Materials
Ammonium acetate (high-performance liquid chromatography (HPLC) grade), 37% hydrochloric acid, sodium hydroxide, sodium chloride, glacial acetic acid, potassium dihydrogen phosphate, acetonitrile (HPLC grade) and methanol (HPLC grade) were purchased from Fisher Scientific (UK). Trifluoroacetic acid (TFA) (HPLC grade), montelukast sodium (pharmaceutical secondary standard) and mesalazine (≥ 99%) were obtained from Sigma-Aldrich Company Ltd. (UK). Water was ultra-pure (Milli-Q) laboratory grade. Regenerated cellulose (RC) membrane filters (0.45 μm) (Cronus®, UK), and filter papers (0.45 μm), polytetrafluoroethylene (PTFE) filters (0.45 μm) and glass microfiber (GF/D) filters (2.7 μm) (Whatman®, UK) were used. Porous full flow polyethylene cannula filters (10 μm) were obtained from Quality Lab Accessories LCC (USA). Nine different soft foods and drinks were used as co-administration vehicles. These were chosen based on differences in their composition, physicochemical properties and drug solubility in each vehicle; these factors are extensively described in our previous study (11). Orange squash, milk U.H.T. full fat and orange juice were purchased from The Co-Operative (UK). Blackcurrant squash was from Lucozade Ribena Suntory Ltd. (UK). First Infant Milk (cow’s milk-based formula) was from Cow & Gate (UK). Applesauces were Bramley applesauce Colman’s of Norwich (referred to as ‘applesauce UK’) from Unilever (UK) and Apfelmark applesauce (referred to as ‘applesauce DE’) from Bauck Hof (Germany). Plain yoghurt from Yeo Valley (UK) and Greek yoghurt from Fage (Greece) were also used. The four formulations studied were kindly donated by AstraZeneca (UK). Product information is summarised in Table I.
Table I Information of the Formulations Used in This Study
Active principal ingredient (API) Brand Manufacturer Formulation type/release mechanism Excipients Dose tested (mg) Administration recommendations (26)
Mesalazine Salofalk® Dr. Falk Pharma (UK) Granules/delayed release pH-dependent Aspartame (E 951), carmellose sodium, cellulose, citric acid, silica, hypromellose, magnesium stearate, Eudragit L 100, Eudragit NE 40 D containing 2% nonoxynol 100, povidone K 25, simeticone, sorbic acid, talc, titanium dioxide (E 171), triethyl citrate, vanilla custard flavour 135 Granules should be placed on the tongue and washed down with water without chewing.
Pentasa® Ferring (UK) Granules/extended release pH-independent coating Ethylcellulose, povidone 135 Granules should be placed on the tongue and washed down with water or orange juice, without chewing. Contents of one sachet should be weighed and divided immediately before use; any remaining granules should be discarded.
Montelukast Singulair® Merck Sharp & Dohme Ltd. (UK) Granules/immediate release Mannitol, hydroxy-propyl cellulose, magnesium stearate 4 Granules may be swallowed or mixed with cold, soft foods (not liquid), and taken immediately.
Actavis® Actavis (UK) Chewable tablets/immediate release Lactose monohydrate, aspartame 5 Tablet should not be taken with food; should be taken at least 1 h before or 2 h after food.