body.
The process results in a much more stable formulation, according to the patent, and is particularly suitable for oral formulations containing testosterone undecanoate, used for male hormone replacement therapy.
RP Scherer has conducted stability testing that reveals that a formulation of testosterone undecanoate based on this formulation has a longer shelf-life than a conventional formulation based on oleic acid.