Een arts vraagt of het mogelijk is om amitryptilinehydrochloride en flupentixoldihydrochloride te verwerken in een drinkbare vorm?

1. The stability of amitriptyline hydrochloride in aqueous solution by J. Buckles, V. Walters
   

   ABSTRACT Very little information has appeared in the literature concerning the stability of amitriptyline hydrochloride (Fig. 1) either as the solid or in solution. The B.P. 1973 and The Extra Pharmacopoeia (1972) state that amitriptyline hydrochloride should be kept in a well closed container, but give no other storage directions either for the solid or for amitriptyline injection. However, the fact that there is a limit test for ketone and also that the injection is required to be sterilized by filtration would indicate that the solution is subject to decomposition. The present work, using thin layer chromatography and polarography, reports that solutions of amitriptyline hydrochloride in purified water at room temperature are stable for at least 8 weeks if protected from light.

2. Stability of amitriptyline hydrochloride in a commercial aqueous solution by R. Roman, E. M. Cohen, M. E. Christy, W. B. Hagerman

   ABSTRACT A commercial amitriptyline hydrochloride solution was stored at 80° for up to 3 months. High-performance liquid chromatography showed no evidence of amitriptyline hydrochloride degradation. The method also indicated that two reported degradates, 3-(propa-1,3-dienyl)-1,2:4,5-dibenzocyclohepta-1,4-diene and dibenzosuberone, were present at levels less than 0.1% (the detection limit of the method) under the storage conditions. The stability of the commercial solutions is attributed to their relatively low ratio of headspace oxygen to amitriptyline hydrochloride.

3. Flupenthixol dihydrochloride decomposition in aqueous solution. Enever, RP. Li Wan Po, A. Shotton, E. Dept. of Pharm., School of Pharm., Univ. of London, London, WC1N 1AX, England.

   ABSTRACT Flupentixol (flupenthixol) dihydrochloride (I) was studied in aqueous solution in order to identify its decomposition products, to establish the degradation pathway and to examine factors influencing the appearance rate of the main decomposition products. I was oxidized in the presence of air to trifluoromethylthioxanthone, ethanol (alcohols, ethyl) and piperazine via aldehydic and epoxidic intermediates. The formation rate of trifluoromethylthioxanthone increased with increases in pH and oxygen concentration. Buffer ions also affected the decomposition rate. Micelle formation by I protected it from oxidative decomposition.

Besluit
Beide producten zijn blijkbaar zeer goed oplosbaar in water zodat indien de gewenste concentratie het toelaat een dubbele extractie met warm water kan worden overwogen. In het filtraat kan sorbitol worden opgelost. Veel sorbitol (of suiker zoals in suikerstroop) vermindert het zuurstofgehalte. Daarnaast zullen vermoedelijk smaakstoffen moeten worden toegevoegd.
Op gebied van stabiliteit zal amitriptyline niet het hoofdprobleem vormen maar flupenthixol lijkt minder stabiel en onderhevig aan oxidatie. De algemene regel is dat in zuur midden de oxidatie afgeremd wordt. Om een zure pH in te stellen is vitamine C (0.2%) misschien het meest geschikt daar het ook als antoxidant kan fungeren samen met Na2EDTA 0.1%.
Een voorbeeld van een analoge drank (maar zonder vitamine C en EDTA) vinden we voor fluoxetine :

R/ Fluoxetine HCl 400mg
Gezuiverd water 30g
Nabenzoaat 100mg
Glycerol 20g
Muntspiritus 1g
Sorbitoloplossing 70% tot 100ml